This is a round-up of the TAWOP news items from 2008 through to 2011. Time moves on and so some of the items will no longer be relevant. For instance some health policies have been superceded and some promising drugs have failed clinical trials. However if you read through sequentially the story should emerge as this piece starts with 2008 news stories and moves through to 2011. References are given at the end of the article and there is also a list of open-access and other resources for further reading.
2008
2008 was a great year for psychiatry related research! Here are some of the studies covered earlier on this blog.
Research into Dementia
There are many theories of how different forms of dementia arise and more are being developed. Alzforum provides a useful overview of current hypotheses. There were a number of theories covered in the blog. A potential marker of glial cell activity was identified in one study which found increased uptake of the compound [11C]DAA1106 in people with Alzheimer’s Disease suggesting that glial cell activity might be increased. There was some indirect evidence for a more protective role of the Val-Met form of Brain derived Neurotrophic Factor compared to the Val-Val form. The association of polyunsaturated fats and the healthy aging brain were reviewed in one paper. Gingival bleeding was associated with reduced performance on the Serial Digit Learning Test and loss of periodontal attachment was associated with impairment in the Symbol Digit Substitution Test in the NHANES III Community sample of 5138 participants aged 20 to 59 years old. Perhaps dental health over a long time period may be of relevance to dementia although the evidence should ideally come from longitudinal studies. A variant of the KIBRA gene has been associated with risk of Alzheimer’s Disease and episodic memory. In Nature there was a discussion of a gene for regulating Calcium that has been implicated in Alzheimer’s Disease. Vascular resistance was associated with vascular dementia but not Alzheimer’s in another study. Sarkar and Rubisztein review the process of autophagy, whereby a cell breaks down its own constituents and review a number of promising related agents that may be useful in neurodegenerative disorders. Evidence for predictors of Alzheimer’s Disease affecting cognitive performance in childhood has been found in one study. An association between the nicotinic acetylcholine receptor (CHRNA7 – T allele of rs6494223) and delusions in Alzheimer’s Disease is suggested by research published in Neuromolecular Medicine. A post-mortem of 124 people with diabetes found there were less neuritic plaques if they had been taking insulin together with their medications. The authors of a post-mortem study in people with Huntington’s Disease found a significant reduction in hypocretin-1 neurons compared to controls in the prefrontal cortex and CSF although the clinical significance is unclear. The findings in a study of Rem Sleep Behavioural Disorder in Parkinson’s Disease suggest that this may be a sub-type of Parkinson’s Disease. They found that if the sleep disorder occurred, then the tremor was less marked in the Parkinson’s Disease, that people were less responsive to the medication and had a higher frequency of falls. The rate at which the brain atrophies has been associated with cognitive decline and also with the risk of progressing to dementia. ‘Theory of mind’ has been found to be impaired in Alzheimer’s Disease and Frontotemporal Dementia relative to healthy controls with an evidence base building up for the relationship with dementia.
There were a few drug trials covered, looking from different perspectives. Thus in the prospective Rotterdam study involving 6992 subjects, taking statins was associated with a significant reduction in the risk of Alzheimer’s Disease – the Hazards Ratio was 0.57 with a 95% confidence interval of 0.37-0.90. A 16-week double-blind placebo-controlled trial of Galantamine in 69 people with Parkinson’s Disease without dementia found no improvement on a number of cognitive, behavioural or motor outcomes although there was a statistically significant drop-out due to GI side-effects and worsening Parkinson’s Disease symptoms. The relationship between anticholinesterase inhibitors and circadian rhythms was reviewed in one paper. Administration of Memantine to women at risk of Alzheimer’s impaired memory and verbal learning while improving executive functioning.
A few studies looking at different aspects of service delivery were also covered. Thus the delivery of a telephone-based service for carers of people with dementia was found to lead to significant improvements in caregiver burden scores. The authors of a systematic review of common activities of daily living scales used in dementia conclude that further data on their psychometric properties is needed to justify their widespread use. Krinsky-McHale and colleagues published the results of a new test which can help in the early identification of Alzheimer’s disease in people with Down’s syndrome.
Studies building on established knowledge were covered. Thus doubling times for the incidence of Alzheimer’s Disease was found to be approximately 5 years in one recent study which showed no significant geographic difference in these doubling times. A study of 3303 brains has shown that in 53% of cases, dementia consists of mixed pathology. The authors conclude that synucleopathies uncommonly occur alone. A recent post-mortem study of 524 people who had dementia showed a breakdown of Alzheimer’s Disease – 42%, vascular dementia – 24%, combined Alzheimer’s and vascular – 22% and fronto-temporal dementia – 4%. 123I-FP-CIT SPECT scanning was found to have 78.6% sensitivity and 87.9% specificity in differentiating between Alzheimer’s Disease and Lewy Body Dementia.
Mild cognitive impairment is an area of increasing research activity and a number of papers were covered. In a study of 1969 people (329 with MCI) the group with MCI were found to have an OR of 8.12 for delusions (95% CI 2.92-22.60) which however were rare in both groups. Apathy was more common in both groups with an OR of 4.53 although interestingly the OR for depression was 2.78. A paradox which needs explaining is the finding that the risk of MCI conversion to dementia decreases as time progresses. In another study there was a finding that nearly half of cases of vascular cognitive impairment non-dementia resolved spontaneously. In a post-mortem study (open-access article) of people with Alzheimer’s Disease or mild cognitive impairment, the authors concluded that when the disease is widespread that agreement between pathologists is good but in the initial stages of the disease there is a need for standardisation of the sampling method and also a need for two pathologists to confirm the results. 45% of people with vascular cognitive-impairment non-dementia reverted in this 1-year follow-up study. A phase II trial of AL-108 in mild cognitive impairment showed an improvement in memory whilst a combination of oral diabetes drugs and insulin results in less amyloid plaques (which accumulate in Alzheimer’s Disease) in the brain.
Predictors of conversion from mild cognitive impairment to Alzheimer’s Disease including MRI Hippocampal and Entorhinal Cortex volumes as well as performance on a smell test (UPSIT) and selective reminding test (SRT). Developing this theme further, there have been a number of studies reinforcing the importance of the hippocampus in memory and also looking at factors which may influence hippocampal volume. Thus Hippocampal volume has been found to be predictive of memory performance in aging pilots. Being an ApoE4 carrier also had some predictive value. An MRI study of hippocampal volume in medical doctors and controls with no tertiary education found no significant difference between the doctors and the control group. Length of time in medical practice also had no effect on volume. The authors conclude that as there is an effect for taxi drivers, hippocampal volume is most likely to increase in volume in response to a need for large scale spatial mapping. A study of 21 women has found that there are variations in hippocampal volume with the menstrual cycle, with an increase in anterior hippocampal volume and decrease in right dorsal basal ganglia volumes after menstruation, as well as an improvement in verbal declarative memory during this time. A link has been suggested between vascular endothelial growth factor and the size of the hippocampus. There is a special issue of Hippocampus dedicated to grid cells. These are special types of cells in the Entorhinal Cortex similar to place cells except that they code for a larger part of the environment.
There were also a number of studies that looked at the molecular biology of plaque formation including plaque precursors covered. A new in vivo screening process for compounds which interfere with the development of ABeta plaques was developed and involved the use of folate. There is evidence for Amyloid deposition in Lewy Body Dementia but very low levels in Parkinson’s Disease(PDD) or PDD+. ABeta42 levels were found to be lowest in people with Lewy Body Dementia compared to other types of dementia in one study but highest in Alzheimer’s Disease. In a study of 35 older adults, serum Beta-Amyloid levels were correlated with worse peformance on cognitive testing.
In a study of apathy (measure using the Apathy Evaluation Scale) in people with dementia, apathy was more likely if the person was living with someone other than their spouse and was also associated with irritability and functional impairment. Executive dysfunction predicted functional abilities in the elderly with cognitive impairment in one study.
Research into Psychosis
Prediction of developing schizophrenia from those at high risk was the focus for a number of studies. Thus Ultra-high risk of conversion to schizophrenia was associated with metabolic processing in the corpus callosum and in another study with the structure of the anterior cingulate cortex. A study published in the journal Psychological Medicine looking at 900,000 schoolchildren found that those who received an E grade had a higher risk of developing schizophrenia. This suggests that in some people who are having difficulties with exams this may be an early sign of developing a psychotic illness. A cautionary note however is that this finding is non-specific. People may have difficulties with exams for a number of reasons and people who do well at school may go on to develop psychosis. Enuresis in childhood has been associated with later development of schizophrenia – although it should be emphasised this is an association study and not causal. There was also some evidence of childhood bullying leading to an increased likelihood of psychosis. In this cohort study of 6872 people, there was found to be a 4 fold increase in prevalence of schizophrenia spectrum disorders with maternal haemoglobin concentrations less than 10gm/dl and the authors recommend further studies to confirm the relationship. The results of one study suggest that If mothers in second month of pregnancy during the six day war they were 4.2 more likely to have children with schizophrenia than mother’s pregnant at other times. The authors of a case study found an association between schizophrenia and middle ear disease.
There were various studies looking at cultural aspects of psychosis and related conditions from many different perspectives. A study of unmet need in East Timor looked at 1544 people in urban and rural areas and found a DSM-IV point prevalence of 1.35% for psychosis and 1.47% for PTSD and that psychosis was usually treated by traditional healers. There was found to be a significant inverse relationship between Gross Domestic Product and duration of untreated psychosis in this study in the British Journal of Psychiatry. A chinese study of 137 families with 2 or more members with schizophrenia showed significant familial aggregation in a number of categories including the DSM-IV categories of schizophrenia and positive symptoms. ‘The Truman Show’ delusion was reported on in this article – based on case studies where people believe their lives are similar to the character from the Truman show. In this film, Jim Carrey’s character is living in a television program and provides the ‘entertainment’ for television viewers following his life (unbeknown to him!). Occurrence of paranoid ideation in a group of healthy volunteers from Iran was comparable with results from Europe.
A number of drug trials looked at different aspects of treatment ranging from receptor occupancy to various neuropsychological outcomes. A SPECT study in 46 people with schizophrenia looked at striatal D2 receptor occupancy rates in the case of four antipsychotics. They found the following upper limits for receptor occupancy: Risperidone – 75%, Olanzapine – 84%, Clozapine – 53% and Quetiapine – 64%. In a study of 15 people with schizophrenia, a benzodiazepine-like compound acting at the GABAa receptor was found to improve markers of prefrontal cortical function including performance on the N-back task (an open source game based on this task is freely available here) and in EEG gamma oscillations during preparation for tasks. A complex relationship has been found between the dosage of an antipsychotic and adherence to medication, with adherence varying according to time after initiation of medication and also between antipsychotics. A study funded by a number of pharmaceutical companies and presented in an open-access paper has found that a partial dopaminergic agonist Bifupronex (20mg) significantly reduced total PANSS scores in people with schizophrenia compared with a placebo group in this 6/52 double-blind placebo-controlled trial. In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial, estimated 10-year risk for CHD was compared in 1125 people followed who had been followed for 18 months. There was found to be a significant increase for the Olanzapine group of 0.5% (SE 0.3) and for Quetiapine of 0.3% (SE 0.3). The risk was decreased for perphenazine -0.5% (SE 0.3), Risperidone -0.6% (SE 0.3) and Ziprasidone -0.6% (SE 0.4). A study of 33 people with schizophrenia looked at smooth pursuit eye movements before treatment (patients were drug naive) and after treatment with olanzapine or risperidone. After treatment there was found to be a reduction in the gain of the eye movements which the authors speculate is related to serotonin’s role in sensorimotor processing. In a very interesting study in which medications were donated by a number of different pharmaceutical companies, there was found to be no difference in incidence of EPSE’s or in scores of EPSE’s between groups treated with first or second generation antipsychotics. There were a number of findings in the secondary analysis for individual antipsychotics.
There have also been studies examing neurodevelopmental and neurodegenerative models of schizophrenia. There have also been a number of very specific hypotheses with evidence to support them. In a study of twin pairs, the healthy twin of a sibling with schizophrenia was found to have greater whole brain volume reduction and frontal/temporal gray matter volume reduction over 5-years compared to twin pairs without schizophrenia. There is an article on neurodevelopment in childhood-onset schizophrenia showing a 2% slower rate of growth in the right hemisphere compared to controls. This is interesting in the context of a theory proposed by Crow. The authors of another paper in the BJPsych found that motor coordination and neurological signs were found more frequently in people presenting with first episode psychosis compared with controls and when controlling for IQ. Changes in the white matter tracts near the left fronto-occipital fasciculus have been found in association with psychosis. Such a specific hypothesis is ‘relatively’ easy to test and replications of such studies will be awaited with interest. In a study in the British Journal of Psychiatry there was found to be an association between lower IQ and psychotic symptoms (bear in mind that we are talking about symptoms rather than a diagnosis e.g. schizophrenia) The full article is available here. A study found ‘Theory of Mind’ deficits in Schizophrenia but also found that the patterns of these deficits differed from one person to another. Evidence was found for changes in the expression of genes for sphingolipid/glycolipid metabolism in people with schizophrenia.
There were also a number of studies looking at neuropsychological function, adding to the already extensive evidence base in this area. Interventions including prompting recall of events and looking at identity improved autobiographical memory in people with schizophrenia. In a study of 119 people with first-episode psychosis (plus 107 controls) there was found to be an impairment in reinforcement and reversal learning (learning different responses for two stimuli and then reversing the responses). There was not a significant difference between the affective and non-affective psychosis groups. There was a significant association between reinforcement learning and negative symptoms however. One study showed a relationship between self-referential source memory (keeping track of one’s own responses) and social cognition in people with schizophrenia. In first episode psychosis, processing speed was found to be significantly reduced compared to controls and this was related to working memory problems and prognosis at one year. There was found to be a relationship between lissencephaly genes and executive dysfunction in schizophrenia and bipolar disorder. This might be signal a trend towards relating genes to components of an illness (e.g. executive function, memory etc), where these components come together produce an illness and would fit with the evidence suggesting the involvement of many genes.
Longer term outcomes including relapse were also covered. In a 2-year follow-up of first episode psychosis, concurrent substance misuse was the most significant predictor of relapse. Another study in the BJPsych found that a longer the period of untreated psychosis predicted poor social outcome.
One article suggested a trend towards OCD occuring prior to schizophrenia when it was a comorbidity although the authors suggest a need for further research to examine this relationship. In another study, people with schizophrenia were found to be less likely to receive treatment for medical conditions. An Australian study has found no difference between CBT for psychosis and treatment as usual in a group of 94 people with psychosis randomised to either group. The authors give a number of reasons why this might be so.
Research into Depression
In a Romanian study involving 170 subjects there was found to be no difference in effect on Beck Depression Inventory scores for Fluoxetine, Cognitive Therapy and Rational Emotive Behavioural Therapy. However the latter two were found to be more cost-effective. There was an open-label study of Citalopram in 54 people with traumatic brain injury (tbi) and major depressive disorder (mdd) treated for 6 weeks or 26 people (with tbi and mdd) treated for 6 weeks. The authors found that at 10 weeks, 26.9% of people were in remission and that the results were less than previous studies in people with tbi but equivalent to results in the general population. However it should be noted that there is no placebo group although this does reflect real world practice where both the patient and doctor know which treatment is being prescribed. The authors of a meta-analysis concluded that there was a 67.1% response rate for Mirtazapine and 62.1% response rate for SSRI’s with different side-effect profiles for each. A hydrolysed protein form of the tryptophan diet was found to have an advantage in effect on mood compared to other tryptophan diets or placebo. A cohort study (1946 British Cohort) found that 10 years after taking antidepressants, people were less likely to experience a mental disorder although the odds ratio of 0.3 had a 95% Confidence Interval of 0.1-1. Interestingly only a quarter of people were still taking antidepressants. In this randomised double-blind augmentation study in major depressive disorder, Fluoxetine plus Quetiapine achieved a more rapid improvement in insomnia but not a more rapid improvement in depression scores compared to fluoxetine alone. Quality of life improved in a large randomised double-blind placebo controlled trial of escitalopram in major depressive disorder or generalised anxiety disorder. However quality of life scores approached that of a community sample in remission in major depression but was less in generalised anxiety disorder. An intriguing application of N-Acetylcysteine, which is used in the treatment of paracetamol overdose, has been found to have some benefit in depression. N-Acetylcysteine is a precursor of Glutathione which is used in various cellular processes. Other research has found a reduction of Glutathione in depression although the relationship is probably far from straightforward
There have been a number of studies looking at neuroanatomical changes in depression. There was found to be a reduction in Anterior Cingulate Cortex volume in people with depression in a recent study and there was evidence that this was mediated both by depression and short term treatment. The Right Anterior Insula was activated in people with depression when anticipating painful stimuli in one study (together with the Anterior Cingulate Cortex and the Right Amygdala) perhaps suggesting a reduced ability to modify emotional responses in depression. In this prospective study of 38 patients with major depression (30 controls) there was found to be a significant reduction in grey matter volume in the hippocampus, right dorsomedial prefrontal cortex, left amygdala and anterior cingulum. There were also found to be differences in the grey matter volume changes between remitters and non-remitters
There were also some studies looking at predictive models of depression. A new scale for measuring ruminative thought – the ruminative thought style questionnaire has been developed to reduce bias from depressive symptoms. This has been found to differ from the standard measure the Response Style Questionnaire in both the constructs being measured and also displaying improved prediction of future depression. The Health in Men study found a correlation between Homocysteine levels and risk of depression. A meta-analysis published in the Journal of the American Academy of Child and Adolescent Psychiatry shows an increased prevalence of depression in adolescent girls in young offenders units (29% aged 10-19). Young people in offenders units are at risk of many different mental illnesses. A study of 800 children found that those of low birth weight were more likely to develop anxiety and depression.
There were also a number of studies looking at the relationship between cardiovascular (or related) disease and depression. Licht and colleagues found decreased heart rate variability in 774 people with major depression in remission, 1075 with current major depression versus 524 controls in the Netherlands Study of Depression and Anxiety and that this was correlated with use of antidepressants. Vogelzangs and colleagues in a study of 2088 people, found that depression measured at baseline was significantly associated with increased visceral fat and sagittal diameter at 5 years. There was found to be an association between major depressive disorder and CRP as well as a relationship between major depressive disorder and ischaemic heart disease which was independent of CRP in the EPIC-Norfolk study. In the Baltimore Longitudinal Study there was found to be no relationship between depression and carotid intimal media thickness in 566 participants examined between 1 and 15 years after inclusion (age 20-93 years).
Overcrowding on wards was associated with staff’s use of antidepressants in another study. One study in the Archives of General Psychiatry has shown that levels of the serotonin transport protein in the brain changes with the seasons particularly in the autumn and winter suggesting a mechanism that may account for seasonal affective disorder. The authors of a meta-analysis of 103 papers looking at computerised CBT concluded that there was some evidence of effectiveness. Indeed evidence that Beating the Blues was better than the usual treatment for depression was discussed. There are many questions that remain unanswered however (e.g what is the role of the therapist). People with panic disorder have reduced 5-HT1A binding pre and post-synaptically compared to controls using PET scanning and a 5-HT1A tracer. Research in Biological Psychiatry has further validated the concept of vascular depression in the elderly. The research showed remarkable specificity and sensitivity when using deep white matter lesions as criteria.
Research into Bipolar Disorder
An expert consensus meeting concluded that the Bipolar Disorder was more likely to be a neurodegenerative disorder than a neurodevelopmental one for some types of cognition. A study involving 13,500 people with Bipolar Disorder and published in the Archives of General Psychiatry has found that as a father’s age increases so too does his chances of having children with Bipolar Disorder. In a placebo-controlled trial looking at augmentation of Valproate or Lithium with Aripiprazole (15-30mg daily) in the treatment of mania (treatment number = 253, placebo number = 131), the researchers found that there was significant improvement in Young Mania Rating Scale scores after six weeks (-13.3 v -10.7) and that improvement was noticeable after one week. 300 people with Bipolar I disorder (with mania) were randomised into treatment with Lithium or Valproate. The trial was relative short in duration at 12-weeks but non-inferiority of Valproate to Lithium was demonstrated using Young Mania Rating Scale scores. In the Archives of General Psychiatry there is free online access to a NIH funded study on Bipolar Disorder in children. This was an eight year follow-up study of 108 children (initially aged 7-16) showing at follow-up a higher prevalence of mania than the general population assessed using the WASH-U-KSADS. Research into bipolar disorder in children has produced a lot of debate.
Research into PTSD
Research indicates that Uganda has the highest prevalence of Post-Traumatic Stress Disorder in the world – estimated at just over 54%. The study was published in June in BMC Psychiatry. Researchers looked at more than 1200 people in 2006 during which time there was a war in northern Uganda. An alternative diagnostic process to DSM-IV criteria for diagnosing PTSD in children was used in this study and the researchers found that for the age group 7-10 years old, a combination of the child and parent’s report were better able to predicts PTSD, which in this case followed a motor accident. There were some other implications from this study in terms of diagnosis. PTSD was found to influence mortality rates in people who received implantable defibrillators. A study of PTSD in WWII prisoners of war found that higher IQ appeared to be a protective factor against developing PTSD and that PTSD was associated with performance on certain frontal lobe tests
An organisation working with vulnerable children, The Kids Company, are working together with the Institute of Psychiatry on research into the effects of trauma on children. In this article, there is an interesting comment on the funding that goes into supporting families with vulnerable children and the funding of superprisons, posing the question of whether it might be possible to prevent crime rather than manage it when it occurs by diverting resources. A study looking at Venlafaxine Extended release form in PTSD found that it had a variable effect on resilience scores using the Connor Davidson Resilience Scale. The authors recommend the use of such measures in evaluating response in PTSD. A fascinating study has found that people with PTSD are less likely to respond to CBT if they have impairments in verbal memory. An association has been found between an ice storm in Quebec and developmental delay in children born to mothers who were pregnant during the storm. In the journal Child and Adolescent Psychiatry and Mental Health, a study followed up children with juvenile dissociative disorder and found that 83% of the people met criteria for a psychiatric disorder (an average of 12 years later). Furthermore just over 25% still experienced a dissociative disorder.
Research into ADHD
A Magnetic Resonance Spectroscopy study of 31 children with ADHD who had not been treated with psychostimulants and 36 healthy controls found that membrane phospholipid precursor levels in the prefrontal cortex were decreased in the ADHD group and were higher in the inferior parietal region. The authors interpreted this to mean this as a developmental dysfunction in cortico-striato-thalamo-cortical networks .
Research into Anxiety Disorders
A meta-analysis of internet and computer based CBT packages found them to be superior to placebo, waiting list and therapist delivered CBT across a range of anxiety disorders although the authors comment that large scale studies are required to confirm their findings. In another study there was found to be an increased risk of developing a heart attack of 1/3 in those who had panic disorder under the age of 50.
Research into OCD
A small randomised double-blind placebo study in the American Journal of Psychiatry suggests that compared to placebo, Olanzapine leads to higher weight gain and reduction of obsessive symptoms. The authors advise that further trials are warranted to replicate these findings. A comparison of 20 people with trichotillomania and 19 controls revealed increased grey matter changes in the left striatum, amygdala and hippocampus as well as many areas bilaterally.
Research into Personality Disorder
There were a number of large studies looking at Personality Disorder and adding to the knowledge base of these complex diagnostic categories. In a Norwegian twin study involving 2794 members of the Norwegian Institute of Public Health Twin Panel, one of the genetic factors was found to predispose generally to Personality Disorder rather than to specific subtypes while two others related to high impulsivity and introversion. There was also found to be a lower prevalence of borderline personality disorders in Spanish immigrants compared to the indigenous population particularly in Asia and Sub-Saharan people. Three subtypes of Narcissistic Personality Disorder are proposed on the basis of one survey of 1200 clinicians and includes the fragile subtype, malignant/grandiose subtype as well as the high-functioning and exhibitionist subtype. In the National Epidemiologic Study on Alcohol and Related Conditions (n = 43093) there was an association between higher than normal body weight and paranoid, avoidant and antisocial personality disorders in women, being underweight and schizoid personality disorder in women and being underweight and paranoid personality disorder in men. One study reported that prison psychiatric inpatients with tattoos are more likely to have antisocial personality disorder. This study was carried out in prison, where there is a higher prevalence of antisocial personality disorder. This provoked lots of responses including points about tattoos being a cultural phenomenon (e.g. depending on fashion) and also different types of tattoos may vary in their significance. Check out the Shrink Rap Blog for a perspective on this study.
Research in Learning Disability Psychiatry
In one study People with Cornelia de Lange syndrome were found to have a higher rate of severe autistic phenotypes. In a Japanese study of 84 people with high-functioning autism and 208 controls there was found to be a significant association between paternal age and high-functioning autism.
Eating Disorders (and related) Research
Ghrelin and Obestatin secretion was found to be subtly altered in women with anorexia compared to controls. A study involving 3000 children and looking at a variation of the FTO gene, which has been implicated in obesity, has shown that those with the gene were less likely to feel full than those without that variant of the gene. Metabolic syndrome was associated with individual and neighbourhood socioeconomic status in women but not men. In an analysis of the Rotterdam study it was found that total cholesterol was positively correlated with sleep duration.
Liaison Psychiatry
In a study of 193 people admitted to hospital with coronary artery disease perceptions of serious consequences of CAD were found to influence adherence. One of the strongest predictors was ‘social desirability’. The World Mental Health Survey which included 18 population surveys of households in 17 countries using the World Mental Health-Composite International Diagnostic Interview (WMH-CIDI) found that people with Rheumatoid Arthritis had an OR of 1.9 for mood and anxiety disorders and 1.5 for alcohol abuse/dependence when compared to people without Rheumatoid Arthritis. A study by Christodolou and colleagues characterised people who were transferred from medical/surgical beds to a psychiatric ward finding higher rates of mood disorders and specific demographics such as being single, living alone and belonging to a lower socioeconomic class. A meta-analysis of non-pharmacological treatments for cancer-related fatigue has found that both exercise and a range of psychological interventions are roughly similar in their benefits.
Substance Misuse
A study looking at 40 men drinking beer in a bar found that louder music made them drink more quickly. Research has found a specific alteration of the immune response in people with alcohol dependence. The researchers found that the neutrophil’s ‘respiratory burst’ was reduced. When neutrophils ‘consume’ bacteria or foreign particles, they are thought to destroy them using this respiratory burst which involves the action of powerful enzymes such as Superoxide Dismutase. Other research has begun to identify some of the brain changes that might occur in Foetal Alcohol Spectrum Disorder (FASD). A survey of 289 members of Alcoholics Anonymous found an increase rate of smoking and that smokers reported that it impacted on their mood. An analysis of UK Radio DJ’s comments on alcohol reveals a tendency towards encouraging alcohol use. There was found to be evidence for reduced prefrontal cortical thickness in cocaine dependence which was correlated with reduced behavioural repertoire. There was also reduced cortical thickness heterogeneity and evidence of a neuroanatomical differences that may contribute to predisposition to dependence. A study looking at smokers and non-smokers associated the pleasurable feeling of smoking and going on to become a smoker with a variation in the nicotine receptor CHRNA5 (having the less common rs16969968 variant).
Child and Adolescent Psychiatry
A difference in a mother’s brain activation when responding to a newborn’s cry has been found between mothers who underwent caesarean-section versus natural birth. The general conclusion drawn by the authors is that natural birth mothers are more sensitive to their baby crying. However there are a number of assumptions between the activation findings and the general conclusion and there were a very small number of mothers (12) who took part in the study. Further studies with larger numbers are required to draw firmer conclusions. Nevertheless there have been suggestions of a link with Oxytocin. In a study of 1970 children there was found to be a significant association between high or chronic levels of peer victimisation (using various measures) and parenting behaviours, parental income and physical aggression in children. Research has shown that the amount of REM sleep children and adolescents get can determine their likelihood to develop obesity.
The American Psychiatric Association has called on NBC to pull a program ‘The Baby Borrowers’ in which babies are looked after by another family for three days. Dr Richard Martini, an american Child and Adolescent Psychiatrist has suggested that the new Batman film, The Dark Knight, shouldn’t be watched by children under 10. His argument was that children find it difficult to differentiate between fantasy and reality and that the content was therefore unsuitable.
A study of 100 children who were exposed to irradiation prenatally from the Chernobyl nuclear reactor revealed differences between these children and 50 controls (classmates) including left brain neurological findings, lower IQ and a number of EEG finding. In Ireland, official figures released, show that 3600 children are awaiting assessment by a psychiatrist and of these 1000 children may have to wait more than a year. In the city of Chandigarh in India, a recent study was carried out showing that 25% of adolescents have mental health problems. Professor Arun’s study looked at 2000 children in 10 schools across the city.
Miscellaneous
2008 was the year of the Olympics and Great Britain returned in 4th place. Psychiatrist Dr Steve Peters, the coach for the olympic cycle team which achieved gold in the recent olympics was extensively covered in the news. Another big story, this time from the United States was some research showing that psychiatrists are doing less psychotherapy and more prescribing which was published in the Archives of General Psychiatry. This may reflect a changing role of psychiatrists. In the UK, there was a recent profession-wide statement released about the role of a doctor.
There was much discussion about the controversial topic of internet addiction. The term ‘discomgooglation’ was given to the frustration at being removed from an internet connection. Some recent research has drawn attention to the potential for fruit juices (orange, apple and grapefruit juice) to interact with certain medications. Harrison and Tunbridge argue in a review that the COMT gene may predispose men and women differently to psychiatric illnesses. Rathore and colleagues found in a study of 53,314 people receiving Medicare that those with a mental illness diagnosis had a higher 1-year mortality (41% v 36.2%) .
A National Conference on Depression has been held in Pakistan where it has been reported that there are 400 psychiatrists for each 1.6 million of the population and where alternative methods of treatment for mental illness may be favoured in some parts of the country. Research in Brazil has produced some interesting findings. There are 6000 psychiatrists in the United Healthcare System and three times as many psychologists but only 3119 nurses! In the south-east of the country there are 5 psychiatrists per 100,000 of the population and in the north-east there is only 1 psychiatrist per 100,000. A request by the Indian Psychiatric Association for judges to have psychiatric training has been made.
In the Whitehall II prospective study of 65000 civil servants published in the BMJ and also covered here the researchers found that those who had taken a long period of sick leave were 66% more likely to die early. In the Health Services Journal, Helen Bevan who has experience of over 70 national improvement initiatives writes very positively about the ‘Productive Ward’ covered earlier in the blog. Andrea Greatley commented on media portrayal of mental health issues.
A study has shown that gossip can help to establish reputation and helps people to trust each other. In 768 participants in the Rotterdam Study there was found to be a significant association between duration of sleep and total cholesterol levels which was predicted by length of time in bed and fragmented sleep. Paternal age was associated with impairment in social functioning if the father was less than 20 years old or over 45-years old. A qualitative study of 13 studies of brain injury found that there were no differences in functional outcome between men and women with moderate to severe brain injury. There was a discussion of planar cell polarity genes which determine the morphology of neurons and influence developmental trajectories. There have been a number of cases of transcranial magnetic stimulation being used with some degree of success in coma. In the editorial in Nature Genetics there is discussion of a study in the same issue in which relatively common polymorphisms in structural variants are found to account for much of the variation between individuals in a population. In an fMRI study in people with depersonalisation the researchers found that when processing emotional facial expressions, the depersonalisation group had a quicker haemodynamic response but a lower magnitude of response. This is posited to be the underlying mechanism for depersonalisation. Using medication to augment learning in behavioural therapy is an interesting approach and a meta-analysis of the use of D-cycloserine in exposure therapy has shown benefits for this method. A novel study to look out for is one about near-death experiences. The idea behind the study is that books will be placed on shelves that are only visible from the ceiling. People awaking after operations very occasionally describe these experiences of floating above their body and witnessing the operation.
There was certainly a lot of very interesting research carried out in 2008 and 2009 may be even more interesting yet!
2009
There were a number of interesting studies and reports covered in 2009. These ranged from more results from the STAR*D trial through to the discovery of 3 strong gene candidates in Alzheimer’s Disease, a finding on copy number variants in Schizophrenia and Bipolar Disorder and a recent UK report on the use of antipsychotics in dementia. Big science projects included the revival of an extinct species using cloning, the use of the Diamond Light Synchrotron to investigate iron deposits in the brain, the construction of an 11.7 Tesla MRI scanner in France, the Alzheimer’s Disease Neuroimaging Initiative and a project to make Transmission Electron Microscopic Images available online. There were also developments in the areas of evolutionary psychiatry, discussions around the pending revisions of DSM-IV and ICD-10 and rapid developments in social media which are impacting and have already impacted on culture.
Research in Mood Disorders
A post-mortem study (n=27) compared 17 people who had developed late-life depression with 10 controls and the researchers found a significant reduction in the volume of the pyramidal cells (to a greater extent in layer 5) throughout the cortex in the depression group. Interestingly the layer 5 cells are more susceptible to ischaemic damage which has also been noted to be more prevalent in people with late-life depression suggesting a possible hypothesis which could be explored in future studies (Khundakar et al, 2009).
In a report from the Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D), 2875 people with major depressive disorder receiving citalopram were included in the analysis. 23.5% of participants were identified as having melancholic features and this group was associated with lower remission rates on the Citalopram (absolute reduction of 8.4% relative to the non-melancholic group). After adjustment for clinical features and demographic variables there was no significant difference between the groups. A longitudinal study of 242 people with bipolar disorder with both typical and atypical features showed that there was no difference between the two groups in terms of response to Lithium over a 20-year period on the mean morbidity index. In an american study, 314 psychiatrists were surveyed and 80% reported that they did not use clinical scales in the assessment and treatment of depression and a number of reasons for this were given. Placebo response in paediatric antidepressant trials was found to correlate with the number of sites involved in the study as well as the severity of the depression. The authors found an increasing placebo response (which is similar to a finding reported in an article on dementia research last year) and concluded that this could be due to milder cases of depression being included, increasing numbers of study sites in trials and non-publication of negative studies. There is an interesting editorial by Professor Gordon Parker from the Black Dog Institute in which he looks at some of the reasons why a meta-analysis might produce results different from those seen in clinical practice. This follows on from the 2007 meta-analysis by Kirsch and colleagues. There are some really good points made here amongst which are the sample population in RCT’s (many people with more serious depression may be excluded from trials) as well as expectations of improvement which needs to be compared with pre-morbid functioning. A 12-week double-blind trial (n=485) of Aripiprazole v Haloperidol (5-15mg) in bipolar mania or mixed states found both to be significantly better than placebo in improving Young Mania Rating Scale scores.
In an analysis from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) of 1380 people who met criteria for Bipolar I or II, 2/3 of people with bipolar depression were found to have concurrent manic symptoms and a number of associations with this group were found including earlier age at onset, rapid cycling in past year and bipolar I. In a 10-week trial of 176 adults with bipolar disorder, treatment emergent mania was associated with significantly higher baseline scores on the Young Mania Rating Scale. There was a study looking at complex pharmacology in Bipolar Disorder. 4035 Subjects were recruited from the STAR*D study (just before commencing participation). A receiver operating characteristic analysis was performed (a method which is designed to discriminate between signal and noise). The researchers found that factors such as a high income, taking an atypical antipsychotic , and more than 6 episodes of depression but not age of onset, previous psychosis or hospitalisation were associated with prescription of 4 or more medications (Lithium, anticonvulsant, antidepressant, antipsychotic) (Goldberg et al, 2009). In another STAR*D study a family history of depression didn’t alter remission or response rates but was associated with earlier age of onset of major depressive disorder, longer length of illness and comorbid anxiety (Husain et al, 2009). A potentially important meta-analysis looked at trials of Mirtazapine with comparators/placebo in major depressive disorder and the findings suggested that response in the first two weeks is associated with treatment outcome and in this particular analysis there was a high sensitivity (Szegedi et al, 2009). A longitudinal study looked at 115 people with Bipolar Disorder and examined the relationship between onset of depression and concurrent alcohol use. The researchers concluded that number of days of alcohol use predicted depression when controlling for concurrent substance misuse and current depression (Jaffee et al, 2009). The Maudsley Staging Method for treatment resistant depression has been described in a recent paper where the authors found evidence of face and predictive validity (Fedadu et al, 2009). Using data from the Consortium for Research on Electroconvulsive Therapy (CORE), researchers found that relapse after continuation ECT occurred in 9.8% of people not having had at least 1 antidepressant trial before ECT compared to 34.6% of people who had received at least 1 trial of an antidepressant (Rasmussen et al, 2009). Mirtazapine improved performance on a simulated driving test at 16 and 30 days on measures of road position and crashes (in the simulation) in people with major depressive disorder (28 people with MDD, half of whom received Mirtazapine and the other half were untreated) (Shen et al, 2009).
Migraine with aura was found to be significantly higher in people with depression than in controls with an odds ratio of 5.6 (Samaan et al, 2009). In a study of 45 inpatients with treatment resistant depression, cortisol response was found to be reduced relative to 46 controls and the authors concluded that the HPA axis is set a higher level (i.e. higher cortisol levels)(Juruena et al, 2009). The National Institute of Clinical Excellence has released guidance on the treatment of depression in people with chronic health problems – the quick reference guide is here. A small case series which looked at deep brain stimulation for severe depression provided some evidence of efficacy although given the sample size, it will be interesting to see the outcome of a relevant systematic review or meta-analysis which incorporates this data.
In a study which involved 25 people with bipolar I disorder without a history of psychosis and 24 people with bipolar I disorder with a history of psychosis there weren’t found to be any significant neuropsychological differences between the groups. However the authors concluded that there was a trend towards impaired verbal working memory in the people with a history of psychosis compared to those without which would be consistent with the findings of some research studies in people with schizophrenia. The scores on the Schizotypal Personality Scale were positively correlated with visual recall memory but negatively correlated with verbal memory (Savitz et al, 2009). In a partly GSK-funded study involving 811 people with moderate to severe depression, Nortripytlline and Escitalopram were compared. The graphs showed a close overlap of the two antidepressants on measures of MADRS, HDRS-17 and BDI with time (12 weeks from baseline). However vegetative symptoms (weight loss, appetite, sleep and libido) improved further with Nortriptylline than Escitalopram while the reverse was true for observed mood and cognitive symptoms (Uher et al, 2009). A psychoeducation program which involved 21 90-minute sessions covering awareness of illness, compliance, detection of prodromal symptoms and lifestyle and involved 120 people randomised to the treatment or control groups. Time to recurrence and number of recurrences were significantly less in the psychoeducation group as was the time spent acutely ill (Colom et al, 2009).
A meta-analysis of 14 studies examining aetiology of depression found that variations in the serotonin transporter gene were not associated with an increased risk of depression (This is also covered by the Neurocritic). An Australian study provided further evidence that depression significantly contributes to quality of life measures if people have concurrent somatic and medical conditions but also that dysthymia more significantly impacted on these quality of life measures. A prospective study involving 10,094 subjects over 4 years looked at adherence to a Mediterranean diet and new-onset depression and found evidence of an inverse relationship between increasing adherence to the diet and incidence of new-onset depression. A conference on empathy took place at the end of September 2009 and the conference website can be found here. A study in the BMJ showed an increase in the number of prescriptions of antidepressants from 1993 to 2004 and this was attributed to the use of long term prescriptions. There is further coverage here.
In a cross-sectional study of symptoms in people with bipolar disorder (n=88) published in the journal of the World Psychiatric Association, the researchers found a significant association between the mixed affective state and negative cognition and hyperactivity (article freely available here). In a study of people in the Andean highlands in Ecuador (n=167), the researchers used the Spanish version of the Beck Depression Inventory II and identified that the scores on the somatic component of the scale were significantly higher than the cognitive component (article freely available here). The researchers interpreted this as resulting from the influence of culture on the expression of the depressive illness. There is an interesting article on the National Dementia Research Brain Bank here.
A small case-control study involving people with Bipolar Disorder, unaffected first-degree relatives and controls and using Diffuse Tensor Imaging found evidence of reduced structural integrity in the corpus callosum genu as well as the left superior and right inferior longitudinal fasciculus. There was also evidence of distributed areas of reduced structural integrity in unaffected relatives but it will be interesting to see the results of larger replication studies (Chaddock et al, 2009). In a study with 86 subjects, people with intermediate onset bipolar disorder were found to have increased a significant reduction in sulcal index in the right prefrontal cortex compared to controls and people with early onset bipolar disorder (Penttilä et al, 2009).
A prevention program in the Netherlands involving CBT Bibliotherapy, watchful waiting, CBT problem-solving treatment and referral for medication as necessary halved the incidence of depression and anxiety in a sample of 170 people over the age of 75 with subthreshold anxiety and depression (van’t Veer-Tazelaar et al, 2009). Using Magnetic Transfer Ratios (a measure of white matter integrity), 16 people with type II diabetes and depression were found to have significantly lower MTR’s bilaterally in the head of the caudate compared with 22 people with type II diabetes without depression and a control group with diabetes or depression (Kumar et al, 2009). A blunted prolactin and cortisol response to clomipramine infusion was found in people with remitted depression and a history of major affective disorders compared to a control group (Cordes et al, 2009). In an RCT with 60 people with unipolar depression being treated with Imipramine, zinc supplementation was found to increase the speed of onset of response and efficacy and it will be interesting to see the results of further replication studies (Siwek et al, 2009). In a deep brain stimulation study which involved 2 subjects, stimulation of the caudate nucleus was found to be effective for OCD symptoms and simulation of the nucleus accumbens was found to be effective for improving depressive symptoms and this larger studies are indicated (Aouizerate et al, 2009). A small study (n=14) found that Verenicline, a nicotinic acetylcholine receptor partial agonist was associated with a significant improvement in mood (using a self-report measure) and 44% achieving abstinence from smoking with the authors recommending further research to confirm these findings (Philip et al, 2009).
A brief discussion of an article reviewing neurobiological factors in depression. A longitudinal study identifies risk factors for development of depression in adolescence. Research looking at mortality in Bipolar Disorder. Cortical thinning in the right hemisphere was associated with depression in a study looking at 131 people with familial depression. Depression was a significant predictor of developing heart disease in a longitudinal study of Vietnam War veteran twins. An association between diabetes and post-partum depression was found in this study. Circumstantial evidence suggests that deficiencies in monoamine levels can be compensated for. The authors of a small study found that people with depression were less able to learn beneficial information in a special test of novel attitudes although it would be interesting to see further replication in larger samples. Prevalence of depression in epilepsy was found to be increased almost two-fold in the Canadian Community Health Survey.
A randomised control trial looked at computerised CBT (cCBT) delivery in a primary healthcare setting. The 303 participants with depression were allocated to treatment as usual, cCBT (using the Colour Your Life program and without support) or cCBT plus treatment as usual. In the first two groups there was a relatively poor adherence to treatment but in the analysis there was found to be no significant difference between the groups on the primary outcome measure – BDI-II scores. The authors conclude that supported cCBT might fare better. It would be interesting to see if the program could be modified to increase adherence rates (de Graaf et al, 2009). In a study of 1147 parents (>60 years old) whose children migrated out of the district of the parent there was found to be a decreased prevalence of depression in the parents (article freely available here)(Abas et al, 2009). In an open-label flexible-dosing trial of Ziprasidone for acute bipolar mania (n=65), 98% of the adverse events were classed as mild to moderate in severity. Improvement in Mania Rating Scale scores was comparable across the examined subpopulations – those with mania alone, mixed episode and also with or without psychosis (Keck et al, 2009).
In a relatively small study (n=51) people with and without depression were placed on a weight reduction program and an average 8% weight loss in the depression group was significantly association with an improvement in depression scores although it will be interesting to see the results in the final published form. There has been a relative large study comparing people with Tourette’s and OCD with healthy controls and finding no significant evidence of the former conditions with Streptococcal throat infection. There is contrary evidence which suggests that Strep throat infections can be associated with autoimmune processes which involve the central nervous system and these are termed PANDAS. An American study provided evidence of the cost-effectiveness of telephone-based Cognitive Behavioural Therapy for depression in primary care (covered here and here) although the application of these results will depend on local protocols and service structure. The study is in the Archives of General Psychiatry. Aaron Beck who developed CBT was awarded the Lasker prize for clinical research.
The British Journal of Psychiatry featured two interesting studies on antidepressants. The first featured a patient rating scale for antidepressant side-effects – the Antidepressant Side-Effect Checklist (AEC) which is included in the Appendix for the paper (Uher et al, 2009). The researchers compared this patient rating scale with a clinician rating-scale, the UKU in 811 subjects with depression who were participating in an open-label trial comparing Nortriptylline with Escitalopram. The Nortriptylline was included because of a strong affinity for noradrenergic receptors (it would have been interesting to see whether similar findings would have occurred with Reboxetine). They found that after correcting for the severity of depression, the AEC scores predicted discontinuation of escitalopram (although curiously not the Nortriptylline) and validated the use of the instrument for the purposes of establishing side-effects in antidepressants. In another study, this time qualitative, the researchers explored the emotional side-effects of the SSRI’s. The responses from the participants were grouped into 7 categories and there were many interesting comments from the participants (Price et al, 2009). Both a reduction in ‘positive’ and ‘negative’ emotions were reported and there was some supporting evidence from an analysis of comments on several depression related online forums. The authors suggest further quantitative studies to investigate the findings from this study.
A meta-analysis of prospective studies of people with cancer and comorbid depression found that depression was associated with a significant increase in mortality and the paper is freely available here at the time of writing as well as being reported on here.
Research in Psychosis
In a study in which two psychiatrists assessed 100 inpatients, the diagnosis of schizophrenia was found to occur more frequently when using ICD-10 criteria compared DSM-IV and the researchers suggest that this might be due to the absence of an exclusion of an affective syndrome in ICD-10 (although there are references to affective symptomatology in ICD-10)(Cheniaux et al, 2009). In a longitudinal structural MRI study, people with schizophrenia were divided into good and poor outcome groups and in the latter group there was found to be a significant assocation with reduction in the volume of the putamen (Mitelman et al, 2009). In an 18-week double-blind flexible dosing study (n=147) of Clozapine and Ziprasidone in people with treatment-resistant schizophrenia the researchers concluded that both medications showed similar efficacy with reduction in PANSS scores being the primary outcome measure (Sacchetti et al, 2009). There was a recent study in the New England Journal of Medicine, looking at both typical and atypical antipsychotics and finding an increased risk of cardiovascular events which was dose dependent. In an Eli-Lilly funded study of 7658 people with schizophrenia switched to or initiated on one of four antipsychotics, the median time to discontinuation was 30 months for Olanzapine, 23.1 months for Risperidone, 13.9 months for Quetiapine and 12.5 months for Haloperidol. There is a critical period hypothesis which states that there is a critical period of a psychotic illness during which time deterioration occurs more rapidly. In an 8 year prospective cohort study of people with first-episode psychosis the duration of untreated psychosis predicted outcome at the end of the study. However due to the study type there was no comparison group. The authors suggest that the prodromal period should be included within the critical period. An imaging study with 17 people at risk of psychosis, 10 with psychosis and 15 controls found that there were intermediate patterns of activation in the at-risk group between controls and those with psychosis. Specifically this involved the anterior cingulate cortex and inferior frontal cortex in a verbal fluency task and the dorsolateral prefrontal cortex, inferior frontal cortex and parietal cortex in the N-back task.
In a small study with 13 subjects with schizophrenia and formal thought disorder and 13 controls there was found to be a correlation between perfusion of left fronto/temporoparietal language areas and severity of formal thought disorder and between reduced temporoparietal grey matter volume and severity of formal thought disorder. In a longitudinal study there was found to be an association between length of untreated psychosis and functional outcome at 12 months with the authors suggesting that treatment options can be developed at earlier (i.e. prodromal) phases of the illness. A recent meta-analysis of blinded studies of head-to-head 2nd generation antipsychotics found that there were differences in efficacy. The authors utilised metaregression and sensitivity analyses to examine bias for factors such as industry sponsorship and concluded that the differences remained.In a Janssen-Cilag sponsored 3-year longitudinal study involving 211 people taking Risperidone Long-Acting injections looked at discontinuation. The discontinuation rate at 3 years was 84% and factors associated with discontinuation included age (younger) and duration of illness (longer). The authors conclude that outcome could be improved by targetting treatment and also comment on dosage (Taylor et al, 2009). There was some evidence of a benefit in early psychosis for augmentation with allopurinol and it would be interesting to see how this develops (Dickerson et al, 2009). A meta-analysis of studies looking at Theory of Mind in schizophrenia identified heterogeneity secondary to state and also differences in tasks but concluded that there was evidence of a trait from the persistence after remission (Bora et al, 2008). In another study, 10 hours of chess tuition and playing was found to improve performance on the Stroop and Tower of London tests in people with schizophrenia relative to a treatment as usual group. The authors suggest this represents an improvement in planning abilities due to playing chess which fits with other studies of chess players although it will be interesting to see the results of further research in this area (Demily et al, 2009). Another intriguing study looked at emotional intelligence in people with schizophrenia using a validated test – the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). The researchers found that in 50 people with schizophrenia and 39 non-psychiatric controls, the people with schizophrenia scored significantly worse on the total MSCEIT and that their scores also correlated with negative symptoms, disorganised symptoms and community functioning (Kee et al, 2009). A small RCT (n=39) in people with schizophrenia showed a significant and clinically relevant improvement in PANSS scores with the addition of Mirtazapine to a first-generation antipsychotic compared to FGA-plus placebo (Joffe et al, 2009). A meta-analysis found a trend towards higher schizotypal traits in people with non-right handedness compared to strong right handers (the non-right handed group consisted of left handers and mixed handedness) although there wasn’t a significant difference between strong right and left handers. The authors argue that these results support a model in which bilateral language organisation may relate to loosening of associations (Somers et al, 2009).
Lurasidone was found to significantly improve Brief Psychiatric Rating Scale scores in people with schizophrenia and an acute psychosis in this 6-week randomised double-blind placebo-controlled trial (n=90 in each arm of the trial) in Japan (Nakamura et al, 2009). In a small open-label trial of augmentation with Donepezil in 28 people with schizophrenia there were found to be significant improvements in attention, memory and other cognitive measures (Chung et al, 2009). A naturalistic study (n=325) provided evidence that had greater efficacy for treatment of schizophrenia (using outcome measures including the PANSS) than chlorpromazine or haloperidol (Ravanic et al, 2009).
In an interesting development, two authors have proposed a group of 22 ‘facts’ that can be used in constructing models of schizophrenia (MacDonald and Schulz, 2009). People with schizoaffective disorder and related affective disorders were significantly more likely to carry the val66Met polymorphism of BDNF than people with schizophrenia in this study of 381 people with schizophrenia, affective disorders or schizoaffective disorder and 222 controls (Lencz et al, 2009). A comparison of women with and without childhood abuse found that the former group were significantly more likely to develop psychosis in adulthood in this case-control study (cases n=181, controls n=246). The same finding was not identified in men. However further prospective cohort studies could explore causality (Fisher et al, 2009). Anandamide which binds to cannabinoid receptors was found to be elevated in 27 people with the prodromal state of psychosis compared to 81 controls and the authors suggest that Adandamide may be protective in the prodromal phase (Koethe et al, 2009). The authors of a paper propose that Toxoplasma Gondii may produce psychosis in hosts as a mechanism to enhance fitness of the pathogen and advocate further research to test their hypothesis (da Silva and Langoni, 2009). The authors of a genome wide analysis (analysing the data from a previously published study) found significant evidence of an association between the research diagnostic criteria Schizoaffective Disorder Bipolar type and variations in the GABA receptor particularly GABRB1 which they argue is further evidence in support of the diagnosis of Schizoaffective Disorder and it will be interesting to see further studies examining this potential relationship more closely (article freely available here)(Hamshere et al, 2009).
Age of onset of psychosis in families with more than one member with schizophrenia was found to have a significant heritable component in this study which included 717 families in Mexico and Central America (Hare et al, 2009). A Swedish study looking at 3 birth cohorts and a using semi-structured interview showed a 1% prevalence of psychosis in non-demented people aged 70, 78 and 82 (Sigstrom et al, 2009). In a study of 125 people with schizophrenia, physical activity levels were comparable to population norms although 70% were classed as being overweight and the authors suggest possible mechanisms to account for the difference in their sample (McLeod et al, 2009). In a study of 35 people with schizophrenia, 15 had passivity symptoms and 20 did not. Those with passivity symptoms were significantly more likely to underestimate time durations (Waters and Jablensky, 2009). A widely reported case-control study in Nature (also here, here, here and here although some of the reported sample sizes differ) looked at copy number variants in people with (n=3332) and without (n=3587) schizophrenia. The researchers found that there was a large number of variants that were associated with schizophrenia and were also found in people with bipolar disorder. Furthermore these variants were estimated to contribute to a third of the risk for schizophrenia. Two further studies were conducted by different groups and the results from all three were pooled. Significant associations were found with the Major Histocompatability Complex on Chromosome 6 as well as the myosin gene.
A relatively small prospective imaging study provided evidence of gray matter loss over a mean 1.8 year follow-up period in people with First Episode Psychosis (FEP) and those at ultra-high risk of developing psychosis (UHRNP). In both FEP and UHRP there was significant grey matter loss in the planum temporale and planum polare and in FEP there was also gray matter loss in the left Heschl gyrus which was significantly associated with delusional severity (Takahashi et al, 2009). Grey matter volume in the Insular Cortex was reduced in a sample of 31 people at Ultra-High Risk of progression to psychosis who later progressed (UHR-P) when compared with 66 people with Ultra-High Risk who did not progress (UHRPNP). Longitudinally there was found to be a significant reduction in grey matter volume in the insular cortex bilateraly in the UHRP group compared to both controls and the UHRPNP group (Takahashi et al, 2009).
A post-hoc analysis of 5 double-blind RCT’s comparing Olanzapine, Quetiapine, Ziprasidone, Aripiprazole and Risperidone concluded that Olanzapine did not differ from Aripiprazole but did show a lower loss of response than the other 3 antipsychotics at 24 and 28 weeks of treatment. Nevertheless it would be interesting to see the results for longer periods of treatment (Stauffer et al, 2009). A small pilot study showed some benefit for a weight-reduction program in people taking second-generation antipsychotics compared to a control group. Larger replication studies would be beneficial (Blouin et al, 2009). A population-based case-control study looked at side-effects of psychotropic medication in people over the age of 67 and found an association between SSRI’s, Olanzapine and Amitripytlline and increased risk of hypertensions at 6-months after the medication was prescribed as well as a significant association between Olanzapine and diabetes at 6-months while conventional antipsychotics were associated with a reduction in the incidence of hypertension (Kisely et al, 2009). A placebo-controlled trial of Mirtazapine as an adjunct to atypical antipsychotics for schizophrenia found no evidence of benefit in a small 6-week study with 40 participants – 20 in each arm (Berk et al, 2009). A change in prolactin levels was association with olanzapine treatment response in an open label study (Chen et al, 2009). People with non-affective psychosis and difficulties in social recovery were found to benefit from CBT when compared to treatment as usual although the authors recommend further larger replication studies (Fowler et al, 2009). Significantly greater weight gain for Risperidone and Olanzapine compared to placebo were identified from a database analysis of 21 placebo-controlled RCT’s (Parsons et al, 2009). A case of torsade de pointes occurring after haloperidol administration in a person with complete heart block was identified in this paper (Ginwalla et al, 2009). The authors of a review of 85 studies looking at coping mechanisms for psychosis conclude that multiple coping mechanisms most likely represent an optimal strategy (Phillips et al, 2009). A retrospective study of 52 elderly inpatients treated with Aripiprazole showed documentation of side effects in 17% of cases and that agitation was the most common side-effect occurring in 8% of people (Coley et al, 2009). Zolmitriptan was found to significantly improve neuroleptic-induced akathisia although not showing superiority to propranolol in this regards and the authors recommend a placebo-controlled trial (Avital et al, 2009). The authors of a systematic review of 33 structural MRI studies in people prescribed antipsychotics found evidence for an increased basal ganglia volume in people prescribed typical antipsychotics although other findings were less clear (Navari and Dazzan, 2009).
There is a discussion here of some of the recent genetic evidence of similarities between Schizophrenia and Autism in terms of analysis of copy number variants. The possible role of a form of interneuron known as the gliaform cell in psychosis is discussed in this article. A gene NOS1AP has been associated with schizophrenia in a study which used a new statistical method for establishing linkage. People with schizophrenia were found to be able to correctly discriminate hollow and normal faces in the ‘hollow-face paradigm in 94% of cases compared to 1% of controls. The authors identify this as evidence of a tendency towards ‘bottom-up processing’ in schizophrenia. An abnormal response to a glucose challenge was found in 16% of people with schizophrenia or related psychoses compared to none in the control group in a Spanish study.
An independent report by Professor Sube Banerjee, commissioned and funded by the Department of Health on the use of antipsychotics in dementia has been published (freely available here). Professor Banerjee has considered the evidence base including systematic reviews and meta-analyses regarding the use of antipsychotics in dementia and the report contains an estimate of the national morbidity and mortality associated with the use of antipsychotics in dementia. The report recognises the need for antipsychotics in certain situations and goes on to make a series of recommendations which focus in particular on clinical governance, recommendations which should lead to an improvement in the quality of care. The government have produced their response to this document (freely available here) and support these recommendations indicating that a national audit of antipsychotic use in dementia will be undertaken initially at six-months and then annually for at least three years and that the National Clinical Director for Dementia will take on a leadership role in this area. The Royal College of Psychiatrists has welcomed the report and responded here emphasising the need for input of specialist older adult mental health services. The response of the Alzheimer’s Society who have also welcomed the report is here. NHS choices have coverage of the report here.
A diffuse tensor MRI study looking at 76 people with schizophrenia and 76 controls found that in people with schizophrenia there were widespread regions of reduced fractional anisotropy (which is thought to be a marker for the integrity of white matter) in people with schizophrenia compared to the controls (Kanaan et al, 2009). A randomised-controlled trial of treatment as usual (n=40) versus individual and family CBT relapse prevention (n=41) in people with first episode psychosis found a significantly longer time to relapse in the relapse prevention group (Gleeson et al, 2009). In a study involving 173 people with schizophrenia-like psychosis, schizophrenia spectrum disorders and depression and 64 controls looking at a number of measures including emotion and self-esteem, the best fitting model for paranoid delusions including pessimistic thinking style and impaired cognition as explanatory factors (Bentall et al, 2009). In a sample of 451 85-year-olds in Sweden, paranoid symptoms were associated with agitation and irritability/anger in people with and without dementia and the authors emphasise the importance of treating these symptoms (Ostling et al, 2009). The neurobiology of affiliation is an area with a number of implications for psychiatric disorders and is covered in this paper (Bora et al, 2009). A causal model for drug-induced diabetes is proposed in this paper (Starenburg and Bogers, 2009). In a retrospective case-note review of 89 people started on Aripiprazole and 132 people started on Quetiapine over 5 years, improvement using Clinical Global Impression scores was broadly similar with 74% improving with Aripiprazole and 67% with Quetiapine (Shajahan et al, 2009). A retrospective cohort study of 6957 national service conscripts showed an association between lower performance on a national examination given at the end of 6 years of primary education and development of schizophrenia spectrum disorders (Chong et al, 2009).
There is evidence that copy number variants may play a role in the pathogenesis of schizophrenia. Post-partum psychosis is associated with age this reported study. An American study looked at antipsychotic prescribing and found that a majority of patients were receiving antipsychotic medication without a diagnosis of bipolar disorder or schizophrenia and that a number of the prescriptions were of brief duration and of a subtherapeutic dose. Initial results suggest that Modafanil may reduce Olanzapine associated weight gain. The DISC 1 gene which is associated with Schizophrenia has been found to influence neural development and other relevant genes in two recent studies. The Schizophrenia Research Forum have coverage of a recent murine study showing an association between mutations in the dysregulin gene (which has been associated with schizophrenia in genome wide association studies) and the function of fast-spiking interneurons.
Research in Dementia
The authors of an imaging study (n=comparing people with Alzheimer’s Disease or Mild Cognitive Impairment with healthy control used a ligand for the Alpha4Beta2 nicotinic acetylcholine receptor and found no significant difference between the groups after controlling for multiple confounders before concluding that this supported the hypothesis that aceytlcholine reductions are observed late in Alzheimer’s Disease (Mitsis et al, 2009). A double-blind placebo-controlled trial of Donepezil in Vascular dementia (n=707 completers) showed evidence of a small but significant improvement on ADAS-cog scores (0.6-1.15 points) at 54 weeks (Wilkinson et al, 2009). In a survey of hospice Medical Directors in the USA anticholinesterase inhibitors and NMDA receptor antagonists were prescribed in a small subset of people with advanced Alzheimer’s Disease and reasons given included stabilising cognition and addressing problematic behaviours suggesting a benefit for formal studies to address these issues (Shega et al, 2009). A small study (n=29) in female Chinese caregivers of people with dementia in Hong Kong found a significant improvement in self-efficacy of managing problematic behaviours in the people they were caring for (Au et al, 2009). In a retrospective analysis of data from an RCT of Rivastigmine in Mild Cognitive Impairment (n=1018) there was found to be a significant reduction in the rate of cognitive decline of male BuChE-K carriers (a variant of the Butylcholinesterase Enzyme Gene) and also in female BuChE wt/wt carriers (Ferris et al, 2009). The authors of a recent randomised double-blind study of Donepezil in young adults with Down Syndrome treated over a 12-week period concluded that the results supported the safety of Donepezil in people with Down syndrome although the efficacy results were more difficult to interpret (Kishani et al, 2009). In a post-mortem study there was found to be a case of Alzheimer’s Disease without uptake of radiolabelled Pittsburgh compound B (PIB) and the authors suggest that this compound might bind differentially to various forms of multimeric ABeta. The implication if this holds is that a PIB negative finding might not always exclude the diagnose of Alzheimer’s Disease. However as this is a single case, it will be interesting to see if these results are replicated (Rosen et al, 2009).
An intriguing study looked at the possibility that Rivastigmine could act partly through the induction of heat shock proteins for which there is evidence of a neuroprotective role (Zhou et al, 2009). The authors of a recent meta-analysis on MCI concluded that the risk of progression to dementia may be reduced by anticholinesterase inhibitors. This is a complex area and no doubt this debate will continue (Diniz et al, 2009). The authors of an interesting study looking at lacunar infarcts concluded that memory was more likely to be affected if the thalamus, putamen and pallidus were affected rather than the internal capsule and caudate nucleus (Benisty et al, 2009).
There has been widespread reporting in the UK media about a study investigating the use of antipsychotics in people with dementia which shows increased mortality relative to those taking placebo. The dementia antipsychotic withdrawal trial (DART-AD) was a 12-week placebo-controlled trial in which patients in nursing homes were continued on one of five antipsychotics (thioridazine (which has since been withdrawn from general use), chlorpromazine, haloperidol, trifluoperazine and risperidone) or switched to oral placebo. 165 people were included in the trial, evenly divided between the two groups and survival in the groups were found to be 70% v 77% at 12 months (antipsychotic v placebo), 46% v 71% at 24 months (antipsychotics v placebo) and 30% v 59% at 36 months (antipsychotics v placebo). Important question here however include the indication for the antipsychotic and the choice of antipsychotics for inclusion.
In a cross-sectional study of 76 people without dementia (mean age 67, 36 with mild cognitive impairment), FDDNP-PET signals (FDDNP stands for 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-napthyl}ethylidene) malonitrile and is a compound which binds to plaques/tangles) was correlated with older age, impaired cognition and APOE-4 carrier status. In a 6-year Swedish cohort study looking at risk of dementia and the traits of neuroticism and extraversion, there was found to be an increased risk of dementia in those with high neuroticism and high extraversion compared to those with low neuroticism and low extraversion (Hazards Ratio 0.51 (CI 95% 0.28-0.94). An autosomal dominant condition similar to leukodystrophy has been suggested to account for a presentation similar to Frontotemporal Dementia after a series of autopsies were undertaken in affected people. What is interesting about this condition is that it sometimes doesn’t present till the eighth decade of life. After cells have differentiated, recent research suggests that the nuclear pore complex deteriorates in an age-dependent manner allowing leakage of proteins into the surrounding cytoplasm (and also the reverse). This would suggest a need for new supplemental treatment approaches. A relatively large 12-month follow-up study of 325 people who had undergone 123I-FP-CIT-SPECT scans found that the SPECT scans were useful in discriminating Lewy Body from non-Lewy Body Dementia. A rating panel utilised other clinical measures of the presentation. These ratings were then compared with the SPECT scan results. In the probably Lewy Body Dementia group the sensitivity was 63% and the specificity was 100%. It would be interesting to see the results at two years. There is a description of a care pathway for advance decisions and power of attorney for use in people with Huntington’s Disease.
Alan Johnson, Health Secretary, unveiled a national dementia strategy to Parliament. There was a case-control study finding in 13693 twins (65 years or older), that the risk of dementia was associated with a 2-fold increase in (people with) diabetes. This is an interesting finding as there may be modifiable risk factors and also there is a relatively obscure hypothesis about potential CNS actions of insulin. However the obvious confounders in such an argument are the cardiovascular risk factors but this must at least begin a theoretical debate in this area. One of the difficulties that can occur in research in dementia is when the potential subject does not have the capacity to consent although there is appropriate guidance in this area. In a recent survey of 538 people over the age of 65, 92% of people were found to be willing to give blood and 75% to give blood and undergo lumbar punctures as part of a research study at a future point if they no longer had capacity, even if the research didn’t benefit them directly. An emerging theory with supporting data is that there are cortical hubs in the brain, areas which are well connected in which ABeta plaques are more likely to form (using PIB-PET). In a study of people with probable Alzheimer’s Disease, 140 were prescribed memantine and a cholinesterase inhibitor, 387 a cholinesterase inhibitor only and 416 were prescribed neither. Although there was no significant effect on time to death, ChEI’s significantly delayed time to nursing home admission compared to without ChEI’s and the addition of memantine significantly delayed admission compared to the ChEI alone group.
The consultation document is here. A slightly abstract piece of research is one at the cellular level, but i’ve included it here as it has important implications for memory. Thus in Nature Neuroscience, Cooper and colleagues have used a patch-clamp recording technique on layer V Pyramidal cells in the Prefrontal Cortex and found that the cell’s depolarisation on receiving input from another cell continues for up to a minute even when the other synapsing neuron is no longer firing. As cocaine has an influence on working memory and also eliminated the depolarisation, the authors conclude that this cell was retaining a memory. A study in healthy elderly (average age 60 years) volunteers showed an improvement in verbal memory with calorific restriction together with a reduction in C-Reactive Protein and Insulin levels. The results will need further replication but fit with a body of evidence emerging in the area of calorie-restriction. However, such approaches have potential to compromise the immune system and the Department of Health has given advice about not reducing calories during the winter months when infections are more prevalent. Larger and longer term studies will be required before any recommendations can be safely made.
A group from Oxford have presented the results of a novel approach to diagnosing Parkinson’s Disease. They hypothesise that the distribution of metal ions in neurons in Parkinson’s Disease is affected by the disease process and that it can be used in identifying the disease at an early stage. They argue that the method of preparing tissue before analysis has the potential to influence the iron content of cells and they have developed and are using a method that they state does not alter the iron composition of cells. They then used the UK National Synchrotron which can focus beams in a small area of the tissue to characterise the form in which the iron is stored very precisely using a technique referred to as Microfocus Spectroscopy. They are due to formally announce their findings at the AAAS in which they have identified an altered distribution of iron in cells in Parkinson’s Disease. The next stage is to use this information to interpret MRI studies. While this novel approach is encouraging it will be interesting to see the published research and to see the results of MRI interpretations.
In a study of family caregivers of people with Alzheimer’s Disease in Turkey, there was found to be a significant association between caregiver burnout and caregiver anxiety as well as patient’s self-maintenance (Yilmaz et al, 2009). The authors of a study looking at anosognosia found that this may impact on the results of self-rated quality of life measures in people with Alzheimer’s Disease (Berwig et al, 2009).
Performance on memory tasks was inversely correlated with the number of neurofibrillary tangles in the hippocampus on post-mortem. There was also an inverse correlation between memory performance and NFT’s in the entorhinal cortex, CA1 and subiculum (Reitz et al, 2009). CSF ABeta42 levels were inversely correlated with brain atrophy in Alzheimer’s Disease and the authors suggest that this may result from increased ABeta42 aggregation in the disease process (Fagan et al, 2009). A longitudinal study which involved autopsy found an inverse correlation between carrying the APOE2 gene and cognition in those over the age of 90 but a significant correlation with Alzheimer’s Disease neuropathology (Berlau et al, 2009). Risk factors that Alzheimer’s Disease and Diabetes share in common are examined in this review article (Gotz et al, 2009). A region on chromosome 8 was found to be significantly associated with Late-Onset Alzheimer’s Disease in a study involving 837 people with late-onset Alzheimer’s Disease (AD) and 550 controls (Nalls et al, 2009). Homocysteine levels were increased and paraoxonase levels decreased in people with Alzheimer’s Disease (AD n=51, VaD n=28, Mixed Dementia n=41) which was interpreted as a relationship between oxidative stress and the neurodegenerative process in Alzheimer’s Disease (Wehr et al, 2009). Anosognosia for amnesia (using the everyday memory checklist) was found to be positively correlated with disease progression in Alzheimer’s Disease in a longitudinal study involving 58 people with mild Alzheimer’s Disease (Akai et al, 2009). Acetylcholinesterase inhibitors were found to be have different effects on blood pressure and cerebral perfusion in Alzheimer’s Disease in this review (Claassen et al, 2009). An intriguing hypothesis that has been developed states that cognitive changes in Alzheimer’s Disease and normal aging may represent an ‘adaptive metabolism reduction program’ and it will be interesting to see the results of future studies testing this hypothesis (Reser, 2009). Another study shows evidence that cardiovascular risk factors do not influence progression of Alzheimer’s Disease (as opposed to onset) and it will be interesting to see the results of future replication studies (Abellan et al, 2009). As cognition became increasingly impaired using study data from two trials, there was found to be worse agreement between three measures of cognition – Alzheimer’s Disease Assessment Scale – Cognitive, Clinical Dementia Rating and MMSE (Tractenberg et al, 2009). An in vitro study provided evidence for neuroprotective effects of acetaminophen (Tripathy and Grammas, 2009). In a secondary analysis in the Video-imaging Synthesis of Treating Alzheimer’s Disease (VISTA) study, 74% of community-resident people with mild-to-moderate AD were found to misplace items recurrently and for 81% of these cases, this represented the inability to recall where items had been placed (Hamilton et al, 2009). A causal relationship to explain the association between Alzheimer’s Disease and glaucoma has been proposed as reduced cerebrospinal fluid pressure by a Belgian group (Wostyn et al, 2009). Placing of the minute hand on the clock drawing test was effective in discriminating people with Alzheimer’s Disease from controls (Leyhe et al, 2009). Iron levels were elevated in the hippocampus in 26 people with Alzheimer’s Disease compared to controls in a phase-imaging study of 26 people with Alzheimer’s Disease and 24 controls with potential diagnostic implications (Ding et al, 2009).
In a prospective study of community-based people with dementia (n=48) including post-mortem, visual hallucinations were associated with a higher frequency of neocortical lewy-related pathology, abnormal posture and gait than those without visual hallucinations. However in 59% of cases the diagnosis was Alzheimer’s Disease with concurrent Lewy Body related pathology (Tsuang et al, 2009). People with Lewy Body Dementia (n=29) were significantly more likely than those with Alzheimer’s Disease (n=33) to report difficulties with swallowing (Shinagawa et al, 2009). A component of inclusion bodies – trans-activation-responsive DNA-binding protein 43 (TDP-43) has been found in familial British Dementia by a Canadian group (Schwab et al, 2009). In a 5-year prospective cohort study, over 70% of people with mild behavioural impairment converted to dementia and were more likely to develop Frontotemporal Dementia than Alzheimer’s Disease and the authors suggest that MBI may be an FTD prodrome (Taragano et al, 2009). In a small case control series of Frontotemporal Dementia, 12 people with MAPT gene mutations were found to have greater grey matter loss in the frontal, parietal and anteromedial temporal lobes copared to the control group while the 12 people with PGRN gene mutations were found to have greater grey matter loss in the frontal, parietal and posterior temporal lobes than controls (Whitwell et al, 2009).
People with Mild Cognitive Impairment and Alzheimer’s Disease were found to perform worse on time estimate tasks than a younger comparison group and this effect was independent of episodic memory (Rueda and Schmitter-Edgecombe, 2009). An MRI study showed more temporal grey matter loss in people with Prodromal Alzheimer’s Disease compared to amnestic mild cognitive impairment (Rami et al, 2009). A study freely available here showed a significant relationship between MRI measured hippocampal loss and CSF AB1-42 in mild cognitive impairment and ApoeE allele in Alzheimer’s Disease (Schuff et al, 2009). A small study (n=20) found evidence of altered connectivity between the dominant hand area in the motor cortex and language related areas using a combination of motor evoked potentials and transcranial magnetic stimulation in people with amnestic mild cognitive impairment (Bracco et al, 2009). In a study looking at 10 people with amnestic MCI and people with AD (11 mild; 17 mod; 15 severe) there was found to be a significant correlation between the size of the white matter lesions in the periventricular and subcortical areas and severity of dementia (Targosz-Gajniak et al, 2009). A Dutch Randomised Controlled Trial found that a multidisciplinary diagnostic approach was cost-effective for evaluation of cognitively impaired elderly (Wolfs et al, 2009). Using data from 383 MR volumes in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and MR based shape analysis, subjects with MCI and Alzheimer’s Disease were found to have an outward-deformation in the lateral ventricles. There was also evidence of inward deformation in the anterior-lateral and ventro-lateral thalamus (Qiu et al, 2009). The Memory Impairment Screen Plus (MISplus) was found to be more effective at predicting conversion of MCI to AD than a number of other measures including the MMSE when a threshold score of 2/6 was used in this longitudinal study (Dierckx et al, 2009). Reduced whole-brain cortical thickness and DTI measurements in the left temporal region were effective in differentiating people with MCI and controls particularly in combination (Wang et al, 2009). The clinical dementia rating scale and neuropsychological criteria were discordant for diagnosis of MCI in 37% of cases in a study of 3063 elderly people with dementia living in the community (Saxton et al, 2009). In a cross-sectional study looking at 109 people aged 65 years or older with depression (who had responded to treatment) and 65 controls who had never experienced depression, the depressed group had just under twice the prevalence (38% – 2/3 amnestic, 1/3 non-amnestic) of Mild Cognitive Impairment as the control group (Bhalla et al, 2009). In a meta-analysis of 14 studies which looked at hippocampal volume in people with Mild Cognitive Impairment and Alzheimer’s Disease compared to controls there was found to be greater atrophy in the left hippocampus in both MCI and AD groups as well as a greater degree of atrophy in AD subjects (24.2% left, 23.1% right reduction in hippocampal volume) than in MCI (12.9% left, 11.1% right reduction in hippocampal volume) with both being significantly greater than controls (Shi et al, 2009).
A study (article freely available here) suggests a role for the phosphatidylinositol 3-kinase in the suggested neuroprotective role of the anticholinesterase inhibitors . In another study there was evidence suggesting that Galantamine acted via a calcium/calmodulin-dependent protein kinase II and protein kinase C activation in effecting a suggested improvement in Long Term Potentiation (Moriguchi et al, 2009). A phase I study (n=6) showed preliminary evidence that combining an error free learning approach with Donepezil in people with Alzheimer’s Disease improved performance on a naming task (Rothi et al, 2009). A recent study looked at a 1 year follow-up of Donepezil in 189 people with severe Alzheimer’s Disease and the authors concluded that Donepezil was safe and effective during this period (Homma et al, 2009).
In a GSK funded population-based longitudinal study involving 2050 people without dementia and 587 people with dementia, psychological and behavioural symptoms were found in most people with dementia. There was a finding that depression and anxiety prevalence decreased at later stages of the illness although they were elevated in the initial stages (Savva et al, 2009). A compound polybutylcyanoacrylate has been demonstrated to be effective at delivering proteins into neurons in vitro (Hasadri et al, 2009). Neurosonology has been proposed as a useful measure for investigating dementia (Demarin et al, 2009).The relationship between the blood-brain barrier and cognitive decline has been examined in a review paper in which a causal link is proposed (Popescu et al, 2009). In a systematic review of the use of long-chain omega-3 fatty acids there was found to be no reduction in progression of dementia although other studies have shown a reduction in cognitive decline in elderly people without dementia (Fotuhi et al, 2009). The authors of a Cochrane review found inconsistent evidence for clinical effects of Gingko Biloba in cognitive impairment and dementia (Birks et al, 2009). Although performance on tests wasn’t impaired by drinking caffeine containing drinks (ccd’s) there was found to be a linearly decreasing performance with an increase in age in those consuming ccd’s before the test and the authors caution that ccd’s should be considered when interpreting test scores (Lesk et al, 2009). A combination of folate and B12 deficiency was found to increase apoptosis and intracellular homocysteine to a greater extent than either alone in this in vitro study (Kifle et al, 2009). In the Lothian Birth Cohort 1936 study, APOE4 carrier study was found to interact with childhood intelligence in influencing old age non-verbal cognition (Luciano et al, 2009). In a study of 629 elderly people without dementia, vibratory threshold measured at the ankles/toes were significantly correlated with composite mobility scores (Buchman et al, 2009).
A recent study in Brain provided evidence for discriminating primary progressive aphasia (semantic type) from semantic dementia including changes in the middle and superior temporal gyri and inferior and medial temporal lobes (Mesulam et al, 2009). Putamen volume was found to be decreased in people with Frontotemporal dementia compared to people with Alzheimer’s Disease in one small structural MRI study (Looi et al, 2009). A retrospective post-mortem study provided further evidence of an overlap between Alzheimer’s Disease, Frontotemporal Dementia and Lewy Body Dementia using current diagnostic criteria (Piguet et al, 2009). A recent secondary analysis provided evidence that the Clinical Dementia Rating scale has remained valid for over three decades by correlating the scores with those of other psychometric measures (Williams et al, 2009). In a location-matching task – a visual task there was found to be less activation on fMRI in people treated with Galantamine for 3 months in this small study (Bokde et al, 2009). A swedish follow-up study of up to 40 years showed a significant increase in risk of all-type dementia in people with mid-life obesity (odds ratio 1.59 p=0.002) as well as an increased risk of Alzheimer’s Disease and Vascular Dementia (Hassing et al, 2009).
In a study of relevance to old age liaison services, the authors of a longitudinal study looking at older adults admitted as emergencies to hospital characterised the prevalence of dementia according to age stratifications. The authors found an as expected increase in prevalence with age rising to 75% over the age of 90 in women and 48.8% in men over the age of 90. 41.3% of admissions resulted from urinary tract infections or pneumonia(Sampson et al, 2009). In a case-control study of people with Late-Onset Alzheimer’s Disease (AD) (217 people with AD and 76 controls) there was found to be a significantly increased proportion of people with type A personality types compared to controls (Nicholas et al, 2009). In a small study comparing 13 people with frontotemporal dementia with 12 people with Alzheimer’s Disease and 20 people with Semantic Dementia using structural MRI longitudinally (1 year) – there was found to be a significantly greater rate of atrophy in the frontal lobes in FTD than the other two groups and a similar rate of atrophy in the temporal lobe in semantic dementia and AD (Krueger et al, 2009). The researchers found that gamma-secretase, an enzyme implicated in Alzheimer’s Disease pathology binds to a class of transmembrane proteins known as tetraspanins (Wakabayashi et al, 2009) as well as to a number of other proteins. The tetraspanins have a number of different functions within the cell and it will be interesting to see how gamma secretase relates to these functions. There is further coverage here. Experimental evidence has shown that expression of IL-6 in murine brain can lead to removal of amyloid plaque by microglial cells. There has been significant evidence to suggest a role for inflammation in the disease process and these new findings show that the relationship between inflammation and build up of Amyloid Plaques in the brain is complex. In one study there was found to be an association between plasma levels of ABeta42 and risk of conversion from Mild Cognitive Impairment to Alzheimer’s Disease and it will be useful to see further replication of these findings. Levels of a class of transcription factors NFAT’s (Nuclear Factors of Associated T-Cells) was significantly elevated in the hippocampi of subjects with Mild Cognitive Impairment or Alzheimer’s Disease compared to controls and at least one pathway has been suggested between activation by Amyloid plaques and expression of regulated genes.
There have been a lot of studies looking at the possible benefits of the ACE inhibitors in reducing the risk of dementia but a new study gives a twist to the story. This is a prospective study involving people without dementia at baseline and the researchers selected 1074 participants from the cohort. They found that taking a centrally-acting ACE-inhibitor was associated with a 65% decrease in cognitive decline (using a modified version of the Mini-Mental State Examination) and that taking a peripherally-acting ACE-inhibitor was associated with a 73% increased risk of dementia compared to those taking other antihypertensive medication. This study occurs in the context of other studies suggesting a benefit of the ACE-inhibitors in dementia on various outcome measures. However it is important to note that the participants in this study were being treated with antihypertensives and were thus a selective group. This may be an important finding and the investigation of the actions of the centrally-acting ACE-inhibitors may well give some important insights into dementia. It will be very interesting to follow the necessary subsequent research in this area. The authors of a longitudinal Finnish study involving 2000 middle-aged subjects who were followed up over 20 years later provided further evidence that the APOE 4 variant was associated with a higher prevalence of Alzheimer’s Disease. A similar increase was also found in association with being separated from a partner before age fifty. A study has provided indirect evidence that Granulocyte Colony Stimulating Factor (GCSF) might prevent the build up of Beta-Amyloid plaques in the brain which would be relevant in Alzheimer’s Disease. It will be interesting to follow further studies in this area.
Researchers at the University of California have identified an association between PTSD and increased risk of subsequent dementia using information from a database on 181,093 veterans over the age of 55-years although this association did not occur after controlling for depression, substance misuse and traumatic brain injury. An engineered protein that can be extracted from goat’s milk has and which interacts with the Beta-Amyloid protein has been suggested as a potential prophylactic agent for people who carry a variant of the Butylcholinesterase inhibitor gene. Several studies were presented at the 2009 International Conference on Alzheimer’s Disease which this year was in Vienna. Thus evidence was presented that strictly adhering to a diet for hypertension – the Dietary Approaches to Stop Hypertension (DASH) Diet was associated with improved cognitive functioning compared to those who didn’t adhere as consistently. There were 3,831 participants over the age of 65 who were followed up over 11 years. Adherence to the diet was represented by an ‘adherence score’ and associations with cognition were also found for fruit and vegetables as well as low fat dairy products. In another of the studies, a prospective study of 3075 people aged 70-79 there was a significant association between sedentary lifestyle and lower cognitive scores (modified MMSE) as well as between declining scores and declining physical activity. Another of the studies, this time in post-menopausal women showed a benefit on cognition for moderate exercise but a detrimental effect for chronic strenuous exercise although the study included a small number of participants (90) and it would be interesting to see further replication studies.
In one study, antibodies against ABeta peptide were found to decrease with advancing age and in people with Alzheimer’s Disease. Interestingly health control subjects were found to have antibodies against a number of antigens from plaques found in rare forms of dementia although the significance of this is far from clear. In another study, severe Chronic Obstructive Airways Disease was associated with significantly decreased performance on a validated 35-point cognitive scale compared to performance in a control group without COPD after controlling for possible confounders. The authors of a meta-analysis looking at 118 neuropsychological tests in the discrimination of Vascular Dementia and Alzeheimer’s Disease concluded that only 2 tests were effective in discrimination – the emotional recognition and delay recall tasks – but concluded that multiple sources of information were needed for the purposes of discrimination. In a similar vein, a team at the Mayo Clinic have been developing an MRI protocol for discriminating Alzheimer’s Disease, Frontotemporal Lobar Degeneration and Lewy Body Dementia. The protocol is referred to as the STAND-Map protocol (Structural Abnormality Index). The protocol is apparently effective at discriminating ‘75-80%’ of cases although the results are due to be presented at a conference and it will be interesting to have a closer look at the breakdown of figures. Mutations in the protein LRKK2 are associated with Parkinson’s Disease and the authors a new study found that another protein referred to as CHIP binds to LRKK2 and modifies the levels of LRKK2 and it will be interesting to see the results of further studies in this area. A widely reported study showed an improvement in aged mice’s memory and attention when given large amounts of caffeine and an associated reduction in levels of Beta-Amyloid. Asystematic review of first and second generation antipsychotics found no evidence of efficacy in prevention of delirium in hospitalised patients and equivalent efficacy in treatment of delirium. In an interesting prospective study in older adults (n=49), MRI white matter hyperintensities were associated with a significant risk of developing dementia and the researchers correlated the volume of these lesions with the risk of developing dementia. A number of findings in Alzheimer’s Disease Research were reported at the British Pharmacological Society’s Summer Meeting in Edinburgh including evidence of a protective effect of flavinoids against the neurotoxic effects of Beta-Amyloid plaques. The REVEAL study provides evidence that disclosing information about APOE4 carrier-status to children of parents with Alzheimer’s Disease does not result in significant short-term psychological distress. A receptor has been found in the basal forebrain which responds to ABeta Protein in Amyloid plaques and may be related to the effects of plaques on acetylcholine levels.
Soy isoflavones supplementation was associated with a significant improvement in spatial memory scores in a 12-week double-blind placebo-controlled cross-over trial involving 34 men and the authors suggest that this may be related to ‘oestrogen activation’ (Thorp et al, 2009). In a 10-year follow-up of people without dementia (the Baltimore Longitudinal Study of Aging), in the mild cognitive impairment group compared to the control group (1017 observations) there was found to be a significant differences in volume change in a number of areas including the hippocampus, superior parietal and frontal regions (Driscoll et al, 2009). Homocysteine levels at baseline were significantly associated with rate of decline of CAMCOG scores in a study involving 94 people with Alzheimer’s Disease over the age of 75. There were at least 3 6-monthly visits but participants could be included for up to 9.5 years and the authors suggest an intervention trial (Oulhaj et al, 2009). The authors of a small case (n=14) series of people with subcortical vascular dementia or Alzheimer’s Disease were able to identify cerebral microinfarcts more commonly in the latter group particularly in the occipital cortex. They hypothesise that the Amyloid plaques may predispose to cerebral microinfarcts (Okamoto et al, 2009).
A tool that takes roughly 5 minutes to complete has been validated in a study which was published in the BMJ and detected 93% of people with Alzheimer’s Disease. Further studies will be needed but this has potential as a clinically useful tool (This paper has been reported widely in the media e.g. here, here, here, here and here). Researchers in Japan have identified a new CSF peptide (APL1beta28) that is associated with brain levels of ABeta42. Another study looked at risk factors that discriminated those who developed cognitive impairment from those who did not and found evidence that protective factors included exercise, not smoking, education and living with a partner. Mild cognitive impairment was associated with a 50% increase in mortality compared to controls and Alzheimer’s Disease was associated with a 300% increase in mortality compared to controls in this longitudinal study with 10-year follow-up. Intermittent exotropia in boys was associated with a higher use of psychiatric services in one study and it will be interesting to see follow-up studies in this area to validate and further clarify the association. Preliminary evidence suggests a reciprocal relationship between APP and a protein called Reelin where higher levels of Amyloid Precursor Protein are associated with lower levels of Reelin.
There is a recent study which provides evidence of a relatively small difference in the rate of decline of memory in those with Alzheimer’s Disease with or without diabetes. Those with diabetes had a slower rate of decline (although the effect size was relatively small) and it will be interesting to see further replication studies in this area. The authors of a paper using data from the prospective DESCRIPA case-control study found evidence that the characteristic CSF biomarkers of Alzheimer’s Disease increased risk of progression up to 27-fold relative to controls. More details can be found here. Preliminary evidence from one study found that Donepezil was associated with a reduction in progression to Alzheimer’s Disease in people with MCI and depression compared to the control group. The control group took either placebo and Vitamin E and the same effect was not found in people with MCI without depression. Images have been captured of neuronal synapses forming with the involvement of a protein – Neuroligin. A recent potentially important finding is that the response of glial cells is reduced in Alzheimer’s Disease and if this is so it could play a role in the degenerative process. This study did however have a small sample size and the findings are in opposition to the main theory proposing an immune response triggered by the Beta Amyloid plaque. It will be interesting to see the results of larger replication studies. A new protein found in the brain – hypoxia upregulated mitochondrial movement regulator (HUMMR) has been associated with the movement of the mitochondria within cells under conditions of hypoxia. The positioning is suggested to play a role in the removal of calcium ions from the intracellular environment under such conditions and there may be a role in hypoxia secondary to stroke (although further research is needed). Diffraction enhanced imaging has been used to image finer anatomical detail in brains in vivo although the synchotron produced radiation is not viable for clinical use, the researchers state that it establishes the principle of using imaging to obtain highly detailed in vivo images of Alzheimer’s Disease related plaques.
A potentially important study for understanding Huntington’s Disease has been published. The study suggests that a protein ‘Rhes’ which is found only in the corpus striatum interacts with the mutant Huntingtin protein and reduces protein aggregates which subsequent leads to neurotoxicity. There may be an increased research interest in Rhes after these results. Further evidence has been found for the efficacy of Rapamycin in epilepsy and that this can reduce the changes (mossy fibre sprouting) that occur after a kainate challenge with increasing evidence that this is through an action on a regulatory protein. In one post-mortem study all subjects with Lewy Bodies were retrospectively found to be functionally impaired although the calculation of an odds ratio was not possible (paper freely available here) (Byford et al, 2009). A type of swelling in the Purkinje cell axons referred to as a Torpedo was found to be elevated in people with Alzheimer’s Disease, Parkinson’s Disease and to a greater extent in cerebellar essential tremor in this post-mortem study (Louis et al, 2009). In an autopsy series (n=466) there was found to be no association between a measure of atherosclerosis in the circle of Willis (a marker of large vessel disease) and amyloid plaque in the frontal cortex or neurofibrillary tangles in the hippocampus (Luoto et al, 2009).
There is coverage here of a 20-year longitudinal study published in Neurology which identified associations with the development of mild cognitive impairment and it will be interesting to see how these findings inform further research in this area. This article looks at another study published in Neurology this time on Frontotemporal Dementia (FTD) and finding that 42% of subjects had a family history on the basis of a related outcome measure (see here for further information). There is coverage of the recent Society of Neuroscience conference in Chicago over at the Alzforum and this featured a number of presentations on Alzheimer’s Disease.
In a press release from the company that undertook the researhc, in conjunction with university researchers, the gene product for the gene Rps23r1 was associated with a reduction in two Alzheimer’s Disease related proteins amyloid beta and tau in a murine model. Developments in smart homes for people with dementia by a team at the University of Bath is covered here. Discussion of Fasudil which could be trialled in dementia here. A study suggesting 2 genes – CaIDAG-GEFI and CaIDAG-GEFII that are implicated in side effects from L-DOPA therapy in Parkinson’s Disease. A four-fold increase in cognitive impairment in cardiac failure discussed here. Evidence for the influence of cognitive training on D1 receptors. Discussion of a review of combining different drug classes in dementia and the research that is needed in this area. A meta-analysis looking at trials examining the effects of cognitive training in healthy elderly and progression of dementia and finding no benefit although more research is needed in this area. The results of a study looking at an off-road driving test that is used to make predictions of driving safety in Alzheimer’s Disease. Another study shows benefits on attention and memory for a cognitive training program. Another study providing evidence that cortical atrophy using MRI can be used to assess risk of conversion from MCI to Alzheimer’s Disease. Results from the ACCORD study providing evidence of an association between glycosylated haemoglobin levels and performance on four cognitive tasks. A randomised-controlled trial of software for improving speed on certain cognitive tasks showed evidence of an improvement on memory tasks. A study looking at retrospective recall of exercise patterns showed a positive association between increased exercise and decreasing risk of developing memory loss. The potential benefits of BDNF in dementia although clinical trial results are pending. Evidence that stimulating the immunce system with CpG ODN’s may be a useful mechanism for exploring amyloid plaque reduction in research in Alzheimer’s Disease. Evidence that ABeta4 clearance in the brain may be influenced by blood levels of ABeta4. A new model of Alzheimer’s Disease has been proposed in which netrin-1 is involved in creating synaptic connections and the amyloid plaque in breaking synaptic connections. A longitudinal study showing an association between longer working hours and performance on cognitive tasks.Further supporting evidence for the protective role of alpha secretase against Alzheimer’s Disease. Using Nuclear Magnetic Resonance imaging, a team has been able to identify the structure of a residue on the Tau Protein. A number of studies are reported on here which show a relationship between cognitive decline and metabolic risk factors including obesity, metabolic syndrome, and being underweight.
The GPR3 protein as a potential therapeutic target in Alzheimer’s Disease. A class of drugs – the secretase inhibitors – that are being trialled for Alzheimer’s Disease have been found to reduce traumatic brain injury related damage. A study in the new field of optogenetics suggests that deep brain stimulation in Parkinson’s Disease may be more effective when applied to the axons rather than the cell bodies of neurons in the subthalamic nucleus. Using a paradigm which involves fluorescence – FRET, a research team has found that alpha-synuclein which is implicated in Parkinson’s Disease is able to rapidly change shape. Alpha-synuclein is a member of a class of proteins – the ‘intrinsically disordered proteins’ which remain functional even when unfolded and which challenge the notion of a fixed 3-d protein structures always correlating with function. An exciting research project is 95% complete – the Alzheimer’s Disease Neuroimaging Initiative involves longitudinal MRI and PET scans as well as a number of other biological markers and the data is being made publicly available. A small study provides further evidence that hippocampal volume and rate of atrophy are associated with development of Alzheimer’s Disease. Diabetes and elevated LDL cholesterol levels have been associated with higher rates of progression in Alzheimer’s Disease in a longitudinal study involving 156 people with Alzheimer’s Disease. It will be interesting to see the results of larger replication studies. Inhibition of CK2 (a transport regulating enzyme) was found to interfere with the effect of Amyloid protein on tau transport in neurons. In a widely discussed study a peak age of 22 was found for cognitive abilities such as abstract reasoning and processing speed. fMRI studies supporting the sensory recruitment hypothesis which states that memories of a percept are stored in the area in which the perception occurs. One group report 80% accuracy in predicting which visual patterns a person is retaining in memory based on the fMRI data. A study which suggests that the formation of memories involving NMDA receptors occurs selectively during sleep.Preliminary evidence suggests that a constituent of Soybeans can degrade amyloid fibrils. Recent research suggests that a protein – Modifier for Cell Adhesion (MOCA) may play a role in a number of neurodegenerative conditions. A possible role for PARK9 in manganese processing. Sodium phenylbutyrate is suggested as a new therapeutic approach to be examined in Alzheimer’s Disease. A computational model – ResponseNet has been used to investigate the actions of proteins in Parkinson’s Disease. A one-leg balance test that is easy to administer was found to be associated with rate of cognitive decline in Alzheimer’s Disease in this study. A widely reported fMRI study by Demis Hassabis and Eleanor Maguire found a significant relationship between hippocampal activity and location in a virtual spatial environment.A study is showing a 74% increase in case of diabetes in the UK between 1997 and 2003 which is of significance in terms of another recent study looking at the relationship between dementia and diabetes.
The authors of a Cochrane review concluded that Rivastigmine was effective in the treatment of mild to moderate Alzheimer’s Disease after reviewing the results of 9 trials with a combined total of 4775 participants (Birks et al, 2009). A cotton seed extract with potential antidepressant effects was found to have hippocampal neurogenesis effects (Zhang et al, 2009). A recent study showed evidence of a neuroprotective role of Methylene blue in a model of optic neuropathy further supporting evidence from last year again as a neuroprotective agent in neurodegenerative processes (Rojas et al, 2009). Ibuprofen was associated with a reduction in the increasing rate of delta rhythms with time in people with mild Alzheimer’s Disease in this small placebo controlled study and the authors recommend further studies (Babiloni et al, 2009). A study looked at factors influencing length of time till admission to a nursing home for people with dementia and found that the characteristics of the care providers were important associations with time till admission (Habermann et al. 2009).
A virtual reality spatial navigation task was found to effectively discriminate between young healthy adults and older adults with Alzheimer’s Disease suggesting the theoretical utility of this paradigm although use within clinical practice will need to be further assessed (Zakzanis et al, 2009). Distinguishing between frontal function (using a frontal assessment battery) and posterior function (using a perceptual assessment battery) was effective in distinguishing between early-onset dementias and late-onset dementias in this small pilot study which looked at 23 people with dementia and 20 controls (Mendez et al, 2009).
99 people with early-onset AD were compared with 192 people with late-onset AD and the younger-onset group were found to have a more rapid decline particularly if they were APOE4 negative (van der Vlies et al, 2009). Tau deposition in an ageing sample (from the Medical Research Council Cognitive Function and Ageing Study) was found to proceed along a pathway which included the Entorhinal cortex, CA1 and dentate (Lace et al, 2009). People with early-onset Alzheimer’s Disease and AD associated with higher education were found to have thinner cortical thickness in a number of areas compared to a control group without cognitive impairment (Seo et al, 2009). A longitudinal study with post-mortem showed an association between Alzheimer’s Disease and evidence of vascular remodelling – alphavbeta3 immunoreactivity. This was also correlated with ABeta located in the hippocampus (Desai et al, 2009). The researchers in an in-vitro study that examined cholesterol levels in the cell membranes found significantly higher cholesterol levels in older neurons compared to younger neurons and also provided evidence that lower cholesterol was associated with less vulnerability to Abeta me There was found to be no significant difference between people with Alzheimer’s Disease and controls in brain-derived neurotrophic factor levels in a study with 196 people with equal numbers of controls and people with Alzheimer’s Disease (O’Bryant et al, 2009). Another study found an association between HDL and ABeta and the authors recommend a longitudinal replication study (Bates et al, 2009). diated toxicity (Nicholson and Ferreira, 2009). Diabetes was associated with a slower progression of Alzheimer’s Disease in this prospective Italian study of 154 people with mild-to-moderate AD and it will be interesting to see further replication (Musicco et al, 2009).
Epsilon4-positive APOE4 genotype was associated with significantly increased PIB uptake in the frontal, temporal and parietal cortex compared to the Epsilon4 negative genotype although no difference was identified in grey matter volume (Drzezga et al, 2009). The APOE epsilon4 alelle was associated with frontal and temporal lobe atrophy in this small study of 15 people with Alzheimer’s Disease (AD) who were carriers and 14 non-carriers with AD (Pievani et al, 2009). In a prospective study of 34 people with traumatic brain injury, outcome on the Glasgow Coma Scale at 6 months was significantly associated with serum tau protein levels on admission although further replication studies are needed (Liliang et al, 2009). Significant variability in immunosorbent assays for Tau and Abeta in CSF exist across the world and the authors of this study have called for a standardisation of procedures (Verwey et al, 2009). An in-vitro study provided evidence that alpha-synuclein’s N and C terminal domains were required for macrophage activation (Lee et al, 2009).
An association between amnestic mild cognitive impairment and cholinergic basal forebrain volume was found in this MRI study (Muth et al, 2009). A 3-year follow-up study provided evidence that reversion to no cognitive impairment was more likely to occur if mild cognitive impairment had been assessed on a single occasion compared to cases where it had been identified on repeated testing (Loewenstein et al, 2009). A combination of a logical memory test and the California Verbal Learning Test-II were found to be accurate in 87.5% of cases in discriminating cases of Mild Cognitive Impairment that converted to AD in this 4-year prospective study of 38 people with MCI (Rabin et al, 2009). People with AD or MCI were found to be impaired on a semantic fluency task relative to depressed and non-depressed controls (Lonie et al, 2009). Using data from subjects in a Mayo Clinic longitudinal registry and the Alzheimer’s Disease Neuroimaging Initiative (21 healthy controls, 32 people with amnestic MCI and 8 people with AD) amyloid deposition in AD (using PIB-uptake PET images) was found to proceed constantly but was not associated with clinical symptoms. However MRI determined brain atrophy (baseline image versus follow-up image comparison) was associated with clinical symptoms and the authors suggest that both imaging approaches are complementary (Jack et al, 2009).
A retrospective case series of 17 people who developed Frontotemporal Dementia identified prior diagnoses of bipolar disease and schizophrenia in 5 of the people. A supplementation of the case series with a literature review provided additional evidence of a potential relationship between a small number of cases of adult-onset psychosis and later Frontotemporal Dementia. However large prospective cohort studies would be beneficial to test this relationship (Velakoulis et al, 2009). In a 5 year follow up of 239 people over the age of 65 with Mild Cognitive Impairment and 119 people with Mild Behavioural Impairment, the latter group were found to convert to dementia in 70% of cases, the most common being Frontotemporal dementia. 34% of the Mild Cognitive Impairment group converted (Taragano et al, 2009).
The authors of a genome search meta-analysis of familial late-onset Alzheimer’s Disease identified a linkage with regions on chromosomes 1, 7 and 8 (Butler et al, 2009). Incidence of dementia was not found to be increased among 2286 atomic bomb survivors compared to a control group (Yamada et al, 2009). The authors of a meta-analysis of longitudinal epidemiological studies of risk factors for Alzheimer’s Disease identified obesity and diabetes as independent risk factors (Profenno et al, 2009). There is evidence that Zinc acts as a ligand at the metabotropic receptor (Besser et al, 2009). The authors of a retrospective post-hoc study of Galantamine concluded that the optimal dose in mild Alzheimer’s Disease was 16mg/day (Aronson et al, 2009). Elevated antibodies to helicobacter pylori were found in the CSF of people with Alzheimer’s Disease (n=27) compared to age-matched controls (n=27)(Kountouras et al, 2009).
The Swedish Lund group have suggested an aggregate of MMSE scores, clock drawing test and 3D cube-copying test scores as indicating a further exclusion of Lewy Body Dementia on the basis of this study of 33 people with Lewy Body Dementia (Palmqvist et al, 2009). In a study of 21 people with vascular dementia, 79 people with AD and 352 controls there was found to be no significant difference between VaD and AD subjects on tests of prospective and retrospective memory (Livner et al, 2009). A significant difference in cognitive profiles was found between people with mild AD and subcortical ischemic vascular dementia. In this study people with subcortical vascular dementia scored significantly worse on tests of visuospatial function and working memory (Kandiah et al, 2009). An association of Cerebral Amyloid Angiopathy with cerebral infarction and haemmorhage was inferred from a significant increase in silent white matter lesions compared to a control group without CAA (Kimberly et al, 2009). A case of angiitis is reported in association with Alzheimer’s Disease (Annweiler et al, 2008). In a prospective Swedish study homocysteine levels were significantly associated with Alzheimer’s Disease in women (Zilberstein et al, 2009). Hippocampal atrophy was associated with a significant increase in the risk of progressive to dementia in 70 people undergoing Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease (Aybek et al, 2009). In a prospective study of 67 people with Multiple Sclerosis and 28 controls, active inflammation was associated with neurodegeneration but the inflammatory response diminished in the later stages of the disease until neurodegeneration occurred at a similar rate to the control group (Frischer et al, 2009).
A widely reported study in the Journal Neuron has shown that different types of dementia including Alzheimer’s Disease and behavioural variant Frontotemporal Dementia exhibit degeneration along neuronal networks and that the network is specific to the type of dementia. The researchers used MRI BOLD imaging which gives an approximation to regional cerebral blood flow. A pilot study of a drug CPHPC has shown that it is effective in lowering the levels of serum amyloid P component (SAP) in the blood and the brain of people with Alzheimer’s Disease although follow-up studies will be required to assess the clinical implications (also reported here). An intriguing link has been found between proliferator-activated receptor coactivator 1 (a risk factor for diabetes type 2) and Alzheimer’s disease. The study shows that the gene product was decreased in Alzheimer’s Disease and may be related to processing of the Beta-Amyloid plaque. While diabetes is associated with a 2-fold increase in dementia prevalence, this study shows the heterogeneity that exists in the relationships between these two complex disorders. Episodes of hypoglycaemia were associated with an increased prevalence of dementia in this study. A new model of Alzheimer’s Disease has been developed and simulated on a computer. The model focuses on the the formation of the amyloid beta plaques and focuses on presenilin-1 and glycogen synthase kinase 3, proteins that have been implicated in Early-Onset Alzheimer’s Disease. The simulations suggests that neither protein results in disease alone but it is the combination which produces disease. Nevertheless such simulations may need to be followed up with biological studies to verify the predictions. The authors of a recent Cochrane review of relevant trials concluded that statins taken by study participants between the ages of 40 and 82 did not reduce the risk of dementia. The authors suggest that there may be different consequences for earlier administration of statins although that will require a further evaluation of relevant data. New evidence suggests that earlier experimental findings suggesting that the plaques in Alzheimer’s Disease produced calcium influx by thinning cellular membranes may instead have been an artefact produced by the use of a solvent in these studies – Hexafluoroisopropranolol. Research suggests that Huntington’s Disease is associated with a variety of changes (some of which related to glucose metabolism) that occur throughout the developmental period. Infrared tracking has been used to detect differences in duration of eye fixation on novel images in Mild Cognitive Impairment compared to controls which may have diagnostic utility.
A committee found evidence of an association between Agent Orange exposure in Vietnam war veterans and risk of developing Parkinson’s Disease based on an an analysis of 16 studies looking at the effects of the herbicides. The authors conclude however that other types of study are needed to examine this association in more detail. A new Xenon delivery system has been developed which may have benefits in protecting against hypoxia-induced brain injury in humans. A single-blinded study (n=78) looked at improving attention (4 types described) in people who had developed a stroke by using Attention Process Training. Although they did find an improvement in attention with this training, at 6-months.
In a rather ingenious study (which is open access and freely available here) cognitive impairment and depressive symptoms were assessed in 16,800 participants in a cohort study and the results were correlated with data on ‘two-week average sunlight exposure’. The researchers did find a significant association between cognitive impairment and the sunlight exposure so it will be very interesting to see if this is replicated and if so how such a relationship might be working. In another study published in the Proceedings of the National Academy of Sciences, alpha-synuclein has been found to be transmitted from one cell to another within cell cultures and there was further supporting evidence for such an association and this has implications for therepeutic approaches in Parkinson’s Disease and related conditions. In a structural MRI study looking at 679 people (>=65 years) there was found to be an increased association between memory impairment and white matter hyperintensities and also an association between strokes and non-memory cognitive impairment which remained after correction for factors such as APOE4 status and age. The authors of a PNAS study demonstrated increased toxicity associated with increased size of ABeta dimers that constitute the ABeta plaques. In a prospective longitudinal study of 1880 New York community dwellers there were found to be significant associations between consumption of a Mediterranean diet, exercise and a reduction in the prevalence of dementia. The authors of one paper examine the hypothesis that the Raphe nuclei might be an important component of the pathology of Alzheimer’s Disease (Simic et al, 2009). Further evidence for a link between Frontotemporal Dementia and Amyotrophic Lateral Sclerosis (ALS) has been found in a post-mortem study where the FUS (fused in sarcoma) protein (associated with ALS) was found in the neuronal inclusions in 15 people with frontotemporal dementia (Neumann et al, 2009). An analysis of the data from the Alzheimer’s Disease Neuroimaging Initiative provides further support for the hypothesis that conversion from Mild Cognitive Impairment to Alzheimer’s Disease is strongly influenced by Medial Temporal Lobe volume and particularly the volume of the hippocampus (Risacher et al, 2009). A small study involving 34 people without evidence of cognitive impairment, at post-mortem found a significant correlation between performance on a smell test (the Brief Smell Identification Test) and Alzheimer’s Disease pathology (Wilson et al, 2009). The smell test however can be influenced by smoking.
An in-vivo study has provided evidence that Dimebolin has a high affinity for the Serotonin 5HT6 receptor in vivo (Schaffhauser et al, 2009). Dimebolin under the name Dimebon was trialled in Alzheimer’s Disease and showed promising results. There may be a focus on this receptor for therapeutics if these results are replicated. In this article, there is coverage of a prospective cohort study in Honolulu which includes post-mortems to clarify the processes leading to the dementia. The study has been going on for many decades and the researchers have now accumulated data from close to 800 autopsies and are able to compare this with neuropsychological and other data. NHS Choices discuss a study involving Olive Oil and finding that it binds to A Beta-derived diffusible ligands (ADDLs) and influences in turn their binding to synapses which may have implications for the disease process in Alzheimer’s Disease. In America, a group of neurologists have developed consensus guidelines for the use of cognitive enhancers in adults without dementia. Another study involved contacting retired American Football (NFL) players and conducting a survey over the phone. The researchers found a much higher prevalence of dementia in the NFL players than the national average.
Using an analysis of EEG data from patients with Frontotemporal Lobar Degeneration and Alzheimer’s Disease, a team has found further evidence that in Alzheimer’s Disease there is increasing disconnection between areas in the brain. However they found that communication between areas became more structured in people with FTLD. The findings are relevant in terms of a disconnection hypothesis which maintains that in Alzheimer’s Disease there is a loss of function resulting from impaired communication between brain regions. A research team in Germany have provided evidence of ferritin in neurons in Parkinson’s disease. Iron metabolism has been implicated in the disease process and previous research has identified the ferritin in the glial support cells (see also this article in which the Diamond Light Source Synchrotron is being used to examine iron distribution in Parkinson’s Disease). An Israeli study has provided preliminary evidence for the viability of mesenchymal stem cells (which means there is no need for embryonic cells) in a model of Huntington’s Disease. By ‘labelling’ the cells with iron particles they were able to follow their progress using Magnetic Resonance Imaging and observed them migrating to their destination. It will be interesting to see further use of this neuroimaging technique as well as the work with stem cells. In a study looking at the MECP2 gene (methyl CpG binding protein 2). A mutation in this gene results in Rett Syndrome, a developmental disorder associated with seizures and cognitive impairment. The research team looked at the gene and the surrounding DNA in a total of 940 people who were healthy or who had developed dementia or psychosis. They found that one specific allele of MECP2 was associated with a number of changes in the structure in the brain including a reduction in the surface area. They also found that variations in the surrounding region were associated with structural changes in the brain and this gene region may turn out to have an important developmental role. Another study provided evidence that formal education reduced the risk of Alzheimer’s Disease even if there was a reduction in brain volume. New drugs – ATPZ’s have been identified which prevent the formation of Alzheimer’s Disease tau protein clumping in vitro.
A German team have provided evidence that two Parkinson’s Disease associated genes – Parkin and PINK1 interact to maintain mitochondrial function and the researchers suggest that this may have implications for possible disease-modifying therapies. In a study of people who had developed concussion (20 subjects and 20 controls), neuropsychological testing identified executive impairment but CT and MRI scans did not pick up evidence of injury. However the researchers also used Diffuse Tensor Imaging and were able to identify areas of injury with particular involvement of the prefrontal cortex which was consistent with the neurospychology results. The researchers also found a significant association between the DTI identified injury and the executive performance and the research team suggest that this provides evidence for a role for DTI in concussion. One research team have used ambient background noise during training exercise to help people with Parkinson’s Disease learn how to speak louder as the condition can affect their expressive speech. The team is now looking to make small modifications to their approach. There has been confirmation of the efficacy of delivery of a gene for Nerve Growth Factor in a murine model of Parkinson’s Disease in one study. The gene was delivered using a modified Adenovirus and the expression of the gene was modified with Doxycycline. A large study provided some preliminary evidence of a relationship between increasing diastolic blood pressure and cognitive impairment in people over the age of 45. The study involved 30,228 subjects from the longitudinal REGARDS study (Reasons for Geographic and Racial Differences in Stroke) but the association here was drawn from cross-sectional data obtained from the cohort and so it would be interesting to see replication using longitudinal data and other cognitive measures that are used for assessment of mild cognitive impairment. One study looking at older adults (over the age of 70) (n=94) investigated the relationship between Body Mass Index and cortical volume as measured using tensor based morphometry. The researchers found a significant association between increasing Body Mass Index and a reduction in cortical volume and it would be interesting to see large replication studies.
A meta-analysis of prospective and case-control studies examining the relationship between smoking and Alzheimer’s Disease which adjusted for a number of factors including tobacco company affiliation of the studies showed that smoking was a significant risk factor for Alzheimer’s Disease (Cataldo et al, 2009). A post-mortem study comparing the brains of people who had Alzheimer’s Disease and hyperphagia with those who did not found a significant reduction in 5HT4 receptors in the former group (Tsang et al, 2009). A small study has provided initial evidence of a significant association between performance on a smell-test and response to Donepezil according to clinical impression in people with mild-to-moderate Alzheimer’s Disease. A study of young-onset dementia (n=235) found a high prevalence of psychiatric and behavioural disorders. A prospective study looking at people with Alzheimer’s Disease found a significant association between the use of antihypertensive medications and a lower rate of cognitive decline and higher MMSE scores at baseline even after controlling for blood pressure.
The authors of a Cochrane review of the use of PEG feeding in advanced dementia found no randomised controlled trials and concluded that there was no evidence to suggest improved survival or quality of life although one of the authors, Dr Sampson points out that cases are assessed individually while also noting assisted oral feeding as an alternative approach. The authors of a recent report looked at studies involving non-pharmacological approaches to managing Alzheimer’s Disease and found evidence of benefits for caregiver training and cognitive training although concluding that methodologies for these studies needed to be improved. APOE4 carriers aged 20-35 were found to have different patterns of activity in the hippocampus compared to controls using fMRI although longitudinal studies will likely be needed to examine the clinical relevance of these findings. Problematic behaviours were identified in a Mayo Clinic study in one sixth of people with Parkinson’s Disease prescribed medication for their condition. A Lilly-funded study has provided evidence that a new technique known as Stable Isotope-Linked Kinetics is effective in identifying rates of A-Beta production which could be effective in identifying new therapies in Alzheimer’s Disease. There is evidence that Amyloid Plaques in Alzheimer’s Disease may produce synaptic damage by a mechanism which involves free radical production and the mitochondrial protein DRP1. Maintaining a focus on the external environment improved posture in Parkinson’s Disease in one study.
An intriguing finding is that proton pump inhibitors such as omeprazole have been shown to reduce the inflammatory response of microglia and the authors speculate as to whether this might impact on conditions such as Alzheimer’s disease which would need further investigation. Humanin peptide which has a role in cell death has also been found to strongly influence glucose metabolism offering a potential link between glucose metabolism and neurodegenerative processes. A prospective study showed evidence of an increased association with Alzheimer’s Disease in ‘heavy’ users of NSAID’s which have previously been suggested to have a protective effect. Stigma and perceptions about memory were found to influence memory performance in older adults in this study. A small study of people with Alzheimer’s Disease (AD) compared with people with mild cognitive impairment and healthy controls (n=55) provided evidence that there was a correlation between the PET and CSF markers of ABeta but that they did not correlate significantly with cognitive impairment (Jagust et al, 2009).
A study in Nature Neuroscience suggests that Amyloid Beta is integral to memory function and that deviation from optimal levels is likely to lead to pathology. This in turn would suggest that removing Amyloid Beta from the plaque may not be a successful strategy in Alzheimer’s Disease if this optimal level is not addressed. However this discussion is taking place around cellular mechanisms and it will be useful to see how these predictions tie in with the relevant clinical trials. A suggestion has been made that a precursor to Nerve Growth Factor may be involved in the pathogenesis of Alzheimer’s Disease (AD) on the basis of a significant increase in the levels of the precursor in AD post-mortem samples and findings in a murine model. Stroke is related to dementia in a number of ways and modifying stroke risk factors can reduce the risk of dementia. Thus a prospective study (n=3298) with a follow-up period of 9 years showed that moderate or heavy exercise was asssociated with a significantly reduced risk of developing stroke. Thus the risk was 2.7% in those with moderate-to-heavy exercise and 4.6% in those with no exercise. A potentially very useful study used the Alzheimer’s Disease Neuroimaging Initiative dataset to develop a method of analysing MRI data which involves two scans and a focus on loss of tissue in the Entorhinal Cortex and it will be intereresting to see the results of further research in this area. A 32-year prospective study – the Prospective Population Study of Women in Gothenburg found an association between central adiposity in middle age and prevalence of subsequent dementia. They did not find the same relationship between BMI and subsequent dementia but the central adiposity was associated with an approximate doubling of the prevalence of subsequent dementia.
Three genes associated with Alzheimer’s Disease were identified in 2 studies published in Nature Genetics. Amouyel and colleagues conducted a two-part study (Amouyel et al, 2009). In the first part of the study they undertook a Genome-Wide Association Study involving 537,029 single nucleotide polymorphism’s (SNP’s) in a French sample of 2032 people with Alzheimer’s Disease and 5328 controls.As there were multiple comparisons, they needed to control for this (with a Bonferroni correction) and a marker in the CLU gene on chromosome 8 (8p21-p12) showed a statistically significant correlation just above the threshold.
They then attempted a replication in the second stage which involved 3978 probable cases of Alzheimer’s Disease and 3297 controls. This second stage involved subjects from Spain, Belgium and France. They confirmed a statistically significant association of CLU with the probable Alzheimer’s Disease subjects and additionally found a significant correlation with CR1 on chromosome 1 (1q32). The researchers then estimated the contribution of each gene to the risk of Alzheimer’s Disease and estimated that the attributable risk for APOE (a well established risk factor for Alzheimer’s Disease) was 25.5%, for CLU it was 8.9% and for CR1 it was 3.8%. Nevertheless the CR1 did not show up in the first stage of the study.
In the second study, Professor Julie Williams and colleagues (including Professor Michael Owen) undertook another two part study. This involved ‘up to 19,000 subjects’ in the initial stages of the study, these subjects being recruited from Europe and the United States. Again, this was a Genome Wide Association Study. After quality control measures, they looked at 529,205 autosomal single nucleotide polymorphisms in 3,941 people with Alzheimer’s Disease and 7,848 controls. They identified one marker in CLU (the same gene identified in the study above) and a second in the PICALM gene on chromosome 11. Importantly both of these findings were replicated in the second stage of the study which involved 2,023 people with Alzheimer’s Disease and 2,340 age-matched controls.They then looked further to see if they could identify which areas within the gene were significantly correlated and produces some candidate regions. The team point out that there are other significant genes which wouldn’t have been identified in this analysis.
Thus the three identified genes were CLU, PICALM and CR1.
The CLU gene (Clusterin) which was identified in both studies encodes an apolipoprotein which together with APOE is found in the central nervous system as well as other tissues. There are many suggested pathways for the involvement of CLU in the pathology of Alzheimer’s Disease. Thus CLU is found in the amyloid plaques found in Alzheimer’s Disease and there is evidence also suggesting that it may be involved in the removal of Beta Amyloid from the brain (by forming soluble complexes which can cross the blood brain barrier) and may play a role in inflammation in the brain.
The PICALM gene which was significantly associated with Alzheimer’s Disease in the second study encodes a protein that is involved in endocytosis. Mutations in PICALM (phosphatidylinositol-binding clathrin assembly protein) may therefore interfere with the transport of materials into the neurons and the team suggest that synaptic vesicle cycling may affected (for another study looking at vesicle cycling see the study below which involved a newly discovered protein – the Flower protein which may be involved in Calcium regulation within the neuron emphasising the importance of endocytosis in neuronal functioning).
The CR1 gene which was significantly associated with Alzheimer’s Disease in the second stage of the first study, encodes a receptor for C3b protein. The C3b protein forms part of the complement cascade and again there is some evidence suggesting that it may be involved in the removal of Beta Amyloid. The CR1 receptor may be involved in the process of phagocytosis – when material is ingested by the immune cells. In analysis of data from the Maastricht Aging Study, 35 healthy older adults without cognitive decline were compared with 30 older adults who displayed cognitive decline (using thresholds on several outcome measures) and in the latter group there was found to be a significant reduction in grey matter volume in the hippocampus, hippocampal gyrus, frontal and cingulate cortices. Now that these gene associations have been identified it will be interesting to see further replication studies as well as studies examining the possible roles of these genes in further detail.
The N60 region of the RanBP9 protein has been associated with an increased production of Beta-Amyloid production using post-mortem and cell culture data and these findings may lead to the development of novel therapeutic interventions for Alzheimer’s Disease. This protein binds to another protein which is involved in the movement of RNA through the pores in the nuclear membrane. RanBP9 interacts with several other proteins also. A new finding reported in the journal Cell is that cells are able to move using a newly identified mechanism which involves a folding of the membranes to form filopidia and this involves the use of a protein sRGAP2 which is associated with neurodevelopmental disorders. This may have important implications for the understanding of neurodevelopment.
Predicting which people with Mild Cognitive Impairment go on to develop dementia is an area of current research interest. There are many studies using different methodologies looking into this question. One predictor is that the size of the Hippocampus (size is inversely correlated with dementia risk) which has a robust evidence base. However, a recent study provides evidence that financial skills may be another marker of risk and this has been widely reported in the media (e.g. here, here and here). A research team, just published in ‘Neurology’ found that people with Amnestic Mild Cognitive Impairment who scored poorly on the Financial Capacity Instrument were more likely to develop dementia. The sample group were people with Amnestic MCI and are therefore already a select group who have been assessed as having formal difficulties with memory. They were being scored on a tool which measures financial skills. The size of the study is relatively small (n=163) and of these, 25 people with Amnestic MCI went on to develop dementia.
There was found to be a significant association between a variant in the gene LINGO1 and Parkinson’s Disease and Benign Essential Tremor suggesting that this gene may be involved in both conditions. The gene variant is identified with approximately 5% of people with either condition. A gene sequencing process mrFAST (micro-read Fast Alignment Search Tool) has demonstrated utility in detecting duplicated genome sequences and the researchers have noted an increased number of copy number variants in genes which are located in a segment of the genome which underwent significant duplication in the ape/human ancestor. The process has implications for detection of diseases in which copy number variants need to be estimated and has also been used in the 1000 Genome Project. Alz Forum have got coverage of the recent Clinical Trials in Alzheimer’s Disease conference in Las Vegas here. They look at the Wisconsin Registry for Alzheimer’s Prevention study, the Memory Capacity Test and research on the CogState test amongst others.
Two compounds have been identified which modify the action of insulin-degrading enzyme on A-Beta offering another potential therapeutic approach in Alzheimer’s Disease. A prospective California study with 9000 subjects provided evidence of an association between higher levels of cholesterols in people aged in their 40’s and the subsequent prevalence of Alzheimer’s Disease in their 60’s to 80’s. The article is freely available here. Analysis of the data from the Nun study continues with over 500 brains obtained post-mortem. The Nun study followed up several hundred nuns, examining a large number of factors and identifying associations with Alzheimer’s Disease. In this article you can watch an interesting video containing interviews with some of the nuns as well as a post-mortem dissection of a brain with enlarged ventricles. The Nuns have been very generous in ensuring that their brains can be used for research after their death and this type of research is very important in coming to a better understanding of the disease process. In a study of people with Parkinson’s disease using a driving simulator and comparing this group to age-matched controls, the Parkinson’s subjects were significantly more likely to experience a crash under low visibility settings than the control group. There were a number of factors including visual processing speed which were significantly associated with driving performance in the simulator. A phase 1 clinical trial is currently underway to examine the potential neuroprotective role of the antibiotic Minocycline in acute ischaemic stroke.
Research in Child and Adolescent Psychiatry
In a Norwegian twin study involving 712 adults, childhood separation anxiety disorder, CO2 hypersensitivity and adult panic disorder were influenced by a single variable which in turn was determined mainly by genetic factors. A prospective cohort study of 1037 children followed into adulthood found that lower IQ was a predictor for depression and anxiety in adulthood, whilst higher IQ was a predictor for adult mania. The authors recommend that this information is utilised in service development. In a study which looked at MRI scans of three groups – children with ADHD treated with psychostimulants, children with ADHD not treated with psychostimulants and age matched controls – the hypothesis being tested was that psychostimulants would interfere with cortical development using cortical thickness as a marker. The findings showed however that the children with ADHD not treated with psychostimulants were characterised by a thinner cortex than the other two groups while the psychostimulant treated group did not differ from the controls contrary to the null hypothesis. In an fMRI study of four groups – boys with ADHD, boys with ADHD with hyperactive-inattentive subtype, boys with conduct disorder and age matched controls – there was found in the conduct disorder subgroup to be reduced activation during a sustained attention task, in the insular cortex, hippocampus and anterior cingulate cortex and cerebellum whilst in the ADHD group there was found to be reduced activation in the ventrolateral prefrontal cortex and increased activation in the cerebellum. In another fMRI study there was an association with a reduction in Amygdala activation in response to presentation of fearful faces in boys with conduct problems and callous-unemotional traits.In a longitudinal study of childhood temperament involving 12,150 people (with employment status at follow-up being identified for 7183) responses to the childhood questions ‘often complain of aches and pains’ and ‘often appears miserable or unhappy’ were significantly associated with middle age sickness absence after controlling for a number of other variables (Henderson et al, 2009). An association between the glucorticoid receptor and abuse in childhood has been shown in one study. At the AAAS meeting, a study of children in 50 familes was presented in which gesturing at age 14/12 was associated with a larger vocabulary at age 4.5 years. Further examination of an association between gesturing and vocabulary is of potential relevance to conditions where gesturing is reduced. Over 500 6-18 year-olds were scanned prospectively (using MRI) as part of the ‘NIH MRI Study of Normal Brain Development’. A significant association between cortical thickness in multimodal association areas and intelligence was found. There is a study showing that having extra copies of the LIS1 gene may result in changes in neural development and is associated with learning disability in children. When the LIS1 gene is missing, lissencepaly results. Preliminary results suggest that game playing robots that respond to physiological data are associated with a number of positive outcomes in children with Autistic Spectrum Disorders. Having extra-curricular activities at school was associated with more years of education in later life. In a test of attention, the Visual Serial Addition Test, children with ADHD were found to have similar accuracy of responses to the control group but higher variability in response times. A lack of a morning rise in cortisol in children with Asperger Syndrome is suggested as a potential contributor to their clinical presentation. 5 single nucleotide polymorphisms of transthyretin (which inhibits amyloid beta protein production) were associated with significant hippocampal atrophy (Cuenco et al, 2009).
A neuroimaging study (n=88) compared people with Asperger Syndrome and Autism with controls and found a significant difference between the Asperger and Autism groups in terms of structural MRI findings with the latter group having increased grey matter volume in the frontal and temporal lobes (Toal et al, 2009). However it will be interesting to see this data be included in a meta-analysis with other similar studies as well as to see the findings of larger replication studies. This study is timely given the recent discussion about dropping the diagnosis of Asperger Syndrome (see below). A study of children’s moral values in the real world and also in virtual worlds provided some complex results including an association between moral values in both environments. Hypertension in children was associated with impairment on a number of cognitive tasks consistent with findings in adults. High-angular resolution diffusion imaging was used in twins to suggest that genetics determine myelin integrity in a number of important brain regions. Since myelin influence nerve conduction velocities and this is associated with speed of processing which in turn is associated with intelligence, myelin genes have been suggested to be related to intelligence. A Finnish group has been characterising a subgroup of children with delayed speech and walking and it will be interesting to follow further research in this area. A Canadian study provides evidence of an association between perinatal factors and the comorbidity of ADHD and Tourette syndrome. In a presentation at the Annual Convention of the American Psychological Association, a recommendation has been made for managing childhood obesity by encouraging positive body image and exercise in children.
Research in Learning Disability
In a large study which involved the use of 11,700 questionnaires for primary school children and the use of the Special Educational Needs register (and ICD-10 research criteria) in Cambridgeshire, the authors produced a revised prevalence estimate of 157 cases of autistic spectrum disorder in every 10,000 (Baron-Cohen et al, 2009).
Research in Liaison Psychiatry
A case-control study of 113 people with Chronic Fatigue Syndrome (CFS) and 124 controls showed a 6-fold increase in Chronic Fatigue Syndrome with self-reported childhood trauma. CFS was more likely if there was PTSD in addition. Childhood adversity and anxiety or depression were independently associated with adult-onset headaches in a study which pooled data from cross-sectional surveys in several continents (n=18303). The results of longitudinal studies in this area will be interesting to see. In another study there was found to be a similar prevalence of Chronic Fatigue Syndrome in Brazil and Britain although it was underdiagnosed in comparison in Brazil. The authors conclude that cultural factors may contribute to recognition of the illness by doctors. PTSD was found in more than 1/3 of people who had experienced a stroke and this this influenced recovery.
In a systematic review which included 27 studies comparing medical care in those with mental illness and 10 in those with substance misuse versus a control group the results were heterogenous. Some of the studies showed evidence of decreased medical care while others showed improvement in some areas (Mitchell et al, 2009). In one study nearly 93% of people with SLE were found to psychiatric conditions including anxiety and depression while in another study 63% of people with Rheumatoid Arthritis were found to have psychiatric conditions predominantly depression and as with previous studies was associated with the characteristics of RA.
Research in Neurotic, Stress-Related and Somatoform Disorders
In a study which looked at 532 Norwegian people who had experienced the 2004 Tsunami in South-East Asia, the authors repeated measurements of the perceived life threat using a 5-point Likert scale which appears to have been designed for use in this study and which appears to have been validated within the study by correlating with other measures of danger perception. The authors describe an effect they refer to as recall amplification whereby the perceived threat of the original event increased with time. The authors conclude that their data suggests the current diagnostic criteria for PTSD should be reconsidered particularly as the recall amplification occured independently of the type of events or severity of PTSD symptoms* (Heir et al, 2009). The authors of a Cochrane review concluded that preventive psychological intervention (CBT and counselling) after trauma may not prevent onset of PTSD symptoms. This study was looking at prevention rather than treatment of PTSD. However in treatment of PTSD there is a good evidence base for psychological treatments.
Research into Eating Disorders
A retrospective cohort study of Swedish women treated for anorexia in an inpatient setting showed a Standardised Mortality Ratio for all causes of death of 6.2. The authors caution that as treatment was in the inpatient setting it was likely to represent more severe illness. The risk was still elevated some 20 years after the initial admission although this decreased over time.
Research In Substance Misuse
Research showing that mortality rates from alcohol in men are twice those of women in Scotland. A new study shows that the enzyme P4503A is unlikely to be involved in the clearance of methadone. There is evidence of a unidirectional relationship between alcohol and depression – with the authors concluding that alcohol abuse or dependence leads to depression rather than the reverse. Increasing age was associated with a greater impairment in planning and motor coordination and decreasing insight into these impairments after drinking alcohol. Portrayal of alcohol on TV adverts and films was found to have an immediate effect on drinking behaviour in viewers in this study. In a group of people with the inactive form of Alcohol-Dehydrogenase 2 (associated with adverse responses to alcohol), high novelty seeking and low harm avoidance traits were associated with alcohol use. Indirect evidence suggests that low-moderate levels of alcohol influence the release of beta-endorphins in the ventral tegmental area. A poll of 2000 people in England showed that many people are unaware of the calories contained within alcohol as reported here. A study has shown that cessation of drinking significantly influences survival rates in cirrhosis of the liver – for those continuing to drink – survival rates at 7 years was 44% compared to 72% in those who were abstinent.
A Portuguese study has found that the two leading cause of alcohol related mortality are liver disease and car accidents. Research has further supported the association of the MPDZ and alcohol dependency. An M1 Acetycholine agonist has been recently discovered. Over 3000 genes that are differentially expressed within a 24-hour period have been identified. An increase in the number of neonates born with withdrawal syndrome has been reported in this Australian study – a 40 fold increase from 1980. A recent Cochrane review looked at interventions for reducing alcohol misuse in university students and the authors examined 22 controlled trials with a cumulative total of 7275 college students finding that web-based/computer feedback was associated with a significant reduction in a number of outcome measures including drinking frequency, quantity, binge drinking and peak blood alcohol content. Patterns of substance misuse are being studied in Oregon, USA by analysing waste water before it is treated. The BMA has released a new document on ‘the effect of alcohol marketing on young people‘ and there has been wide reporting on this in the media.
With increasing numbers of under-18 drinkers in the UK developing liver disease and being admitted to hospital, the charity Alcohol Concern has called for an increase in the pricing of drinks. An American study has provided evidence that Alcohol adverts on cable television have a significant correlation with the likelihood of teenager viewing of the cable TV. They found that wine adverts were inversely correlated with an increasing percentage of teenage viewers in the audience but that there was a significant linear correlation with spirits, low-alcohol ‘alco-pop’ drinks and beers. This is interesting in relation to older studies which show that teenagers with ‘media resistance skills‘ in another american study were less likely to drink alcohol. Earlier this year an Australian study provided evidence that adolescents there were seeing more alcohol-related adverts and the authors recommended a move towards regulation of adverts. Using data from the National Epidemiological Survey on Alcohol and Related Conditions, an american study involving data on 43,000 people, older adults (over the age of 60 in this study) with alcohol dependence consumed an average of 40 alcoholic drinks per week compared to ‘between 25 and 35 drinks a week’ in the younger group.
Miscellaneous
There is a commentary in the American Journal of Psychiatry about publication bias and the effectiveness of antidepressants partially in response to the Kirsch study and following another editorial in the British Journal of Psychiatry. A recent study looking at dreams is discussed here in more detail. The study looked at cultural differences in dreams and the researchers also found that people were more likely to think the dreams related to their life if it was consistent with their beliefs. A recently extinct species, the Pyrenean Ibex has been cloned (using DNA from skin samples) after the eggs were introduced into a goat. Unfortunately the infant died soon after birth. This will surely trigger an ethical debate while at the same time offering an option unthinkable to conservationalists even a decade ago as well as having ramifications across the life sciences. A study has provided evidence of a possible association between a virus XRV and Chronic Fatigue Syndrome.
A recent study looking at the effect of Beta-Blockers on emotionally disturbing memories in Nature Neuroscience is discussed in more detail here. There were a number of recent studies with findings relating to the Insular Cortex. In one study, regional cerebral blood flow in the right Insular Cortex decreased at 30 minutes after exercise and the authors argue for an association with exercise induced decreases in blood pressure (Williamson et al, 2009). In a post-mortem stereological study at the end of last year, involving 15 people with schizophrenia, 15 with unipolar depression and 15 with bipolar disorder as well as 15 controls there was found to be a significant decrease in neuronal volume in layer 2 of the Insular Cortex in schizophrenia. The authors recommend further work to expand upon these findings in schizophrenia (Pennington et al, 2008). A longitudinal (4 years) MRI study in 23 people with first episode psychosis, 11 people with chronic schizophrenia and 26 controls showed that significant grey matter reduction in the insular cortex of the people with first-episode psychosis relative to controls (1 year v 4 years). Furthermore there was a correlation between loss of grey matter volume in the left insular cortex and positive and negative symptoms. Both people with first-episode psychosis and schizophrenia had a significant reduction in grey matter volume in the anterior insular cortex (Takahshi et al, 2009).
In a study of residents in long-term care who were referred for psychiatric assessment (n=868) there was found to be elevated Thyroid Stimulating Hormone (TSH) in 10.8% of people and a significant association of elevated TSH with female gender (Sabeen et al, 2009). The authors of a systematic review looked at services providing acute time-limited residential alternatives to inpatient psychiatric ward treatment for people needing acute admission. The authors described their search strategy and were able to identify 27 studies for inclusion in their review. They assessed the quality of these studies and found that a number of the studies didn’t conceal allocation of subjects or adjust for confounders although they did provide evidence of outcomes comparable to acute inpatient treatment in a number of studies. The authors concluded that more research was needed in this area although there was ‘preliminary evidence’ to support the community-based alternatives examined (Lloyd-Evans et al, 2009).
One study was particularly interesting in terms of methodology. In this study, outpatients in a substance misuse service used ‘ecological momentary assessment’ (EMA) to report their mood, exposure to drug-use triggers and craving. The assessment was completed by utilisation of a handheld device. Another technique was developed which is thought to have a saved a considerable number of lives in surgery. In the World Health Organization’s Safe Surgery Saves Lives program, a 19-point surgery checklist was associated with a reduced rate of death from 1.5% to 0.8% in 3733 non-cardiac surgical operations before the checklist was introduced and 3955 operations after the introduction of the checklist. Whilst not directly related to psychiatry (except in the case of psychosurgical operations) this research shows the important benefits of process. Ethicists are joining ward rounds over in the United States where they contribute to the decision making processes in complex cases.
The authors of a meta-analysis of six studies looking at the epidemiology of ADHD concluded that the prevalence decreased with increasing age but there were difficulties with the DSM-IV criteria in adulthood for a number of reasons. For instance although there were fewer symptoms in adulthood, people still met criteria for functional impairment (Simon et al, 2009). A study looking at how people responded to exposure to the traumatic events (such as 911) covered in the media and finding that people had many helpful ways of coping. This research showed benefits of dextroamphetamine in speech processing in Broca’s Aphasia. This is interesting in relation to the treatment of thought disorder using antipsychotic medication. A small study examined the association between anxiety levels in jurors and the nature of material being discussed in the trial and suggested that women could be more prone to anxiety in the trials particularly if they had experienced similar events in their own history. However further replication is needed. There is evidence suggesting is that GTF21 is associated with social behavioural performance and GTF2IRD1 is associated with visuo-spatial performance in Williams Syndrome. There is evidence that a protein, Nup214, regulating passage of material through the nuclear pore complex plays a role in unpacking RNA.
Genetic variations in a specific amino acid coded for by the HLA-DRB1 gene has been associated with susceptibility to Multiple Sclerosis. Elucidating the interaction between rhodopsin and transducin in visual processing in the retina. A very interesting finding was reported on suggesting that during an infection, a reticular network is laid down in the brain which guides immune cells. The recent construction of a connectome suggests that genetics play a small role in the formation of connections in the nervous system.. A recent study looks at the complex impact of online publications. An imaging study showing an association between activity in the insular cortex in response to near misses in a gambling task and scores on a questionnaire indicative of problem gambling. A study showed a reduction in functional impairment following a CVA, with the use of tPA. An fMRI study suggesting that exercise modifies visualisation of cigarettes in smokers.
An increase in Ghrelin and a decrease in Leptin were found in people with chronic insomnia in this study. An association has been found between the metabotropic glutamate 5 receptor and the process of adapting to new changes in the environment. A study using photographic negatives has shown that contrast around the eyes is important in recognition of faces. Alpha activity was significantly higher before mistakes were made in a sustained attention task and this information has the potential to be used in jobs which require prolonged attention. Regulation of blood flow through cerebral arteries could allow perfusion of tissues after a stroke. Excessive daytime sleepiness has been associated with increased cardiovascular mortality in the elderly. Watching a speaker’s lips and face during speech was associated with up to a six-fold increase in comprehension. The number of years of music experience of musicians was associated with their ability to identify ‘emotion sounds’ in a study which compared musicians and non-musicians. Doodling was associated with a better retention of information when listening to a telephone message. There was an association between ‘positive emotions’ and better physical health reported on here. Religious believers were less likely to show activity in the Anterior Cingulate Cortex during a stroop test than non-believers in this study. In one study, subjects were found to be optimistic in predicting their performance on tasks in an ‘ideal world’ but their predictions were more realistic if they were asked how they were likely to perform without reference to the ‘ideal world’.
One study has looked at how scientific knowledge increases by focusing on yeast research. The researchers found that knowledge grew exponentially and that scientists (both junior and senior) working in large teams were less ‘productive’. The authors of an analysis of 57 prospective studies involving 900,000 people conclude that moderate obesity (BMI 30-35) reduces lifespan by an average of 3 years and severe obesity (BMI 40-50) reduces lifespan by an average of 10 years. QTC intervals have been used correlated with post-CVA mortality in one study. Cells derived from a tumour have been used to create neurospheres which are now being used in neuroscience research. The SIRT1 gene and NAD a metabolite for energy production have been linked in a new study. NAD is needed for SIRT1 function and levels of NAD in cells oscillates daily. SIRT1 is conserved across organisms and is implicated as a contributing factor in the aging process. Synchronisation of EEG activity was found in guitarists playing music together. A preliminary study suggests that Trigeminal Nerve Stimulation may be effective in intractable epilepsy.
A study providing different lines of evidence suggesting that President Obama’s presidential campaign has been correlated with a reduction in racism. A study showing that natural sounding sentences with false statements elicited larger evoked response potentials than similar sentences without false statements. A study found evidence that preschool children were able to recognise and follow consensus. A study has looked at a technique referred to as ‘dialectical bootstrapping’ in which evidence is provided that this improves the accuracy of decisions made by an individual. A study looking at learning in school in children born prematurely (before 26 weeks) is covered here. A study found that higher IQ was associated with lower risk of death from a number of conditions including coronary artery disease and that this could be explained through a number of factors including lifestyle (diet, exercise, smoking). The authors of an fMRI study suggest from their results that the Amygdala and Posterior Cingulate Cortex are involved in the decision making process of forming first impressions of another person.
A study in 34 people undergoing neurosurgical ablation of regions in the prefrontal cortex found evidence of social and emotional deficits on the ’social-emotional questionnaire’ (Bramham et al, 2009). A Canadian study which used data from the Canadian Community Health Survey looked at medication adherence in 6201 people prescribed psychotropic medication and estimated that non-adherence was 34.6% for antipsychotics and 45.9% for antidepressants and that the most frequent reason given was that of forgetfulness which also varied between the different types of psychotropic medication (Bulloch and Patten, 2009). A proposal has been made to create a map of mammalian brain circuitry. A protein Nurr1 was found to be involved in modulating the inflammatory response of microglia through a specific pathway and this response might be important in neurodegenerative processes. In the moderate stages of semantic dementia, a recent study provided evidence that autobiographical memory is impaired regardless of recency. Improved research methodology has been recommended for studies looking at delivery of psychological therapies in older adults. Another study in the BMJ and reported on here suggests that elderly people with strokes are undertreated. An association was found in an MRI study between aspirin and cerebral microbleeds in the elderly and this relationship will need to be explored in more detail given the various benefits associated with aspirin use. In another study, a trademarked system was effective in improving the dysarthria that developed after a stroke. A new type of shunting system is being developed following research into the flow of cerebrospinal fluid and this should have implications for hydrocephalus and a number of associated conditions. There is indirect evidence that Indoleamine 2, 3 dioxygenase may play an important role in the onset of depressive symptoms in chronic inflammation.
Exercises have been developed with reduced risk for aggravating migraines. Naltrexone has further evidence of benefit in people with kleptomania in one study. Developing depression after an initial diagnosis of coronary artery disease was associated with a 2-fold increased risk of heart failure in this study with an average follow-up period of 5.6 years. A study has shown that synchronisation between breathing and heart rate alters in different stages of the sleep cycle and the techniques used in this study could be used in future sleep research. The structure of a plant protein similar to that of mammalian proteins involved in circadian rhythms has been identified with potential implications for therapeutic approaches to sleep disorders. In fruit flies, sleep deprivation was associated with a build up of a synaptic protein known as Bruchpilot (BRP) and this might well generalise to humans although further research will be needed. Sleeping less than 5 hours a day was associated with a 500% increase in the risk of hypertension compared to those who slept more than six hours. The authors of another study looked at the interaction between culture and mood and provided evidence that lowering mood resulted in stereotypical behaviour whilst exploratory behaviour resulted from elevating mood (mood was influenced by either music or modifying facial expressions). Increasing ‘mirthful laughter‘ was associated with an increase in HDL in people with diabetes. The authors of a systematic review of the use of music in coronary heart disease patients concluded that music was associated with a significant reduction in heart rate and blood pressure. Benzodiazepine use in people in the Intensive Care Unit has been associated with the subsequent development of depression.. Family therapy was associated with higher response rates in people with depression when compared with treatment as usual. A specialised visual training method known as eccentric training (which involves the use of peripheral vision) has been advocated for use in people with macular degeneration. Long-term health goals were associated with higher levels of self-control in health tasks in this study. A review of previous studies suggests that several brain regions are associated with wisdom although definitions of this term vary. Older adults were found more likely to recover functioning after admission for surgery than for medical illnesses in this study although further replication studies will be needed.
Developments are underway in making Transmission Electron Microscope images of the brain and retina available to scientists around the world and also to integrate them into 3-dimensional models. The interaction of microglia with neurons has been published in a recent Japanese study in which it was found that microglia make contact with the synapses of a neuron regularly and for a usual duration of a few minutes. A number of studies have been presented at a meeting recently identifying a link between sleep disorders and risk of type II diabetes and obesity – and this is covered in more detail here. Similar research found that a 2.5 fold increased prevalence of diabetes II was associated with sleeping less than 7 or more than 8 hours a night which may be relevant to previous epidemiological data on sleep duration. There is evidence that neurons use proteins to fix the cell body to the extracellular matrix and then send out dendrites to target cells during development. A study of the offspring of centenerians (who would be expected to have similar longevity) were found to have low neuroticism and high extraversion. Acceptance and Commitment Therapy was found to be better than control conditions but not superior to other treatments in a meta-analysis of 18 studies A single intensive treatment for phobias which can last up to three hours was found to be effective in 55% of children in one study. Relationships formed in an online music community on the basis of shared musical tastes were found to be ‘fragile’ in one recent study. An interesting study provides evidence that we return our gaze to a previous target automatically unless we are actively searching from something (visually) in which case this action is inhibited.
Evidence is provided to suggest that the brain processes vowels and consonants at different rates. A computer-robotic system has constructed and completed an experiment in Yeast genes paving the way for a new generation of automated scientists to work alongside humans. A lack of supportive social relationships at work was associated with burnout in this Swedish study. Evidence suggests that women who were classed as obese were underrepresented amongst CEO’s of businesses compared to men which the authors interpret as suggesting weight discrimination against women although studies with different methodologies will be needed to explore this hypothesis further. Playing Baroque music at work improved the productivity and mood of radiologists in this study. There was evidence of a correlation between dopamine metabolism and reduced grey matter density in people with fibromyalgia compared to controls in a small case-control study. There have been similar studies of this type before, but this 5-year follow-up study of 1238 older adults provided evidence that having a purpose in life was associated with a 50% reduction in mortality. An interesting nurse-led study characterised qualitative aspects of relationships and other changes that occur in people after they have developed a stroke and more information can be found here.
In a 2009 sleep conference a number of interesting findings were reported. Evidence that a number of interventions were effective in insomnia including meditation and CBT was provided while under certain circumstances there was an association between certain types of television and gaming use and insomnia or sleep debt. In a small fMRI study, people with chronic insomnia were found to have increased levels of activation particularly in visuospatial areas compared to a control group when tested on a working memory task. In another study looking at adults with an average age of 40, less hours of sleep was associated with higher blood pressure. The researchers in a twin study found evidence that intrusive thoughts was associated with the stress-related insomnia. Increased sleep fragmentation was associated with a significant increase in mortality in this longitudinal study involving 5614 subjects. Older adults (aged 59-82) performed better than younger adults (aged 19-38) on cognitive tests after sleep deprivation in one study. From an evolutionary perspective there were a number of interesting findings that may be relevant to complex human phenomenon such as sleep. Thus in one study it was found that queen fire ants can sleep up to 9 hours a day whilst worker ants have small naps of up to a minute through the day suggesting a possible role for genetics in sleep patterns (although environmental cues may possibly play a role particularly as a recent study showed that ants respond to high pitched sounds which may be mimicked by other species and can produce marked behavioural responses). In another study it was found that rats were able to manage risk/reward so as to optimise reward in a task analogous to the Iowa gambling task. A study has recently provided preliminary evidence that paternal investment of resources (using a relevant outcome measure) is associated with the genetic similarity of the child.
One study provided evidence that naming objects may play a role in their perception. In this study people learnt how to group a novel class of object (designed for the study) based on similarities or name the objects. The latter group were better able to process new examples of these objects incorporating all of the features of this object much like one would with a face. More details are available here. In a prospective 5-year study of 906 older adults decreasing social activities (using a Likert Scale) were significantly associated with decreasing motor skills including strength and balance. A comparison of elderly people in the United States (from the Health and Retirement Study) and England (from the English longitudinal study of Aging) found that the American cohort performed significantly better on a number of cognitive measures than their counterparts in England. Members of the researcher team suggested that different treatment approaches to hypertension between the two countries may have contributed to these differences. The long and short versions of the period3 gene have been implicated in response to sleep deprivation and this study found that a different pattern of recruitment of cortical regions in a working memory task which the authors suggest as a potential intermediate step in the causal chain from gene to sleep deprivation response. A study has provided evidence that Amitriptylline binds to the tRKA and tRKB receptors causing dimerisation and results in outgrowth of neurites actions which parallel those of Nerve Growth Factor.
An MRI study (n=77 roughly) of people with dyslexia and a roughly equal number of controls without provided evidence of a difference between the groups in the right cerebellar declive and the right lentiform nucleus (the original article is freely available here). There have been previous studies which have implicated the cerebellum in language. The Canadian ‘Center for Addiction and Mental Health’ recently estimated that 1/25 of deaths globally are alcohol related (also covered here). Gaze is important in human social interactions and one study provided evidence that our interpretation of another person’s direction of gaze is influenced by our understanding of their internal state. These findings are relevant to social cognition theory. The authors of a recently published meta-analysis concluded that CBT was not effective in treatment of schizophrenia or in prevention of relapse in Bipolar Disorder and it will be interesting to see responses to this meta-analysis. A study provided evidence that people conceptualise objects that are grouped together as more likely to share similar properties. Subjects were more likely to choose from a widely spaced group if they knew one or more of the objects had defective parts and more likely to choose from closely grouped objects if they knew one or more contained gift coupons. Another study found that students were able to retain more information when presented with powerpoint slides without the use of animation to add information to the slide in stages.
In one study, students with higher levels of anxiety were found to spend more time focusing on irrelevant words (distractors) in a reading task. They were also given a maths task and it was found that the correct responses were similar in both the anxiety and control groups but the former group took longer to complete the tasks. (the article is freely available here). A slightly amusing finding occurred in one study looking at students who were using maths software packages for learning. When the students made mistakes they looked for problems with the computer software! In the National Longitudinal Study of Adolescent Health which included 2500 respondents there was found to be an association between carrier status for the MAOA low-activity-3-repeat allele and ‘gang membership’. It will be interesting to see the results of follow-up studies exploring this possible relationship further. In a study of violent recidivists, a lower glycogen level was associated with just under a third of the variation in recidivist offending. A systematic review of the cognitive effects of medications in older adults has been published. An online CBT package which utilises audio, visual and written material (but no clinician!) was used in one study in which participants enrolled for 5 weeks. 35% reported themselves as being ‘much or very much improved’. The authors of a expert-systems based computer program that generates music in response to the listener’s emotions are proposing to make the music copyright free (I haven’t yet been able to find the program online however and it looks as though it is in the prototype stage). It is tempting to speculate that such an approach could be adapted for therapeutic purposes for disorders of emotion and that absence of copyright fees might spur research in this direction.
An intriguing study with many ramifications involved looking at the effects of anger on measures of carotid artery flow in 3 groups of subjects of increasing age. The researchers found that anger was associated with vasodilation of the carotid arteries and that this effect did not occur in those with hypertension suggesting a possible mechanism for stress associated myocardial infarct. The authors of a recent survey of people who remained at home in New Orleans during Hurricane Katrina suggest on the basis of the results their decisions may be related to valuing a sense of community and that they did not view themselves as ‘powerless’. Repeating positive self-statements was associated with a decrease in self-esteem in those with already low self-esteem compared to those with high self-esteem in one study. The authors of a genetic study conducted in samples from a number of different ethnic groups have reported an association between perfect pitch and chromosome 8. A small fMRI study provided evidence of increased activity in the inferior frontal sulcus during language tasks involving identification of different pronunciations. The authors suggest that this region is involved in categorisation for both language and non-language activities.
A randomised placebo-controlled trial (using placebo patches) of nicotine patches involving 400 smokers compared those taking nicotine patches before stopping smoking versus taking placebo. Both groups then used the nicotine patches for 10 weeks. At 10 weeks 22% of the first group had abstained from smoking compared to 11% of those taking the placebo before stopping smoking. Adults grow new neurons in the brain – referred to as neurogenesis. The authors of a recently published study found an association between neurogenesis in mice and an improved ability to form more finely detailed spatial maps of the environment suggesting that these new cells are functional which in turn implies that they are integrating with other neurons that form memory. Data from the Dunedin study in New Zealand provided evidence that certain aspects of the family history was useful in stratifying risk of recurrence of specific mental illnesses. Researchers are beginning a study into the use of echolocation in blind people to help them navigate around the environment – this involves producing a clicking sound with the use of the tongue on the palate. The echoes from the clicks should allow determination of objects in the environment and this has already been used. A small fMRI study provided preliminary evidence that improvement in multitasking through training is associated with changes in activity in the posterior prefrontal cortex.
The authors of another Cochrane review concluded that there was insufficient evidence at this point to recommend the combination of Clozapine with another antipsychotic for treatment-resistant schizophrenia. In another Cochrane review which included data from 11 randomised-controlled trials with a cumulative total of 2441 adults identified as heavy drinkers, the authors found benefits for brief interventions with a reduction in alcohol consumption at 1-year follow-up although there weren’t found to be benefits for self-reported alcohol consumption and number of binges. In another Cochrane review there was found to be a significant benefit for the use of TCA’s or SSRI’s in the treatment of depression in primary care in adults (under the age of 65) based on analysis of 14 studies comparing TCA’s or SSRI’s with placebo with a cumulative total of 2283 participants*. In a study looking at prevalence of dementia in later life in low and middle-income countries and involving data from 14, 960 participants there was found to be a significant and inverse relationship between fish consumption and prevalence of dementia in later life. Another study didn’t show a benefit of DHA in mild-to-moderate Alzheimer’s Disease on the ADAS-Cog after 18 months of treatment although another study did show a benefit for older adults with mild memory impairment Evidence for a possible role of fibroblast growth factor (Ffg) in development of the frontal cortex through radial glial cells was provided in one study and there is the suggestion that alterations in the Ffg may have a significant influence on the size of the frontal cortex in humans. In a series of recent studies a large number of acetylation switches(3600) have been found in a similarly large number of proteins (1750) which may be of relevance to a number of diseases and it will be interesting to see the results of subsequent research based on these results. A new ultrasound tool which samples at 125 Hz is being used in attempt to better classify African click languages.
A research team at the University of Vermont have been analysing text strings in blogs to estimate how ‘happy’ people are by looking at sentences with the words ‘I feel..’ in them. They were able to use 10 million sentences (from this site) and amongst their many findings they noted that people increasingly used the word ‘proud’ at the time of President Obama’s election, that Michael Jackson’s death was associated with a big drop in the valence scores (valence scores were calculated by rating each type of emotional word to estimate) and that teenagers were more likely to use the word ’sad’ in the sentence. As the 2012 Olympics approaches a new report has been published which reviews evidence from over 500 papers as well as expert interviews on crowd behaviours – the Understanding Crowd Behaviours Report. A computer simulation of organisms which uses simple variations in behaviour showed that turn-taking developed when organisms with different behaviours ‘locked’ into each other’s behaviour. In essence this suggests that individuals pursuing their own interests can engage in turn-taking behaviour. However this does not negate the possibility that turn-taking can occur for altruistic reasons particularly as decision-making is influenced by many factors in more complex organisms. The authors of a meta-analysis looking at data involving over 8000 subjects concluded that people are more likely to discount information that contradicts the beliefs they already hold and that this tendency is influenced by a number of factors including personality type as well as the context of these beliefs. The authors of a paper looking at studies reported as randomised controlled trials in China identified 2235 studies and contacted the authors/coauthors. They report that less than 7% of the studies referred to as randomised controlled trials involved true randomisation. However this will not be limited to China and is relevant to the wider issue of research methodology.
In a recent poll by the Royal Pharmaceutical Society of 457 people over the age of 65, just under half of respondents reported that they were taking 5 or more medications and 60% thought that they were experiencing adverse side-effects. An american study of 630 drivers aged 55 to 93 found that 28% of the drivers were not aware of the effect of medications on driving. An intriguing in vitro study provided evidence that the antipsychotic pimozide kills several types of cancer cells. There has been a suggestion of closer monitoring of antipsychotic initiation in older adults with diabetes following the results of a longitudinal study of 13,817 older adults (>65 years) who had commenced antipsychotics and finding that compared to a group who had stopped antipsychotic medication 180 days previously there was an elevated prevalence of hyperglycaemia. In a recent poll of 2000 people over the age of 16, there were found to be gaps in knowledge in the respondents in areas of potential importance – for instance 26% of respondents did not think there were approaches to reducing their risk of developing dementia.
A diffuse tensor imaging study (n=20) provided evidence of structural abnormalities in the arcuate fasciculus in people who are tone deaf (half of the subjects were tone deaf). The researchers found that they could not identify the arcuate fasciculus in the right hemisphere. The arcuate fasciculus is a connection between the frontal and temporal lobes. A recent study has demonstrated that ultrasound guided with the aid of Magnetic Resonance Imaging was successfully in ablating tissue in the thalamus in people with neuropathic pain and it will be interesting to follow subsequent research in this area. A mutation in a gene – hDEC2 that occurs in an extended family that require only 6 hours of sleep has been associated with sleep duration using additional indirect evidence. An American cross-sectional study involving 559 women found an association between hopelessness and thickness of the carotid arteries which remained after controlling for depression and other cardiovascular risk factors. The arterial wall thickness is a risk factor for cardiovascular and cerebrovascular disease but it will be interesting to see replication using a prospective study design.
A cross-sectional study (the HUNT study) with 50,843 participants showed a significant association between an increased prevalence of occasional headaches and higher levels of caffeine intake. They also found that lower levels of caffeine consumption were associated with an increased prevalence of chronic headaches. In a small study (n=62) smokers were found to have a significantly reduced blood supply to the tongue and smaller flatter fungiform papillae (taste buds). This is also consistent with other research that shows an impaired sense of smell in smokers (see appendix in this article). The authors of a Finnish study state that they have found evidence that astrocytes mediate the blood vessel changes that are seen in fMRI studies and it will be interesting to see further information on this study as it becomes available. In a small (n=48) observational study of patients with breast and prostate cancer there was found to be a significant correlation between radiotherapy-associated fatigue and markers of cytokine activity and it will be interesting to see further studies in this area. A study in flies demonstrating two pathways – one for long term memory and the other for short-term memory may be of relevance to humans as there is a human homologue of a gene involved in these memories – Rutabaga.
A study with a small sample size provides initial results that suggest that westerners and East Asian people interpret facial expressions differently with the former group focusing on the whole face and the latter group focusing on eyes. However as noted, the sample size here is small and a larger replication study is needed to draw firmer conclusions in this regards. In another study, there was found to be an association between reading emotional words and activation of muscles that are used during expression of those emotions. Further, providing people were able to use the associated muscles they experienced the relevant emotions when reading the emotional words and this influenced their judgements. In a study that compared people who spoke two languages with those speaking just one, researchers found that when reading cognate words, that is words that are similar in both languages, the bilingual subjects took less time to read these words suggesting that learning a second language influenced the way the primary language is processed. In an EEG study, the response to value-laden words was found to occur within milliseconds of presentation if this clashed with the person’s values and such information is of relevance to other areas including neuroimaging. A candidate gene KIAA0319 (on Chromosome 6) was investigated in 322 children with Specific Language Impairment and variations were found to be associated with language ability. In another study, researchers found that a phenomenon known as ‘perceptual rivalry’ occurs with the sense of smell. They presented subjects with two competing smells, one for each nostril and the subjects nted an alternation between the experienced smells. Such competition is noted in other sensory systems such as the visual system. The results of one study indicated equivalent efficacy for both red and blue light in maintaining nighttime alertness. In another study when looking at a clock subjects gave different times when either the clock was brought into their field of vision (in which case the time they gave fell behind the actual time) or if their eyes moved to the clock (in which case the time they gave was ahead of the actual time) and the results were interpreted as meaning that the cortical visual perceptual system anticipates the movement of the eyes.
There has been a presentation on work on lucid dreaming and the relation to dissociation at a recent European Science Foundation workship and there is also a discussion of a threat simulation theory which states that part of the role of dreaming is to recreate the threats that a person has experienced presumably so that they can learn to deal with these threats more effectively (almost like a virtual reality training simulation!). Scientific American have coverage of some studies supporting the hypothesis that long term relationships foster creativity. In the studies they contrasted analytical with creative thinking. The types of relationships considered were tested indirectly by the use of imagination or by presentation of words with subtle meanings related to the paradigm. However it could be argued that the relationship status of the subject would provide more convincing evidence. Steve Peters, psychiatrist and coach for the Olympic Cyclists is appearing on a television program to work with members of the public to improve their fitness. In this article that covers the story, Steve Peters discusses some of the underlying theory he uses (which appears to relate to evolutionary psychology). A 1 Billion dollar Japanese project to create a supercomputer which will amongst it’s many functions will aim to simulate life is currently underway and is covered here. The Natural Health Service is an ambitious project being undertaken in the NHS to plant 1.3 million trees which should reduce the carbon footprint of the NHS. In an intracranial electrophysiological study published in Science, the researchers provided evidence that language processing occurs in Broca’s area and is divided into processes for grammar, meaning and articulation with each process being separated by milliseconds. There is a preliminary report on a new technology which measures electrical signals between the central nervous system and the vestibular apparatus in the ear. The Australian research team state that they are able to characterise responses in a number of central nervous system disorders and they include depression. There is a website which details the technology and which also contains a link to a promotional video. Using Medline, I had been able to find 5 studies including 1 on schizophrenia and 1 on depression, although both had small sample sizes they provided data on the application of the technology. It will be interesting to see further published data with larger sample sizes as this becomes available. In the Proceedings of the National Academy of Sciences there is a paper on the use of a new genome sequencing technology – whole exome sequencing (which focuses on genes coding for proteins rather than the entire genome sequence) in a case which resulted in a rapid diagnosis and it will be interesting to see further developments in this area.
A PET study of 53 people with ADHD compared to 44 healthy controls provided evidence for reduced dopamine receptors in the Nucleus Accumbens. Two large studies ( n=2978 and n=1760) published at PLOS Medicine, looked at how patients make choices regarding medications and amongst the findings, people were best able to understand medication outcome information if this was presented in simple frequencies (e.g. per 100 of the population). Further information on the trials can be found here and here together with a discussion of shared decision making here. An interesting study provided evidence that early stages of the visual perception process were influenced by cue associated emotions and memories. Subjects were presented with faces showing different expressions and the subject’s rating of the emotions in the expressions was correlated with the activation of their own facial muscles when the same faces were re-presented after having been modified to exhibit a neutral expression. Some evidence that reminiscence therapy can improve memory in the elderly is provided from a review of reminiscence therapy studies that was published in Scientific American Mind which also looks at other outcome measures. It will be interesting to see the results of a meta-analysis once further studies are available.
A comparison of longitudinal and retrospective studies provides evidence that people underestimate their experience of mental illnesss retrospectively. An American study of physician-patient interactions in primary care practices in Baltimore found a significant difference in communication-related outcome measures between white and black patients in areas including psychosocial interactions in consultations relating to blood pressure control. The researchers suggest that interventions focusing on doctor-patient communication may influence ‘racial disparities in the care of patients with high blood pressure’ although such research may have benefits in other areas of health care. A new gene association with deafness has been identified. Loxhd1 mutations impair functioning of hair cells and subsequently with hearing. Mutations of this gene were found in some families with deafness (in a genetic database with genetic samples from hundreds of families with deafness). A protein – called the Flower protein – has been recently identified and found to play a role in the processes of endo and exocytosis whereby neurotransmitters are packaged into vesicles, released from the neuron and the membrane resorbed. Aggregates of the protein form channels which allow the entry of calcium into the cell and the research team suggest that this protein could be responsible for the close and necessary coupling of endocytosis and exocytosis.
The researchers in a study in Neuron found an association between modifications of cortical theta oscillations and the perception of intact sounds when presented with fragmentary sounds. Thus the implication is that there is an EEG correlate of auditory illusions. A recent study looking at falls in older adults found associations with a number of medications. The researchers in another study looking at falls in the elderly (the MOBILIZE study, n=729) found that those with chronic pain were significantly more likely to fall than their counterparts without. An American study showed that just under half of the 3 to 6 year olds in the study were concerned about becoming obese and one-third wanted to change an aspect of their appearance. Another American study (due to be published next year and with n=184) contrasted brief motivational interviewing with a control intervention (warning about the hazards of drinking and driving) in drink-driving recidivists was associated with a 30% reduction in repeat offences. Another study offers preliminary insights into the potential role of the delta waves generated in the hippocampus and the authors hypothesise on the basis of their results that the frequency of the delta waves code information about the type of processing that should take place in different regions – processing about the past or present.
An american study is looking at whether PTSD can be predicted by incorporating a number of biological markers. The Lean Healthcare Academy recently had an awards ceremony and a hospital which implemented the Productive Ward was the recipient of an award. The Productive Ward and related Productive Series involve a systematic process to enable improvements in outcome measures such as efficiency (see review here). It is interesting to see how American and Japanese culture and technology is being used to improve care for patients in the NHS in an ever more connected world. The Productive Ward series is covered at the National Institute for Technology here. The series also includes approaches to improve outcomes in community care as well as other types of service. Mind Hacks has coverage of a number of studies including one in which sounds presented during sleep were associated with improved learning on spatial tasks.
The National Institute of Clinical Excellence has released guidance on mental wellbeing at work. The document has a wide audience including members of the public (where applicable in the UK) and complements previous NICE guidance in the workplace. The quick reference guide contains 5 recommendations relating to strategic/coordinated approaches to mental wellbeing, assessment of opportunities for wellbeing of employees, flexible working, the role of line managers and supporting micro, small and medium-sized businesses. This has been widely reported with a number of articles looking at how these recommendations might impact on health services themselves (see here, here and here). This comes at the same time as a report by the Chartered Institute of Personnel and Development (CIPD) which produced findings from a survey of 2000 employees which included results relating to mental health (covered here). The researchers in an american study covered here found that of 472 million prescriptions for psychotropic medications prescribed between August 2006 and July 2007, only 1/4 were prescribed by psychiatrists. Virtualised desktops save time in booting up the computer and in this article a proprietary system using virtualised desktops was suggested to save clinicians 30 minutes on average each day
A study of babbling in babies (covered here) found evidence that after only an hour’s exposure to a new language, the baby’s babbling with the speaker of that new language differed from that with speakers of the native language. An 11.7 T MRI scanner is being developed in France through a pan-European partnership and is due to begin operating in 2012. A recent study involved 205 Norwegian couples and used ‘client feedback’ therapy during problematic episodes in their relationship. At 6-months after the last session, the researchers reported a 50% reduction in divorce or separation rates compared to those who did not receive this intervention. The approach is described as patient focused research (the Research Advocacy Network has more information on this). There is preliminary evidence that inflammation in the hippocampus may be associated with schizophrenia although it will be useful to see the results of further studies in this area. In a study (n=109) of people with depression and controls there was found to be an association between depression and overestimated retrospective recall of somatic symptoms and this is just one of many ways in which depression and physical illness may have complex interactions. There was a recent study which used a large number of outcome measures which investigated collectivist versus individualistic cultures and the authors suggest that the former are associated with a lower genetic predisposition to depression. However it is important to note that there are cultural differences in the use of diagnostic classifications (e.g. see this review). Technology review have a collection of images about representing 100 years of visualising the brain. A comedian has been invited to contribute a humorous perspective to a production on mental health by a primary care trust. There is a clip of the performance in the article and the argument is that the comedy can help to overcome stigma through education. You can see the responses of members of the audience in the clip. If this were so, it would have many implications. Another paper on genetic material – heterochromatin may in the future help to answer the question of whether the offspring would be sterile.
DSM-V and ICD-11
In the BJPsych there is an interesting article by Professor Michael First who writes about the potential for harmonisation of DSM-V and ICD-11 which is a widely discussed topic (First, 2009). There are a number of points of interest in the article and he notes that there are investigators involved with revisions of both systems which should help to contribute to attempts to harmonise both systems. The discussions around these systems will no doubt increase.
There was discussion recently of the diagnosis of Asperger syndrome being dropped from the next edition of the DSM and this will mean an expansion of the autism diagnostic category. This was originally discussed in a New York Times article (which requires (free) registration). The article features an interview with Dr Catherine Lord, who is one of 13 members of the working group on autism and neurodevelopmental disorders. The group are considering a number of amendments to the autism diagnosis including the addition of comorbidity that have been associated with the condition including disorders of attention and anxiety. However the suggestion regarding Asperger syndrome has not yet been ratified by the group. There have been a number of responses in the media. This article contains interviews with a doctor who runs a clinic, a parent of a child with Asperger’s syndrome and the president of a non-profit organisation for raising awareness of the condition. There is some information on the DSM-V process here.
DSM-V is due to appear in 2012. A twitter campaign has been started to petition for the inclusion of Depressive Personality Disorder in DSM-V. Professor Simon Baron-Cohen has argued against the removal of the Asperger Syndrome label in this New York Times article. Dr Anestis offers his views on this article and Baron-Cohen responds in this blog post.
A paper which is causing a lot of heated discussion in the blogosphere is titled ‘Voodoo correlations in social neuroscience‘ by Vul and colleagues. This was initially reported on at Mind Hacks (see here). Neurocritic has been reporting in depth on this (see December 2008 (31.12.08 ) and January 2009 (15.1.09) posts). There are various points being made such as the reporting that has occurred in the media before the authors have been able to respond in print, the effect of reporting on perceptions of social neuroscience research and the potential benefits of the current dialogue.
On the 10th anniversary of Nature Neuroscience, there is a post outlining the most cited studies the most popular of which was a study looking at the development of Parkinson’s Disease in people chronically exposed to pesticides. Dr Shock links to an educational video about the redesign of the PubMed interface which is useful for those undertaking literature reviews, database searches and related activities. Sandy Gautam has started a new blog – My 2 Brains and in this post he reflects on twitter including a look at how it relates to the expression of self. MindHacks has his weekly round up here. There is an article here about web-based healthcare. The Journal Cell has an article on twitter and at least one of the scientists quoted in the article found that it was useful in keeping up to date with developments in their field. The FDA has convened the social media hearings to examine the issue of regulation of pharmaceutical companies use of social media and this has been widely discussed in the mainstream media, the blogosphere and the twittersphere. An article here has lots of discussion in the comments section.
This BBC article looks at Google Wave and includes a interview with the founders and some examples of use. Google wave is a collaborative tool that is described as facilitating the linking of ideas and data, allowing for instance data to be inserted relatively easily by multiple authors into a collaborative document. There is further coverage of Google Wave applications in this article which contains an embedded video and lists uses including research where Google Wave has provided benefits. The ICS healthcare blog has an article on how the doctor-patient relationship might be changing due to the influence of factors such as health 2.0. Ted Eytan in his blog has coverage of a study published in May that involved a focus group of patients who use the internet. The findings included an expressed interest by the people in the study to have access to their medical records. ‘360 digital influence’ discuss trends in the use of social media by doctors here including a look at research in this area. John Grohol has an article at PsychCentral on how ‘first impressions count’ online and argues that these impressions are formed through inspection of photographs and he also reports on a study looking at Facebook use which is due for publication next year. There is a presentation available here on how web 2.0 might affect education. The Gov 2.0 conference is due to take place online on December 10th 2009. Biomedcentral has an open-access article on a ‘database of everything’. A German petition is currently underway requesting that all publicly funded studies should be made available through open-access articles. The ZZoot blog has coverage of a recent workshop on the future of the semantic web for scientific communication. In this article there is a look at an organisation which matches researchers with research participants.
There is further discussion of the DSM-V Asperger syndrome diagnosis on the left-brain, right-brain blog and at the time of writing there are 87 comments, testimony to the interest this discussion is creating. Dr Grohol also covers this over at Psychcentral. At the ISCI healthcare blog there is an article looking at some of the ways in which twitter is being used in healthcare. MindHacks has another news roundup in ‘Spike Activity‘ and included is a link to an interview with Terry Pratchett about Alzheimer’s Disease. The ‘Heal My PTSD‘ blog contains a round-up of Post-Traumatic Stress Disorder (PTSD) news including the use of a virtual reality environment for re-experiencing trauma as part of a therapeutic intervention. This BBC article looks at some of the ways web 2.0 technology is being used by the research community. Patients in the USA are beginning to carry their healthcare information around with them in iPhone apps as reported in this article. The Science in the Open blog has an article looking at how an open collobarative framework might change science (Science 2.0) with the possibility of the science being separated into data acquisition, data analysis and dissemination of results. An article here looks at recent research which counters the argument that use of the internet has casued people to become more isolated. They cite research which suggests that people are not more isolated than in 1985 and elsewhere that people who use the web regularly are more likely to participate in social activities such as meeting up with friends . See here for more information.
The Google Wave tool which has been recently rolled out enables live collaboration using a number of tools and in this article Leah Betancourt discusses some of the ways this is being used in the creation, dissemination and discussion of news. Conventional methods for disseminating scientific/clinical information including conferences, journals and books are now in the process of being transformed by such tools. Another development which has the potential to have a profound impact on society, Government 2.0 was discussed at a recent conference. The idea here is that citizens can both engage with and contribute to the decision-making process of government. As an example this may impact on the way in which different segments of society are represented and this in turn could impact on health and illness on a number of levels. The American Association for the Advancement of Science has set up an expert lab to help government engage with citizens using technology and enabling them to tap into ‘crowd expertise’. There is a video on the expert lab here. In an american survey by Manhattan Research, 39% of doctors stated that they had communicated with patients online although the insurance-based nature of the healthcare system may influence such relationships. An article here looks at how doctors are using technologies such as twitter and the iPhone in their practice. Meanwhile the Danish Government is intending to go paperless by 2010. The ‘Heal My PTSD’ blog has a news round-up which includes the use of telemedicine for PTSD. Mind Hacks has an episode of Spike Activity where he reviews the news including a link to a study showing an association between creativity and horizontal eye movements, adding to previous research suggesting an association with recall of information. A study published in Science (n-192) and using a public goods game paradigm (used in the study of group behaviour) provided evidence that using a reward strategy for ‘good behaviour’ produced better outcome (e.g. contributions to the group) than with the use of punishment for ‘bad behaviour’.
In a small study, participants were observed using search engines. The researchers concluded that search strategies were influenced by the learning styles of the participants and that participants often used search engines to confirm then own recall of a subject. A recent MyPublicServices event was held to discuss ways in which social media might impact on public services. It was suggested at the conference and reported in this article, that social media may impact on public health service delivery as it has done in many other sectors and that a constructive approach to using social media in th9s area could be adopted. One research study into viral marketing campaigns focused on the characteristics of e-mavens – people who spend a lot of time online**. E-maven’s characteristics were identified and those that were more likely to forward viral material onto others scored more highly on measures of individualism and altruism. An emergency mobile text message system for people unable to use their voices in calls is being trialled by a number of UK telecommunication companies. A study looking at twitter provided evidence that 20% of twitters involve exchanging information about ‘products’. Epi Collect Software on mobile devices has been piloted which enables ‘citizen scientists’ to gather data for science projects incorporating their location within the data. There is evidence from a small Japanese study (n=48) that male teenage young offenders are more likely to misinterpret disgust as anger than male teenage non-offenders.
An application – healthii – has been developed with the intention of improving the well-being of people engaged in social networking online. A recent trial on Twitter at the end of August and the findings should be reported in the near future. A Twestival Local (a local festival on twitter) is taking place (see the site here) to raise money for charity. There are two types of festival – one is global and the other involves individual cities which are identified on the map here. This shows one of the many extraordinairy ways in which Twitter is impacting on society globally. Over at Science Life there is coverage of the Neuroscience conference in Chicago which amongst other items reports on a talk by Erik Kandel, the genetics of anxiety and neuroscience in social media. October 19-23rd was Open Access week and over at Beta Science, Morgan Langille writes about the use of an open-access website BioTorrents for sharing data and other resources. Over at Medical News Today there is a look at an association between gamma synuclein and depression. Software Advice has an article on iPhone applications for doctors and medical students.
The NHS has been criticised in a developing argument about the future of American Healthcare and Gordon Brown has joined in the defence of the NHS using twitter! There has also been some recent research on Twitter that shows that just over 40% of the postings contain information about the minute-to-minute actions of the twitterers although just under 40% of postings were conversational. A Stanford study published in the Proceedings of the National Academy of Sciences looked at 100 students, examining how they responded to the data they were presented with. The students were divided into those that those frequently ‘media multitask’ (which means that they take in information from multiple media sources which is contrasted with focusing on a single task at any given time) with those who did not. The group found that the multitaskers performed worse than the comparison group on a number of measures including distractability. The study has been widely reported (e.g. here, here, here and here). In the Blogosphere, the study has been covered over at MindHacks and Not Exactly Rocket Science and the key point is that this study is demonstrating association rather than causality. So for instance, the heavy multitaskers may use this approach because they have a different cognitive profile. In a Swedish survey of 4500 people it was found that there were more older people (aged 65-79) online and that for all ages, 8% of online activity was spent in the ‘blogosphere’. A recent study involved 1224 bloggers and found that the main principles which bloggers valued were ‘truth, accountability, minimising harm and attribution’. Depending on the purpose of the blog, the priority of these values differed.
The Neuroscience Information Framework Version 2.0 is now online. The NIF is described as
‘A dynamic inventory of web-based neuroscience resources: data, materials, and tools accessible via any computer connected to the internet‘
The NIF is also described as a National Institute of Health Blueprint for Neuroscience Research initiative (see also this review of a paper on the Neuroscience Information Framework). The NIF Tools include a registry of electronic catalogues of neuroscience resources, a ‘deep web’ resource – the NIF Data Federation, the NIF Web Index – essentially a search tool for neuroscience information on the internet and the NIF vocabulary which includes Neurolex. Neurolex is a neuroscience lexicon which at the time of writing contains 7972 terms. Such a lexicon has implications not just for the ability to find relevant information on the internet but also has potential for facilitating neuroscience dialogue.
It is a privilege for the TAWOP blog to have been included in a list of 100 blogs for psychology students and there are many interesting blogs included in this list.
Evolutionary Psychiatry
Recent evidence suggests that the Sahara may have experienced wet periods roughly 120,000 years ago and 50,000 years ago and that this may have facilitated the migration of early humans across the Sahara. There is an article at Live Science on the decreasing size of the human brain over the last 10,000 years which asks the intriguing question ‘is our evolution accelerating?’. In a fascinating anthropological study of the fairy tales Little Red Riding Hood shows that this fairy tale probably has a very ancient origin. There were subtle differences across the world – for instance in China the wolf is replaced with a tiger. The most closely related versions to the modern European were those from Nigeria and Iran. There are many forms of analysis of fairy tales including psychoanalysis (see here, here and here for instance.
There were also a few Neanderthal studies recently. These are of increasing importance because the Neadnethal genome is being sequenced and the differences between the human and Neanderthal genome may give clues to the genes that are involved in human intelligence. The first is that a study of the genome obtained from Neanderthal specimens from Croatia reveal that a specific gene – Microcephalin 1 suggests that they did not interbreed with Homo Sapiens. The group however are examining possible speech capabilities given that they share the FOX-1 gene that is one of many genes associated with speech. . The other piece of research looks at climate changes in the Iberian Peninsula (using marine core samples which allow determination of sea level) where it was found that there was a drop in sea level coinciding with the presumed extinction date of Neanderthals in that area (in the absence of evidence to the contrary). The hypothesis is that Neanderthals in that area would have been exposed to a drought which led to their extinction rather than competition with Homo Sapiens who did not arrive in that region until much later. There is a recent statement from a geneticist Professor Paabo that Neanderthals and humans interbred according to analysis of the Neanderthal genome (see also here). It will be useful to see further evidence when it is published. However the remaining question is whether or not the Neanderthals contributed to the modern human gene pool which is a separate although related question which may be answered with the completion of the sequencing of the Neanderthal genome. Evidence from a Spanish 48,000 year old Neanderthal specimen shows the presence of a gene coding for bitter taste meaning the detection of bitter tastes occurred before the divergence of Neanderthals and humans.
Recent evidence supports an emerging theory of friendships – the Alliance Hypothesis. A previous theory states that people have friendships in which they count up the number of reciprocal gifts or tokens although there is a lot of data that doesn’t support this model. However the authors of the Alliance Hypothesis posit that people have friendships for times of conflict and that they prefer friends who are interested in their needs. A recent study suggests that people rank their friends similarly to how their friends rank them. The authors of a model propose that marked changes in culture may more influenced by population density than the characteristics of the brain. A 300-million year old brain has been discovered in a distant relative of the shark. An fMRI study in monkeys and humans provided evidence of activation of the inferior Parietal lobe in humans alone when watching tool-using activities. There were a number of other areas that were activated in both humans and monkeys when undertaking this task. Researchers have provided indirect evidence that Macaque monkeys experience the ‘Uncanny Valley‘ effect. This effect describes the tendency for people, or monkeys in this case, to become uncomfortable if computer simulations of members of their species are too realistic. The finding in monkeys suggests an evolutionary basis for this effect. It will be interesting to see if this has implications for social bonding. An anthropological study looked at old world monkeys and found that increasing neocortical size was associated with the ability to form large social networks. There is an estimate from one study that each person has roughly 100 new mutations in their genome based on an analysis of the difference in genes in two chinese men who shared an ancestor at the beginning of the nineteenth century. Research showing that pigeons and baboons are capable of same-difference discriminations.
The new buzz word in this area is ‘primate archaeology’ which is an attempt to integrate a number of areas including primatology, anthropology and psychology. This article summarises this new ‘movement’ and looks at some very interesting research into the use of stone tools by chimpanzees in what is being described as a parallel with the advent of the stone age in humans. Evidence has been found that a species of New World Monkey – the Cotton Topped Tamarin are able to distinguish between ‘affiliate’ and ‘fear’ music produced by other monkeys. Such studies are useful for debates in Evolutionary Psychology. Dr Shock has a link to a video showing that squirrels work together to recall where food is located in the environment. The combination of social cooperation and memory abilities displayed here may be important in understanding similar abilities in primates including humans. Researchers found in one study that Capuchin monkeys spent more time near researchers if they mimicked the monkeys which was interpreted as meaning that mimicry is important for social bonding in these monkeys. If such findings are replicated and this mechanism has been conserved through primate evolution it may have implications for social interactions in humans. Another study looked at chimpanzees and finding that they forage for fruits over wide distances and have good recall of trees that are bearing fruit in season. This ability to group objects would be helpful in scanning large areas for food and needing to economically remember where food of interest is located.
A female Gibbon has been observed to slam a metal door in way which accentuated her territorial song suggesting a distant beginning for the use of percussion. A recent study provided evidence that Rhesus monkeys and humans share a similar mechanism for recognising faces by using a paradigm which involved the ‘Thatcher Effect’. This involves inverting facial features, the eyes and mouth and interferes with the task of facial recognition in both species. There is also evidence that neighbouring groups of Chimpanzees approach the same problem in different ways which the researchers have interpreted as cultural differences. Such interpretations may have implications for developing models of human culture. The FOX-P2 gene product in chimpanzees was found to behave differently to the gene product in humans in a recent study which might contribute to an explanation for the absence of spoken language in chimpanzees. Also an ancient brainfrom approximately 6000 years ago has been discovered in a cave (it was preserved due to the dry conditions) in Armenia with evidence of intact surface vessels. Such a find is potentially very interesting as even in the space of tens of thousands of years there is evidence of evolutionary changes in the brain. A team looking into the extinction of Neanderthals have found the remains of late ice age animals in a cave in Torquay and the remains include what could be a 25,000 year old Hyena. New radiocarbon dating, dates human remains in Gough’s Cave, Somerset to 14,700 years ago. Three 35,000 year-old bone and ivory flutes have been found in Germany. A 4000 year old tomb has been found in Forteviot, Scotland causing a significant reevaluation of not only local history but also significant events in Neolithic culture.
2010
2010 was an exciting year in many ways. A draft version of DSM-V was published – the American diagnostic manual for psychiatric illnesses. There was lots of controversy and further discussion is still underway. There were new findings on an important region of the brain referred to as the default mode network which may be susceptible to the changes found in Alzheimer’s Disease. The involvement of neuroanatomical structures in cognitive impairment was further investigated and initial results suggest the subiculum is particularly relevant in Alzheimer’s Disease in comparison to CA1-3 while the cerebellum also appears to be playing a role in mild cognitive impairment. Gene therapy is being trialled for Alzheimer’s Disease in one study but in the CONNECT study, Dimebon did not meet its early promise. A new classification approach to frontotemporal dementia has been developed while three new variants of primary progressive aphasia have been identified. The benefits of physical activity in people with Alzheimer’s Disease are further identified in another study. In schizophrenia research, a big finding was the chromosome 22 gene association with hippocampus-prefrontal cortex disconnection. Comparisons between Schizophrenia and Alzheimer’s Disease have been made and there are findings that exercise can increase hippocampal volume in people with schizophrenia while there have been initially promising results for the use of acetylcholinesterase inhibitors in schizophrenia also. The use of Tetris to interfere with traumatic memories and prevent the onset of post-traumatic stress disorder was another interesting approach. An interesting evolutionary hypothesis was that cooking influenced the development of the hominid brain because of the impact it makes on energy consumption. For me the most groundbreaking study of the year was Paabo’s study on the Neanderthal genome. Analysing the DNA from 50,000 year old bones is no easy matter but Paabo’s team sequenced most of the genome and found that they contributed to the human gene pool. There is still a lot more work to be done on the genome but no doubt this will lead to further insights into various aspects of our biology in a quite profound manner.
Dementia
The National Institute of Clinical Excellence have reappraised their guidance on the use of drugs for Alzheimer’s Disease (see here) with the result that the consultation document states that the acetylcholinesterase inhibitors that are already in use can be used at an early stage of the disease and the drug Memantine can be used at the more advanced stages of the illness rather than being restricted to the research setting. The Alzheimer’s Society have produced a more detailed explanation on their website here. The final document is scheduled to be published in March 2011. A small study (n=245) finding clinically and statistically significant increases in both apathy and depression in Alzheimers’ Disease compared to Mild Cognitive Impairment. A small study finding involvement of the anterior corpus callosum in Amnestic Mild Cognitive Impairment extending to the posterior corpus callosum in Alzheimer’s Disease.
The other was a double-blind study published in PLOS-One. The NHS Choices detailed coverage is here. Essentially they took a relatively small group of people with mild cognitive impairment and randomised them to either a combination of high dose Vitamin B12, B6 and folic acid or else placebo. The subjects underwent an MRI scan of the head on entry to the study and two years later. They found that there was a 30% reduction in the rate of cerebral atrophy in the group on the high dose vitamin therapy. There were a few limitations however. Firstly there is the sample size – they have 168 people included in the final analysis. The second point is that the actual shrinkage is quite small – 0.76% versus 1.08% in the placebo group and over a relatively short time period (2 years) it is difficult to determine the significance of this. For instance, one of the most significant predictors of conversion from one form of MCI – amnestic MCI to Alzheimer’s Disease is the volume of the hippocampus rather than the cerebral volume. Another point is that we don’t know which people in the group were converting from MCI to dementia and the study wasn’t designed to detect changes in cognition between the groups. Still the result is interesting and they add some supportive evidence for the effect being mediated by homocysteine levels although as with the above study replication is needed with a slightly different design to address the above issues.
There was a Small study using Diffuse Tensor Imaging to focus on white matter changes. The authors write that
‘Present findings suggest that most DTI-derived changes in AD and a-MCI are largely secondary to gray matter atrophy‘
There were some white matter changes noted however. One small study showed evidence of hypoperfusion in the frontal lobes and hyperperfusion in the parietal lobe in Frontotemporal Lobar Degeneration and a reversal of these findings in people with Alzheimer’s Disease. The authors of one paper have produced a mathematic model of Alzheimer’s Disease progression using ADAS-Cog scores as the dependent variable and basing their results on data from the Alzheimer’s Disease Neuroimaging Initiative. In a moderately sized prospective study with an albeit short follow-up period of 1.5 years, people with incident Alzheimer’s Disease who engaged in physical activity experienced significantly lower mortality than those who were inactive even after controlling for confounders. There wasn’t an association with rate of cognitive decline although there is other data which supports such a relationship. Anosognosia for amnesia was found in people with Alzheimer’s Disease but not mild cognitive impairment in this small study.
Two interesting papers have been published by the Proceedings of the National Academy of Sciences (see here and here). Taken together they provide evidence which suggests that a specific region in the brain known as the default mode network is more likely to develop Alzheimer’s Disease associated pathology due to peculiarities in the way energy is produced in this region. There’s been a good write-up at the Alzheimer’s Forum on this (see here). The researchers are telling an interesting story with many twists and turns.
When we need energy to do various activities we use one of two mechanisms to get that energy. Glycolysis is the process by which glucose is broken down to produce energy. This can take place through anaerobic or aerobic means. When we suddenly sprint over a short distance we need to get energy very quickly if there isn’t much oxygen available. The term used for this type of energy release is anaerobic glycolysis. The schematic diagram below illustrates this process in which glucose is broken down through several steps releasing the energy-producing molecule ATP as well as lactic acid which leads to muscle fatigue.
In the second case, when we are jogging over a long distance, there is more time to get oxygen to the muscles and we are able to make use of another process known as aerobic glycolysis.
The process of glycolysis is linked to another important energy producing pathway known as oxidative phosphorylation. In this reaction, electrons are transferred between molecules involved in the pathway and the end result is that a large number of energy producing ATP molecules are created. This pathway is very good at creating energy.
These two processes – glycolysis and oxidative phosphorylation have been well described and are found in introductory texts in biology and physiology. The researchers in these studies were interested in aerobic glycolysis – that is the process by which glucose is broken down to produce energy in the presence of oxygen. The energy produced by oxidative phosphorylation is so great in comparison with that produced by glycolysis alone that it has often been overlooked when looking at energy use by the brain. This is just one of the ways in which the researchers have been quite innovative in these studies.
If we turn to where energy is needed in the body, we find that the brain uses approximately 20% of the body’s energy consumption. Therefore the issue of how the brain uses energy is critically important. Needless to say the methods by which the brain consumes energy are extremely complex and may involve a sophisticated interplay between the brain’s support cells – the glial cells and the neurons. In order to investigate aerobic glycolysis, the researchers used measures of glucose consumption and oxygen consumption in the brain. By calculating the expected oxygen consumption for the given glucose consumption, the researchers were able to estimate the extent of aerobic glycolysis in different parts of the brain. It was here that there is another interesting twist in the story. The researchers found that a part of the brain known as the default mode network appeared to account for more of this type of activity than other parts of the brain. The default mode network involves several regions of the brain that are active during ‘wakeful rest’. The network is characterised by a synchronous firing activity of these different regions at roughly once every ten seconds. The network is thought to be associated with introspective activities in contrast with the brain’s responses to events in the environment. Below is a diagram illustrating the default mode network at different stages of development.
There is some evidence to suggest that the plaques that build up in Alzheimer’s Disease are more likely to be found in the regions in this network. So next, the researchers turned their attention to a component of the plaques found in Alzheimer’s Disease – ABeta peptide. Using a radiolabelled isotope which shows up this peptide in the brain, the researchers used PET scans to examine both people with Alzheimer’s Disease and people with high levels of ABeta peptide in the brain but who were cognitive normal. They found that in both groups, the ABeta peptide was more likely to be found in the regions in the default mode network. Furthermore it was more likely in those people with Alzheimer’s Disease than in those without.
While it’s tempting to draw some general conclusions about what this might mean in terms of introspection and response to external events, it is far too early to do so. Indeed it is far too early to even draw conclusions about energy metabolism and Alzheimer’s Disease. The total sample size in both studies was 58 people and so really what these studies are doing is telling us about what areas in the brain are likely to be affected in Alzheimer’s Disease, which mechanisms might be making them vulnerable and how all of this might tie in with the way the brain creates and uses energy. However there is a need for further studies to reproduce these results with a larger group of people and also to test these theories in different ways to see if they stand up to close scrutiny. If these theories do stand up to close scrutiny then they will give us exciting new insights into some of the mechanisms producing Alzheimer’s Disease and offer the possibility of novel therapies based on this understanding. So this will certainly be an interesting area to follow.
There is a write-up of a study published in the journal Neuron in which researchers found that the Alzheimer’s Disease associated tau accumulating in the dendrite interfered with synapse relay between neurons even before evidence of degeneration of the neurons. In Alzheimer’s Disease research, the Gamma Secretase inhibitors have been problematic as they inhibit not only the desired enzyme but also the functions of the NOTCH protein which has many important biological functions. At the Alzheimer’s Forum, the authors write about recent research published in Nature in which the researchers developed a compound that inhibits Gamma Secretase effectively but not the NOTCH protein functions and it will be interesting to follow subsequent research in this area.
In America, there is a region known as the ‘stroke belt’. As the name suggests, this is a region with an increased prevalence of strokes relative to other areas. The researchers in one study found evidence that people in this area were consuming higher levels of fried fish than in other areas and suggest that the saturated fats would counteract the anticipated beneficial effects of unsaturated fats found in fish. In a prospective cohort study of 417 people with intracerebral haemmorhage a small subset underwent post-mortem analysis. 23% of people with lobar intracerebral haemmorhage had pre-existing dementia with 5 post-mortem analyses revealing a combination of Alzheimer’s Disease and cerebral amyloid angiopathy. In the deep intracerebral haemmorhage group the 5 sampled subjects had small vessel disease without Alzheimer’s Disease. The Informant Questionnaire on Cognitive Decline in the Elderly was used to assess cognition in this study.
One study looked at post-mortem brains in a sample with Alzheimer’s Disease (AD) or Lewy Body Dementia. The researchers were interested to learn about Lewy Body Dementia in different age groups. The samples were divided into 70-79, 80-89 and 90+. The researchers found that the frequency of LBD was lower in the two older groups but the cognitive impairment was similar for all three groups. The severity of neuropathology and clinical manifestations correlated only in the youngest group although synaptophysin severity correlated with the clinical severity in the oldest group. Researchers have found evidence of a protective allele – TMEM106B allele against the development of frontotemporal dementia in those with progranulin gene mutations (another risk factor for frontotemporal dementia).
NHS Choices have reviewed a recent study investigating the use of self-reported cognitive activity in older adults. The study had a longitudinal design and a reasonable sample size (n=1157). The study showed a positive association between cognitive activity and delayed onset of dementia but was also associated with a more rapid rate of cognitive decline after onset of dementia. There were various interpretations of these results but the authors of the review point out that the results may have been influenced by a number of confounding factors and that replication with adjustment for confounders is needed before firmer conclusions can be drawn. An open access systematic review of non-pharmacological interventions in dementia has been published here – the researchers find a good evidence base to support various interventions but depending on the outcome measures used. There is a write-up of the Experimental drug pc73 and effects on preservation of memory function and it will be interesting to see further research in this area. Findings from a 2-year prospective multicentre study are outlined in this article.
There have been a number of interesting developments in therapeutics. A neurosurgical study is underway which involve gene therapy for Alzheimer’s Disease. A nerve growth factor will be delivered to cells in the Basal Nucleus of Meynert using an adenovirus vector. A drug 7,8-dihydroxyflavone has been identified which acts on the trk receptors just as Brain Derived Nerve Growth factor does and may therefore stimulate neurogenesis and it will be interesting to follow further studies in this area. A molecule Nmnat2 has been identified which is necessary for survival of neurons in vitro. Increasing levels of this molecule was associated with protection of neurons against insult. Lansoprazole, more commonly used in the treatment of gastro-oesophageal reflux and gastric ulcers has found a new use this time for research in Alzheimer’s Disease. Lansoprazole has been found to bind to a pathological form of tau-protein which is found in the plaques associated with Alzheimer’s Disease and it’s use as a radioligand in PET studies is now being investigated.
Over at the Alzheimer’s Forum there is coverage on some recent genetics papers showing the possible involvement of a number of Progranulin mutations in the pathogenesis of Frontotemporal Dementia. There is coverage here also. Scientific American has an article on neurogastroenterology – the study of the enteric nervous system and has some intriguing comments on how a ‘mental illness’ could affect this part of the nervous system which uses serotonin amongst other neurotransmitters. They suggest that there might be insights into irritable bowel syndrome and it will be interesting to see how this develops. The authors of a small study (n=54) found evidence of reduced response inhibition in subjects with Type 2 Diabetes. A recent study that has attracted media interest is a murine study suggesting that looking at nerve cell death in the retina can be used to predict Alzheimer’s Disease. This is covered in more detail at the NHS Choices site where it is noted that human trials are awaited before such conclusions can be drawn. Several studies providing evidence of an association between amyloid protein-induced damage to the microtubule system in human and murine cells and Down’s Syndrome, Alzheimer’s Disease and atherosclerosis. It will be interesting to see further supporting in-vivo studies.
Brain-Derived Neurotrophic Factor has been suggested as a possible therapeutic intervention in dementia. The authors of a new study reported on here found that slow versus rapid application of BDNF to cell cultures had different effects and this is discussed further in the report. Alz Forum report on a study providing further evidence of an association between Brain Derived Neurotropic Factor and hippocampal volume. A common allele of the FTO obesity gene is associated with reduced brain volume in the health elderly. Donepezil in a 24-week placebo-controlled trial in Vascular Dementia with ADAS-cog primary outcome and differential effects according to hippocampal volume (n=974). There was found to be a negative finding of an association between metabolic syndrome and risk of dementia (n=749). At the Alzforum, this post links to a report on a recent virtual conference on Mild Cognitive Impairment with a focus on biomarkers. There is further fMRI evidence (n=36) to support discrimination between behavioural variant Frontotemporal Dementia and Alzheimer’s Disease using functional networks – the Default Mode Network and Salience Network. An autopsy study n=168) comparing patients with Lewy Body Dementia (LBD), Parkinson’s Disease (PD) and a control group and the researchers found a significant reduction in comorbid
‘severe cerebrovascular disease or history of stroke‘
in the LBD group. There was a negative finding for benefit of statins on cognitive function (n=548) in older adults in one study. A new gene association with late-onset Alzheimer’s Disease has been found using a GWAS (genome wide association study). The gene is MTHFD1L and is located on chromosome 6. A small phase II trial (n=24) of intravenous Gamma Globulin has shown evidence of reduced ventricular enlargement and brain atrophy in people with Alzheimer’s Disease compared to the control group. It will be interesting to see the results of the Phase III study when completed. The American Academy of Neurology have updated their guidelines on driving advice for people with dementia. Loss of muscle mass was associated with Alzheimer’s Disease in one study and a suggested explanation was an association with reduced activity. In another study there was found to be a strong association between ABeta oligomers in the CSF and performance on memory tasks in people with Alzheimer’s Disease. A prospective study (n=2148) looked at risk of Alzheimer’s Disease according to dietary patterns and identified one diet associated with a clinically and statistically significant reduced risk. See here for further details. Dimebon has been a candidate treatment for Alzheimer’s Disease after an initially promising trial reported in the Lancet (see here for further details) and is used in Russia as an antihistamine. However the results of two Phase 3 trials have been recently reported. In the CONNECT study – a double-blind, placebo-controlled trial (n=558), Dimebon did not meet statistically significant improvements on the primary or secondary points relative to placebo. There is still another trial in Huntington’s Disease underway and the company have further information on Dimebon here.
Researcher Kausak Si teamed up with Eric Kandel to investigate the role of a protein called CPEB in slugs. The CPEB is located in neuronal synapses. When the researchers targetted antibodies to CPEB they interfered with the ability to form new memories. They found that CPEB was similar to prions found in Yeast and have speculated that self-replication might play a role in memory formation (although they didn’t have evidence from this study for that particular hypothesis). Prions have been identified in a number of pathological conditions including Creutzfeld-Jacob disease. rather than in health. There is a report here on two studies that looked at processing of emotions in Parkinson’s Disease. One was a meta-analysis that showed a reduction in outcomes of emotional processing across a number of tasks while the other looked at the effects of a subthalamic stimulating device on emotional processing. An Italian group provide evidence that Frontotemporal Dementia can be usefully divided into two broad groupings based on performance on neuropsychological tests (Borroni et al, 2010). A small study (n=12) showed preliminary evidence of a benefit for methylphenidate for apathy in Alzheimer’s Disease and it will be interesting to see the results of further research (Padala et al, 2010). In a large open-label trial (n=4460) response of six symptoms to Rivastigmine in people with Alzheimer’s Disease was assessed using the CGI-C – ‘attention, apathy, anxiety, agitation, irritability and sleep disturbance’ (Gauthier et al, 2010). The authors reported a large proportion of subjects improving in these symptom categories (compared to worsening of symptoms) but the randomised control trial would avoid some of the biases noted by the authors.
Over at AlzForum, there is a report on an interesting finding that histone methylation may be associated with learning. There is also an Alzforum report on research suggesting that impaired neurogenesis could lead to an impairment in cognition preceding some of the more well-recognised pathological changes seen in Alzheimer’s Disease. By using a combination of structural imaging and psychometry, the researchers of one study provided support for a dual-process theory of familiarity and recognition (i.e that these are distinct constructs) (Wolk et al, 2010). The researchers compared controls, people with Alzheimer’s Disease and people with amnesic mild cognitive impairment. Regression provided evidence that familiarity was more closely correlated with extra-hippocampal medial temporal lobe structures while recognition was more closely correlated with hippocampal volume. It will be interesting to see further research using different approaches to investigating this relationship. The authors of one study report progress in the use of radiolabelled iodine-123-metaiodobenzylguanidine scintigraphy in Lewy Body dementia (Treglia et al, 2010). There is a commentary on an association between Alzheimer’s Disease and seizures here. Four papers in the Lancet examining the relationship between blood pressure variability and stroke are reported on in this article.
Two recent studies reported on here have provided evidence that variations in the expression of the gene for insulin-degrading enzyme are associated with risk for Alzheimer’s Disease which is thought to be mediated via the degradation of Amyloid Beta plaque. Thus higher levels of IDE were associated with reduced risk. There is a report on a relatively small study (n=35) which investigated the relationship between family history and amyloid plaque accumulation identified using a combination of Pittsburgh B compound and PET scans. Research in fruit flies has shown the efficacy of a compound – affibody – in both degrading and facilitating removal of ABeta aggregates. One research group has identified a novel pathway involving amyloid plaque mediated excitotoxic cell death in a model of Alzheimer’s Disease which may lead to new therapeutic approaches. There is evidence that build up of Amyloid Beta leads to cataracts in people with Down Syndrome as well as being associated with early onset of Alzheimer’s Disease.
The Alzheimer’s forum (AF) has an interesting post on the relationship between metabolic disease and Alzheimer’s Disease (AD). There is a recent meta-analysis looking at the use of augmentation with acetylcholinesterase inhibitors in schizophrenia and schizoaffective disorder involving six open-label and 24 double-blind RCT’s with the authors showing benefits for memory and performance on the Trail Making Test Part A (Ribeiz et al, 2010) . The authors of a systematic review in the Journal of Neurology, Neurosurgery and Psychiatry concluded that MRI determined white matter hyperintensities had heterogenous pathological correlates and that developing quantitative MRI methods could enhance yield of clinical data. The International Working Group for New Research Criteria for the Diagnosis of Alzheimer’s Disease (AD) have published a paper in the Lancet Neurology in which they propose broader criteria for diagnosis in the research setting. A small study produced no evidence of an association between AD-related olfactory deficits and Amyloid Beta load using PET with Pittsburgh B compound. There is an interesting case study describing cobalamin deficiency associated executive dysfunction improving with replacement therapy. A recent study showed a significant difference in visual impairment between those with and without subsequent dementia (n=625) although it will be interesting to see if there is a causal link or else explanatory confounders.
A group in China investigated the possible role of the cerebellum in mild cognitive impairment. They compared 26 people with amnestic Mild Cognitive Impairment with 18 controls. Both groups underwent resting state fMRI at baseline and follow-up (at least 20 months later). Those with aMCI were significantly more likely to exhibit a higher amplitude of low frequency variation in the posterior cerebellum. The cerebellum has received little attention relative to cortical areas in MCI and it would be interesting to see further work in this area. At the Alzheimer’s Forum, there is a write-up of a study providing evidence that circulating Amyloid-Beta peptide may be deposited in the brain leading to Amyloid deposition which according to the Amyloid hypothesis leads to Alzheimer’s Disease. This contrasts with other models in which the disease is thought to occur when there is a disruption of clearance of the peptide from the brain into the circulation. A comparison (n=13734) of concurrent antipsychotic prescribing with Donepezil or Rivastigmine found a small (1%) but statistically significant difference with a lower prescribing rate in the latter although the interpretation is less than straightforward. A small study (n=43) provided evidence of hyperacusis (14%) and tinnitus (19%) in Semantic Dementia which the authors interpreted as possibly related to cortical changes identified using structural MRI although there was no control group in the study. A longitudinal Swedish twin study looked at predictors of developing dementia and identified grip strength and ‘higher emotionality on the EAS Temperamental Scale’ as significant predictors. A small Japanese case control study (n=89) showed evidence of a significant association between Thyroid Stimulating Hormone levels and right Cerebral Blood Flow in Alzheimer’s Disease and it will be interesting to see further research in this area. Researchers in a Brazilian study used texture analysis (TA) on MR images to identify differences between people with Alzheimer’s Disease and amnestic Mild Cognitive Impairment in the area of the corpus callosum and thalamus. Level of education was correlated with performance on the Clock Drawing Test in this South Korean study (n=268). A small study compared people with Frontotemporal Dementia, Lewy Body Dementia, Alzheimer’s Disease and controls and found a prevalence of occasional microbleeds in the control group of 60% as well as a signifiantly higher prevalence within the Alzheimer’s Disease group. Arterial hypertension was the most common risk factor in Alzheimer’s Disease and Lewy Body Dementia. There is an interesting paper on the possible non-progressive nature of behavioural variant Frontotemporal Dementia. In an evaluation of 522 patients who underwent subthalamic deep brain stimulation for Parkinson’s Disease the mortality occurred in 0.7% of cases. Adverse hardware events occurred in 7% of cases and the researchers concluded that deep brain stimulation ‘can be considered as a safe procedure’.
At the Alzheimer’s Forum there is a document outlining the work of the Michael J Fox Foundation which has established a multicentre study to investigate the biomarkers that could usefully predict progression of Parkinson’s Disease – The Parkinson’s Progression Markers Initiative. The approach is analogous to that of the Alzheimer’s Disease Neuroimaging Initiative and the researchers are focusing on alpha-synuclein, DJ-1, ABeta peptide, blood urate levels and CSF tau. There’s an interesting study looking at frontal lobe symptoms in people with (probable) Alzheimer’s Disease (AD), Lewy Body Dementia (LBD) and Frontotemporal Dementia (FTD). The sample size is large (n=559) with the global deterioration scale being used to assess severity and the Middelheim Frontality Score being used to assess frontal lobe function. The researchers found that AD and LBD severity were significantly associated with increasing Middelheim Frontality scores but the same relationship didn’t hold for FTD. However Middelheim Frontality score was significantly higher in the FTD group than for the other two groups regardless of severity. In the research setting this might be useful in further characterising the pathology of AD and LBD as the illnesses progress and it would be interesting to see further work investigating the association with behavioural changes.
There is a recent report from the longitudinal German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe) on anticholinergics in which the researchers cite a hazard ratio for dementia of 2.081. The study recruits people over the age of 75 and there are more details here. It will be interesting to see further work in this area and the implications may be complex and dependent on comorbidity but are also relevant to the Beer’s Criterion. In a murine model of abnormal amyloid deposition, the researchers found that interrupting the pathway between entorhinal cortex and hippocampus was associated with a lower deposition of plaque. There is a write-up at the Alzheimer’s Forum and the inference is that A Beta peptide is transmitted through synapses and in the comments it is noted that a constant supply is required to maintain plaques. There was a recent conference on Frontotemporal Dementia which is reported on at the Alzheimer’s Forum and includes interviews with some of the participants. There’s further research looking at bilingualism and onset of dementia. There is a brief write-up at the Alzheimer’s Forum of a cross-sectional study showing an association between an older age of onset of dementia and bilingualism. Those who were bilingual had symptoms of dementia 5 years later on average than those that were monolingual. However because this was a cross-sectional study it does not establish causality and so there may be other factors which account for this relationship. Additionally it’s not clear if people can learn a second language in mid-life and still gain the benefits as people in this study were bilingual from early adulthood.
A small EEG study comparing subjects with probable Alzheimer’s Disease with controls showed evidence of an increase in left intra-hemispheric and left parieto-temporal central coherence and a decrease in right temporo-parietal-central coherence in people with probable Alzheimer’s Disease compared to the control group. These differences were interpreted as alterations in cortical connectivity resulting from the disease process. A small study compared dental health in people with Alzheimer’s Disease with controls. The researchers found that people with Alzheimer’s Disease were more likely to leave their dentures in at night-time and that 70% of the people with Alzheimer’s Disease had irregular brushing of their teeth and cleaning of their dentures. A small FDG PET study found that people with vascular patients with dementia were more likely to have metabolic disturbances in the frontal lobes and deep nuclei than vascular patients without dementia. The authors of a systematic review on personality changes in Alzheimer’s Disease found decreases in conscientiousness and extraversion amongst other changes. A brief report on progress in therapy for Alzheimer’s Disease has been published at the Journal of Alzheimer’s Research and Therapy. The authors summarise different strategies being pursued currently including those targetting the Amyloid-Beta peptide.
A longitudinal study (n=3494) examining the relationship between caffeine intake and subsequent dementia found that there was no significant association between caffeine intake and forms of dementia including Vascular and Alzheimer’s Dementia. There was found to be a significant difference between those in the lowest and highest quartiles of caffeine intake with those in the highest quartile having a lower number of dementia associated brain lesions at post-mortem. In an article freely available here, researchers detail the post-mortem findings on the first person with Alzheimer’s Disease to undergo PET scan imaging with Pittsburgh B compound. The researchers found a strong correlation between the PET findings and the occurrence of plaques but not tangles at post-mortem. Thus this study lends support to the benefits of Pittsburgh B compound in the assessment process although there are limitations on the conclusions that can be drawn. In a study including 214 subjects – young, middle-aged, older adults and people with Alzheimer’s Disease the latter group were differentiated by performance on a visual motion processing task in which randomly moving dots were presented in the visual field. It will be interesting to see the results of further studies in this area.
A recent paper in the Lancet Neurology reviews developments in behavioural variant Frontotemporal Dementia including a new classification scheme which is characterised by the likelihood that the disease is correct. The September issue of the International Journal of Geriatric Psychiatry looks at national dementia strategies in a number of countries. The authors of a systematic review (open access) of studies looking at communication between people with Alzheimer’s Disease and their caregivers concluded that one technique was particularly effective
‘the use of memory aids combined with specific caregiver training programs’
A small Japanese study showed evidence for factors influencing response to Donepezil including age (inverse), duration of executive dysfunction and time to diagnosis. These are interesting findings but again it would be good to see replication studies with large numbers. In terms of molecular pathology, a recent study from Japan shows evidence of a relationship between insulin resistance and amyloid plaque but not neurofibrillary tangle development. There is other research which has produced different results but there is a write-up of the study over at the Alzheimer’s Forum. After undertaking a systematic review, one group have called for the development of a multidomain rating scale for use in Alzheimer’s Disease and to monitor progress – the paper is open access. A small Brazilian study looked at the interaction between vascular and other risk factors and cognitive decline in vascular dementia. The researchers found that after controlling for vascular risk factors education was significantly associated with decline. This reinforces previous research suggesting that increasing years of education are a protective factor for dementia although the literature also shows that the relationship is complicated and that education influences the rate at which decline occurs.
The authors of a review article in the Journal of Neurology, Neurosurgery and Psychiatry recommend an increase in referrals for genetic testing in cases of EOAD (Early Onset Alzheimers Disease) and IPD (Inherited Prion Disease) on the basis of case ascertainment from two UK genetic testing centres. Higher (but not lower) T3 levels were associated with decreased performance on memory and visuospatial tasks in a small case control study involving people with Mild Cognitive Impairment and healthy controls. The results for other hormones were non-significant. Briefly white matter hyperintensities in parietal networks were associated with deterioration in executive performance in MCI, diabetes at baseline was associated with a higher prevalence of AD and VaD in this large prospective study, larger temporal lobe volume was suggested to be a protective factor for Alzheimer’s Disease when there is a large Beta-Amyloid load in this PET study and specific variants of the Alzheimer’s Disease associated genes CLU and PICALM were associated with cognitive performance in the ‘oldest old’ in this study.
This report highlights recent research findings on biomarkers for Alzheimer’s Disease http://bit.ly/a43CnZ. Names influence career choice in children http://bit.ly/avw4sH. Study -prior brain size not atrophy related to cognition in community dwelling older adults – open access http://bit.ly/dfOVJ8. Ginko Biloba in dementia – meta-analysis shows efficacy compared to placebo – open access http://bit.ly/99m3b8. Diffuse Tensor Imaging was useful in discriminating between amnestic Mild Cognitive Impairment (MCI) and non-amnestic MCI in this moderately sized study (n=418). A structural 3T MRI study (n=50) examining age associated changes in the hippocampus identified these changes in the subiculum but found no evidence in other subfields. CSF levels of Beta-Amyloid were inversely associated with years of education in this study which recruited 70 people with a diagnosis of Alzheimer’s Disease. Links between DISC1 and APP gene products were identified in this study. The write-up is very good and essentially this research suggests a link between genes associated with Schizophrenia and Alzheimer’s Disease respectively. The functional links were identified in a neurodevelopmental model and involve interactions of the gene products during migration of neurons. On the basis of their findings the researchers hypothesise that the Amyloid Precursor Protein (APP) acts as a scaffold that interacts with the DISC-1 protein to facilitate migration. The role of the APP in Alzheimer’s Disease is different and so this study is not suggesting a link between the diseases although it is becoming clear that these two proteins have important biological functions.
A small PET study (n=42) using 18F-FDG to assess brain metabolism compared people with amnestic mild cognitive impairment with or without awareness of amnesia. The researchers concluded that hypometabolism in the inferior parietal lobule, superior temporal gyrus and angular gyrus were associated with loss of awareness (anosognosia) of amnesia although it would be interesting to see replication with a larger sample. A small structural imaging study recruited 11 people with PSEN1 mutation associated early Alzheimer’s Disease and compared with 18 controls. The researchers found that there was an increase in cortical thickness in the parietotemporal area and precuneus together with an increase in the caudate volume 9.9 years before the age at which onset was predicted. There followed a period of atrophy. This is a small sample but the study generates a very clear hypothesis. Free and delayed recall were associated with atrophy in the CA1 subfield of the hippocampus in this cross-sectional structural MRI study in 35 people with Alzheimer’s Disease. A post-mortem study compared a sample with Alzheimer’s Disease (n=10) with a control group (n=10) and the researchers found that when examining the microvasculature there was a significant association between increasing capillary length density (length per unit volume) in the temporal cortex and decreasing cortical diameter in this region. A longitudinal study is needed to investigate this further.
The authors of this paper make a number of suggestions about post-operative cognitive decline including a focus on codifying episodes. A large prospective study (n=3824) investigated the relationship of untreated and treated hypertension. The relative risk of dementia incidence with untreated hypertension was 1.9 compared to 1.5 in the drug treated group and relative to a control group who did not develop dementia. There’s a write-up of a recent study which showed a strong correlation between biomarkers and scores on a family/carer rated questionnaire (AD8) for function in people with Alzheimer’s Disease. A study appearing in the International Journal of Geriatric Psychiatry looked at prescription of antipsychotics in the last 90 days in people living in the community or in care homes in England and Wales by analysing a primary care database. 3677 patients were identified in the community and 2173 in care homes. Antipsychotic prescription was 0.9% in the community and 20.9% in the care homes in the last 90 days although these figures are not contextualised (e.g. the reason for prescriptions). Banerjee’s report on antipsychotics came at the end of 2009 (see here) and it would be interesting to see the figures in 2010.
Study shows association between depression and dementia – others also do although the relationship is complex http://bit.ly/bNKIXn.Percentage thickness changes in the inferior temporal and right fusiform cortices at six-months were associated with reduction in memory performance in this relatively small study (n=142) of older adults. There is a review article here on the three newly classified variants of primary progressive aphasia. A test of olfaction was used to discriminate between performance in people with Alzheimer’s Disease and Mild Cognitive Impairment (MCI) in one study. Optimal unirhinal performance did not discriminate between AD and MCI although suboptimal performance did. There is a review of treatment of sleep disturbances in Alzheimer’s Disease in the International Journal of Geriatric Psychiatry covering non-pharmacological treatments including Bright Light Therapy as well as pharmacological treatments. The authors conclude that more research is needed in this area. There is a write-up of a study which used susceptibility-based MRI to investigate differences between MCI. This imaging technique is effective for investigating the cerebral vasculature and the researchers found evidence of microhaemmorhages in people with MCI compared to a control group. Further research shows an association between adult central adiposity and later life dementia in this study of community residents (n=700). There is a literature review comparing memantine and ACHEI’s tolerability data here.
There was a small study which involved comparing post-mortem examinations of the brains of people who had Frontotemporal Lobar Degeneration (FTLD) and Alzheimer’s Disease with a control group. The researchers concluded that there was a decrease in the protein SNAP-25 in the FTLD group. The group also found that SNAP-25 levels were further decreased by the presence of the APOE4 epsilon 4 allele. The researchers in a small Positron Emission Tomography (PET) study and part of the Osaki-Tajiri project found that administration of Donepezil was associated with both an improvement in visual hallucinations in 50% of participants as well as a reduction in metabolism in the medial occipital cortex in subjects with Lewy Body Dementia. The relationship between acetylcholine and visual hallucinations in other disorders has been discussed elsewhere and it will be interesting to see further replication of this work particularly in terms of the localisation of hypometabolism.
There has been some positive news in Frontotemporal Lobar Degeneration (FTLD) research with two groups independently identifying the role of an FTLD related gene – progranulin in binding to a cell surface protein – Sortilin. There has been a recent PNAS study involving researchers from several institutions looking at the effects of Metformin on Alzheimer’s Disease associated neurofibrillary tangles in mice. The researchers found some evidence that Metformin interfered with tau phosphorylation and that it might have a prophylactic effect against the development of tangles. However it will be interesting to see the results of clinical trials. A post-mortem study examined dementia in the oldest old (90-103 years of age). The researchers correlated Clinical Dementia Rating (CDR) scores with neuropathological findings. They found that with the younger population there was a significant correlation between diagnosis of dementia and a combination of rating of severity of white matter lesions, Braak staging and presence of Beta Amyloid protein deposition. These three factors predicted only 30% of the variation in the CDR scores however.
A small structural MRI study (n=68) looked at the relationship between scores on a neuropsychological test battery (CERAD) and cerebral correlates in 60 people with Mild Cognitive Impairment, 34 people with Alzheimer’s Disease and 32 controls . The researchers found that performance on certain memory tasks (immediate and delayed recall) was significantly correlated with grey matter density in several areas rather than one suggesting these functions had cortical network correlates. The Alzheimer’s Forum have a four part series on a London conference examining research trials for autosomal dominant Alzheimer’s Disease and Huntington’s Disease. Participants at the conference were particularly interested in how drugs targetting amyloid plaques could be used prophylactically in the presymptomatic phase. There was also discussion of how biomarkers could be useful in evaluating disease progression in research trials. The report also draws attention to the Dominantly Inherited Alzheimer’s Network.
Schizophrenia
A recent relatively small study in the Archives of General Psychiatry looked at people with schizophrenia (n=8) and compared them with controls (n=8). They used structural imaging to compare the hippocampal volume after a program of aerobic exercise. There was found to be 12% increase in hippocampal volume in the people with schizophrenia and a 16% increase in the control group adding to the evidence base for the benefits of exercise in both health and illness (see also the book reviewed in this post). There is a special edition of Brain Bulletin on Schizophrenia genes freely available here. This includes papers on the complex traits of schizophrenia and genome-wide associations. Electroretinography has been used to investigate healthy people with a family history of schizophrenia or bipolar disorder and the researchers have found preliminary evidence of a reduction in the responsiveness of the rods in the retina. They compared 29 people with a family history of either Bipolar Disorder or Schizophrenia with 29 healthy controls without a family history of these disorders. They found a significant difference on one of the amplitude measures (23%)(p<0.0001). The researchers interpreted this as suggesting a possible genetic basis for an alteration in the early stages of sensory processing. However it will be interesting to see if these findings are replicated in larger studies and if so then it will complement other lines of evidence showing a relationship between altered perceptual (rather than sensory) processing in the cortex and psychopathology.
Some people with epilepsy may develop psychosis between seizures – interictal psychosis and the prevalence varies between 0 and 16% (Trimble, 1991)(Umbricht et al, 1995). In a Japanese study published in the British Journal of Psychiatry 285 people who had developed both epilepsy and interictal psychosis were assessed (Adachi et al, 2010). The researchers found that the time interval between onset of epilepsy and interictal psychosis displayed a skewed distribution (to the left i.e closer to the onset of epilepsy). The researchers were also able to better characterise the relationship between interictal psychosis and epilepsy in their sample. Thus a family history of psychosis was associated with earlier onset of interictal psychosis as were the generalised forms of epilepsy. The researchers conclude that there were independent risk factors for both epilepsy and interictal psychosis as well as possible shared risk factors.
A widely reported study (e.g see here and here) looked at a murine model of schizophrenia and the researchers provide evidence of a neural substrate for the association of chromosome 22q11 with schizophrenia. The researchers found that the deletion was associated with a disconnection between the hippocampus and the prefrontal cortex. It will be interesting to see if evidence of this disconnection is found in people with chromosome 22q11 mutations or deletions. An Indian group has conducted a randomised placebo-controlled trial of Olanzapine + Placebo v Olanzapine + Topiramate (n=72; 12/52; first-episode) in Schizophrenia showing a significant weight increase versus weight loss in the respective groups (Narula et al, 2010). These results should be interpreted in the wider context of the considered review process needed for local guidelines. A large study in Acta Scandinavica Psychiatrica (n=1213) compared people with early and late-onset schizophrenia against controls on a number of psychometric measures (Vahia et al, 2010). The authors write that
‘Early-onset schizophrenia and LOS groups differed from NCs on all measures of psychopathology and functioning, and most cognitive tests’
There were differences between the LOS and EOS groups and the authors concluded that Late-Onset schizophrenia should be considered as a subset of schizophrenia. An american study used a grounded theory approach to investigate the responses of 12 African-American families to treatment of a family member with psychosis. The authors identified a number of themes and concluded that
‘The findings suggest that due to fear of the official label of a mental illness, certain coping mechanisms may be adopted by families, which may result in a raised threshold for treatment initiation’
The authors recommend further research and suggest that this may influence future public education campaigns (Franz et al, 2010). There is a small case series (n=2) showing the effective use of fluvoxamine in the treatment of aripiprazole-induced akathisia perhaps warranting a randomised-controlled trial or pilot study (Furuse et al, 2010). Over at the Schizophrenia Forum, the schizophrenia gene database has just been updated with new features including methods for visualising the data. There is coverage of a study providing evidence of a relationship between the DISC-1 and NRG-1 genes both of which are associated with schizophrenia. The research also shows that DISC-1 is expressed in glial cells and the significance of this is discussed further in the article.
The researchers in a 5-year prospective study published in the British Journal of Psychiatry examined people with schizophrenia or bipolar depression or both, with and without diabetes. For those with diabetes the hazards mortality ratio for schizophrenia was 1.84 (95% CI 1.42-2.40) and for bipolar disorder was 1.47 (95% CI 1.07-2.02). This emphasises further the importance of recognising physical and mental illness comorbidities and this has been the focus of various studies and initiatives. Studies such as these can be helpful in evaluating and influencing such initiatives. A comparison of 56 older adult marathon runners (>60 years) and an inactive control group (n=58) using a neuropsychological test battery (CERAD and Vienna neuropsychological test battery) found a significant improvement on only the five point test for the marathon group. The marathon group did not show increased BDNF levels which has been associated with exercise. However this was a cross-sectional study and a longitudinal cross-over design might offer other insights into the relationship between running and cognition in older adults. Other test components were correlated with single areas. One study examined the experience and opinions of psychiatrists on drug-drug interactions for oral antipsychotics while a large study (n=18,154) compared the incidence of adverse events for Ziprasidone and Olanzapine. Current Directions in Psychological Sciences have an open access edition focusing on Schizophrenia here while there is an open-access review of Aripiprazole in the treatment of late-onset schizophrenia here.
Research in Alcohol Dependence
In research into the treatment of alcohol dependence, there has been found to be a strong relationship with Corticotrophin Releasing Factor in a murine model. A number of antagonists of CRF were successful in alleviating alcohol dependence related behaviours and it will be interesting to see the results of human trials.
Research in Mood Disorders
There are preliminary reports that a proprietary combination of Buspirone and Melatonin – BCI-952 is effective in people with depression on the basis of a 6-week trial (n=142) with various outcome measures although this is a press release and it will be useful to see the study in more detail when it is formally published. The significance of this is that the combination has been shown in vivo to stimulate neurogenesis which is hypothesised to be a mechanism of antidepressant action. There is a write-up of a longitudinal study comparing women with depression who were placed on a treatment program focusing either on weight loss or weight loss and treatment of depression. The researchers found that women in the latter group had significantly more weight loss than those on the former program. There’s another paper from the Journal of Clinical Psychiatry that looks at potential future antidepressants that are in the early stages of research and from the following classes
– Serotonergic drugs
– Triple uptake inhibitors
– Glutamergic drugs
– Neurokinin based interventions
– Antiglucocorticoids
– Neurogenesis based drugs
– Nicotinic agents
Drug trials can be found at the Clinical Trials register (see here) where for example a Phase 1 trial of the neurokinin 1 receptor antagonist GSK424887 has just been completed. There is a small 6-week study (n=54) in the Journal of Clinical Psychiatry examining the use of valproic acid in people with Bipolar Disorder I or II depression. This is a double-blind randomised placebo controlled trial with the valproic acid group associated with 38.5% v 10.7% (placebo) of subjects meeting response criteria (p=0.017 0.17). Depression was assessed using the MADRS although the difference in remission rates (rather than response criteria) has a p-value of 0.208. There is a report here on a recent study in Biological Psychiatry (see here) showing evidence of decreased time to remission of depression in a trial of Scopolamine compared to other classes of antidepressants. Scopolamine is a muscarinic antagonist and the tricyclic antidepressants also act on these receptors in contrast with the SSRI’s. There were 23 subjects in this double-blind placebo-controlled cross-over trial and there was both a statistically significant improvement (p=0.001) and clinically significant improvement (32% reduction in MADRS scores compared to 6% in the placebo in the first phase of the study.
An economic analysis of a stepped-care model of prevention of anxiety and depression in older adults showed that the incidence could be halved and a costing per depression-free year was calculated (Harm van Marwijk et al, 2010). The study was performed in the Netherlands and included older adults over the age of 75 (n=170). The stepped care model included ‘watchful waiting, bibliotherapy, problem-solving treatment and antidepressant medication’ following a mailing of the Centre for Epidemiological Studies Depression scale (CES-D) to the patient and follow-up call. There is a write-up of a Nature Medicine study involving post-mortem whole-genome tissue scans in 21 people who had been diagnosed with depression and 18 controls and finding a 2-fold increase in the MKP-1 gene product in the brains of the depressed group. MKP-1 has associations with neuronal survival. A JAMA paper outlines details of a successful suicide reduction program in people with depression. In this population, the suicide rate was reduced by 75% and over a 2.5 year period was 0.
In the online version of the Journal of Clinical Psychiatry there’s an interesting study on factors associated with good ECT response in older adults (Oudega et al, 2010). This a naturalistic cohort study with a sample size of 81. The authors found that while white matter hyperintensities or global atrophy weren’t associated with differences in response, Medial Temporal Lobe atrophy (MTA) was. On the Montgomery Asberg Depression Scale, MTA was associated with an almost 50% reduction in response compared to those without MTA and this was significant at the 1% level. This is interesting in terms of other research suggesting an association between ECT response and an increase in hippocampal volume (as in this small study) as well as other research suggesting a role for various nerve growth factors. Nevertheless it would be good to see further replication of these findings and it would be particularly interesting to look at what happens to hippocampal volume (if anything) after treatment in a similar sample population.
Sleep
In a small study (n=18) researchers found that sleep deprivation was associated with a slowing in speech as well as a reduction in the variation of tone. There’s a write-up here of another study looking at sleep in African and Hispanic Americans (n=1107) and finding an association between sleeping either less than six hours or more than 8 hours a day and the accumulation of visceral fat. The study was published in the journal Sleep (see here) and was a longitudinal cohort study with various measurements at 5-year intervals. These findings are potentially important in view of other research showing increased mortality in groups with this amount of daily sleep compared to those who sleep between 6 and 8 hours daily. This new research is examining the pathways involved and in turn this information can be potentially useful in stratifying risk although this would require further research.
Neurotic, Stress Related and Somatoform Disorders
This is an interesting idea. One developer has produced an ‘anti-stress’ pen that detects the movement of the user’s hand and analyses this for evidence of ‘anxiety associated’ movements. The pen is able to provide feedback to the user. Breathing exercises are an effective way to manage anxiety attacks. One study (n=41) has demonstrated an advantage for feedback on carbon dioxide levels using a capnometer when compared to cognitive therapy. This is referred to as Capnometry Assisted Respiratory Training or CART for short. The researchers in a study using Magnetoencephalography looked at a group of US Veterans with Post-Traumatic Stress Disorder (PTSD)(n=74) and a group of controls without PTSD. They identified a characteristic signal in the people with PTSD using what they refer to as the ‘synchronous neural interactions test’. The distinction between this biological marker and a diagnosis of PTSD is discussed over at MindHacks. The authors of a PLOS one study examined flashbacks after presentation with distressing images. Subjects were also asked to take part in either a game of Tetris which involved visual memory or a verbal memory task. They found that those who played Tetris were less likely to experience flashbacks after presentation of the images than those engaged in verbal memory tasks. The researchers suggest that playing Tetris may be useful in preventing PTSD although the events leading to PTSD are considerably different (in the DSM-IV diagnostic criteria) from the research paradigm.
Dyslexia
In a small structural and functional imaging study researchers identified the right frontal region as an important area in differentiating between children with dyslexia associated with improvements in reading over time. This was based on both the functional and structural (diffuse tensor imaging) findings. However it will be interesting to see larger replication studies.
Personality
In the British Journal of Psychiatry, there is a systematic review of pharmacotherapy for Borderline Personality Disorder (Lieb et al, 2010). The researchers identified pharmacotherapy studies of people with a DSM-III/DSM-IIIR/DSM-IV/DSM-IV-TR diagnosis of Borderline Personality Disorder. They included studies which allowed for pooling of effect sizes and grouped the symptom clusters into interpersonal problems, impulsive-behavioural dyscontrol, cognitive-perceptual symptoms and affective dysregulation. In these four clusters, the researchers were able to find clinically and statistically significant effects for specific psychotropic medications which are outlined in the article. They note a number of limitations including the exclusion criteria in the original studies meaning that in a number of studies there may be differences from a clinical sample of people with a diagnosis of Borderline Personality Disorder. They conclude from their study that on the basis of their evidence pharmacotherapy can be directed at symptom clusters and they suggest that their findings can be of relevance to any revisions of APA and NICE guidelines.
Autistic Spectrum Disorders
The use of copy number variants in Autistic Spectrum Disorders is reported on here. There are results from a preliminary study involving the use of Oxytocin in people with Asperger Syndrome. The researchers concluded that there was evidence of increased responses to social cues including the degree of cooperativeness of other players in a ball game. However this was a small study with 13 subjects and it will be interesting to see the results of larger replication studies.
Neurophysiology
There is a write-up of an fMRI study in which volunteers were asked to respond to picture of facial expressions with words superimposed. The researchers found that the subjects would respond less quickly to the words if they were incongruous with the expressions on the faces (e.g the word sad superimposed on a happy face). The researchers also found that when this occurred there was corresponding activity in the left inferior frontal cortex and inferred that this is where inhibition of automatic responses occurred. What is interesting about their finding is that it may lead to insights in another area. Some people with schizophrenia experience what is known as incongruity of mood – they might laugh when they are feeling sad. These findings might be useful in generating a hypothesis about why this might be so.
Neuroscience
Being ‘connected’ with your image of a future self was associated with saving money for the future in one study described here. There’s a discussion of motion sickness in virtual reality settings here. In a small study it was found that the silhouette illusion – an illusion where rotatory movement is perceived – the response is not associated with handedness or personality type. In a very interesting study researchers used two-photon microscopy to observe synapse formation between neurons. Their observations led them to conclude that neurexins were integral to the process of synapse formation.
In a recent well-publicised New England Journal of Medicine study, researchers have found an has been the association of between expected brain activity with and answers to questions about familiar topics in a person with a previously clinically recognised vegetative state. There is coverage of the study here which includes a video showing the location of brain activity in the visualisation tasks in a demonstration. The original paper is here and the supplementary paper is here. This was a continuation of previous research in this area a few years ago. The researchers used fMRI with a 3T scanner in two European sites. The controls and the subjects were asked to visualise themselves hitting a tennis ball or walking from room to room in their home while visualising the scenery.
These two tasks activated the supplementary motor area (SMA) (motor task) and parahippocampal gyrus (PHG) (spatial task) respectively. The researchers then asked all subjects to associate the motor task with yes and the navigation task with no. They were careful to ensure that the subjects attended to these tasks with a period of sustained attention so that the signal could be distinguished from that associated with more automatic responses. This was done in order to increase the likelihood that the activity represented ‘conscious’ activity. The tasks were repeated on 5 occasions to increase the reliability of the data after averaging the signals. They then presented subjects with autobiographical questions. I wasn’t clear on whether the questions varied from one subject to another. They were then asked to think the correct response – a yes or a no by means of the associated imagery. The researchers averaged the activity for the imagery tasks. They averaged the activity for the responses to questions. They identified the ‘centre’ of the activity for both tasks and calculated the distance of the centres of activity from each other to produce a ‘similarity’ score. The ability of a person to produce activity in the SMA or PHG in response to the researcher’s instructions was inferred as evidence of the will (although perhaps an interruption of auditory or semantic processing may interfere with task responses also). Of 54 patients in the study with a clinically recognised vegetative state, in 5 of those people activity in the appropriate areas were associated with the researchers’ instructions on the imagery tasks. However when it came to the autobiographical questions, only 1 subject produced activity associated with the correct responses. In this subject the expected activity for correct responses was identified in 4 out of 5 of the autobiographical questions.
What was interesting here was that as well as averaging group activity and comparing groups, the researchers focused on the individual results. Perhaps this was necessary as there was only one subject with the anticipated evidence of ability to respond to questions. I wasn’t clear on what the researchers’ thoughts on the ‘incorrect’ response was and which method was used for controlling for multiple comparisons (this time it’s a slightly different type of multiple comparison to that discussed in a previous paper reviewed here) as the tasks were administered to 54 subjects with the above results. It will be interesting to see further results in this area and if this approach proves successful then there may be other conditions which it might be applicable to where there are similar difficulties with communication.
Miscellaneous
Researchers recruiting subjects for clinical trials in rural areas have provided evidence that the use of specific metaphors are better than others and that the concept of randomisation can be misunderstood with some metaphors. Researchers conducted a large study on face recognition which provided evidence that face recognition peaks at between 30 and 34 years of age. Professor Richard Williams, is interviewed in this article and discusses some of the effects that the earthquake might have on children in Haiti and approaches to responding to this. The Psychiatric Bulletin familiar to British Psychiatrists has been renamed ‘The Psychiatrist’ and includes articles submitted by allied mental health professionals. There are 2 interesting articles on the recovery model as well as a meta-analysis of low and high-dose quetiapine. The latter article looks includes two studies (combined n=175) and concludes from the evidence that low and high dose quetiapine show equal efficacy in schizophrenia on outcome measures including positive symptom score on the Brief Psychiatric Rating Scale although these were 6-week trials (Painuly, 2010). There is another interesting article by a nurse and psychologist team reviewing the standard community mental healthcare for people with severe personality disorder. The researchers were interested in the standard management against which other treatments were compared and conclude by recommending further empirical evidence for the standard approach (Koekkoek et al, 2010).
There is a very interesting article in ‘The Psychiatrist’ about the identity of psychiatrists or more specifically the areas of core expertise (Craddock et al, 2010). Craddock and colleagues propose 9 core attributes of the psychiatrist which include a broad biopsychosocial perspective, using a broad knowledge of biology and ‘clinically relevant aspects of neuroscience’ as well as advocating for people with a mental illness. In a small, preliminary study (n=9) looking at the use of blueberry juice on memory there was a significant improvement on a test of paired associative learning and word list recall at 12-weeks in older adults with ‘early memory changes’. However this will need to be replicated preferably over a longer time period and in a well characterised and larger population with randomisation, blinding and a control group. While blueberries are noted to have strong antioxidant properties, the authors suggest that it is the properties of the anthocyanins in blueberries which influences neuronal signalling which may relate to any beneficial effects. A development in electron microscopy is the use of electron cryotomography. This is the rapid freezing of biological materials to -140 degrees Celsius to preserve the positions of intracellular structures. This article looks at a study published in the Journal of Cell Biology using this technique. The authors note that filaments in the neuron constrain the activity of intracellular vesicles which contain neurotransmitters for release for example. This article looks at a study which investigated the effects of other people with varying degrees of self-control on a person’s own self-control in a variety of experimental scenarios. In these scenarios the researchers found evidence that finding evidence of self-control in others or thinking of those with ‘high’ self-control was associated with a higher degree of self-control in the subject.
There are further preliminary results on vascular decompression in Multiple Sclerosis and it will be interesting to see the results of further research in this area. The use of neuroscience in court cases was discussed at the annual meeting of the American Association for the Advancement of Science and a mock trial was staged and the associated complexities explored. A neurosurgeon commenting in the Journal of the American Medical Association has called for helmets to be used in skiing and snowboarding which to reduce the risk of head injuries in accidents. The authors of a Nature Neuroscience paper have found evidence that A-Type K+ channels and T-Type Ca Channels act together during action potential transmission. An fMRI study provided evidence of different regions involved in learning new verbs (left posterior temporal gyrus and left inferior frontal gyrus) and nouns (left fusiform gyrus) as well as a relationship between hippocampal activity and the efficiency of learning new nouns. This information could be of relevance to a number of conditions which involve disorders of language and memory. For more information on the study see here. A study involving neural prosthetic devices in people provided evidence of the function of the beta and delta oscillations identified in the EEG. Based on their findings about the timing of the oscillations, the researchers concluded that the beta oscillations were strongly associated with anticipating commands for initiating movements. For more information see here. Discover reports on some experimental evidence to suggest that smells and sounds are perceived together as hybrid ‘smounds’ – at least in a murine model. These conclusions are based on the activity of cells in the olfactory tubercle which respond not only to smells but also auditory tones presented alone or in combination with smells*.
There was a recent study (also covered here) in rats which found that suppression of Vasopressin secretion interfered with the ability of adult rats to recognise baby rats. This adds to other research from the same research group which suggests that Vasopressin may be involved in the formation of emotional memories which are important for social interactions. If this is replicated in humans then it would have application in social cognition which in turn is relevant to a number of conditions. In another widely reported study, a team have collected intestinal bacteria from a sample of 124 European subjects and sequenced the genomes of the 160 bacteria identified. The resulting genomes when combined into a ‘metagenome’ are larger than the human genome and the significance of this for human illnesses will surely become clearer with time. There is a fascinating look at a study investigating how ‘fast food’ may generate psychological responses that modify behaviour at ‘We’re Only Human’. The subjects in the study were asked to look at a computer screen and solve a task while very rapid images of fast-food related symbols were flashed up in the periphery. When these symbols were presented (priming) the subjects would respond more rapidly and this was interpreted as they were feeling ‘time pressure where there was none’. There were additional stages in the experiment. When subjects were primed with the fast food symbols they would select more efficient household item designs e.g a four-slice toaster rather than a two-slice toaster.
Finally the subjects primed with the fast food symbols were more likely to accept a small amount of money in the present rather than delay acceptance of a larger amount of money. So the term ‘fast-food culture’ takes on a new meaning.
Wray Herbert looks at a new paper in which psychologist Ibrahim Senay investigated wilfulness and willingness. He used an anagram paradigm:-
‘But before starting this task, half the volunteers were told to contemplate whether they would work on anagrams, while the others thought about the fact that they would be doing anagrams‘
The subjects who considered whether they would work on the anagrams completed more anagrams than the other group. The experiment was altered slightly and subjects wrote one of two phrases
‘Some wrote the words I Will over and over, while others wrote Will I‘
Again, the group that wrote ‘Will I’ completed more anagrams. The same results occurred when applied to exercise. The subjects were more likely to experience guilt if they willed themselves to complete the anagrams in contrast with those who questioned whether they would. Senay interpreted the latter group as being intrinsically motivated. So if these results generalise, this would suggest that questioning whether to engage in a task will be more effective than goal setting although it would be interesting to see further results in this important area.
Aaron Saenz covers a recent study on facial recognition in twins utilising a number of relevant tasks one of which is demonstrated in the article. The findings showed a 0.7 correlation of scores in identical twins compared to a 0.29 correlation in non-identical twins and thus support a strong genetic component for facial recognition. Dr Grohol tackles the recent New York Times article on psychiatry and draws his own conclusions. The Neurocritic refers to a paper by Carl Friston relating his concept of free energy to a number of Freud’s concepts in a recent paper he has published. Sandy Gautam looks at a remarkable paper on the C.Elegans nematode in which the researchers are able to predict 95% of the variance in the shape of the worm using a simple model. While people are many orders of magnitude more complex than C.Elegans it is a useful proof of principle and suggests that perhaps much further down the road a predictive model of human movement based on neural pathways and physiology may be feasible (there are many developments in this area already particulary in the area of neural prosthetics) which would have applications in a number of conditions. Karen Sternheimer analyses a recent meta-analysis that examines the relationship between violence in video games and aggression in children and gives her justifications for rejecting the author’s conclusions.
In a widely reported BMJ study, the use of checklists – care bundles – for 56 conditions was associated with a marked reduction in mortality rates at a North London NHS Trust. There is coverage of a paper here which suggests that linking Electronic Healthcare Records with DNA databases can accelerate the identification of relationships between genes and disease. The UK government has set aside an extra £2 million for funding mental health services for war veterans to be allocated to a range of services including community psychiatric nurses, GP training and helplines. A widely reported neuroimaging study provided evidence of frontal cortex activity being divided between hemispheres for two tasks compared to one. Additionally the authors concluded that there was a deterioration in allocation of resources for more than two tasks. A small PET study shows evidence of hypometabolism in the Superior Temporal Gyrus in people with Temporal Lobe Epilepsy (TLE) with deja vu compared to healthy controls and people with TLE without deja vu. The authors of a paper in the open access journal Trials look at unpublished Stroke trial data which if published has the potential to influence practice. The insertion of artificially-synthesised DNA into a bacterial cell with subsequent establishment of viability has been widely reported in the media (see here, here, here, here and here) and will lead to substantial debate about the ethical implications as well as leading to a vast array of applications. An interesting soundbite from Venter’s presentation is
‘This is the first self-replicating species that we’ve had on the planet whose parent is a computer‘
One group has identified details of Lithium mediated anti-inflammatory pathways which may contribute to an understanding of Lithium’s mechanism(s) of action. The authors of this study have called for psychiatrists to be included in ‘disaster first-response’ teams on the basis of their findings. A group of physicists have predicted that the magnetic fields associated with ball lightning would be sufficient to stimulate phosphenes, visual experiences secondary to cortical activation which would likely influence the perception of lightning. Also an ambitious scientist is attempting to detail the wiring of the brain in what is referred to as the connectome project. There is a write-up of a Nature paper in which a research group demonstrated a change in Blood Brain Barrier permeability using pharmacological modification of pericytes. A merger between the National Prescribing Centre and the National Institute for Clinical Excellence is taking place and scheduled to complete by April 2011. The National Prescribing Centre informs Government on the economic implications of medication prescribing. There is a link to an interesting BPS article on ‘scientific discounting cognitions’ at this week’s Spike Activity at Mind Hacks. The article features a discussion with Professor Munro who has found that a person’s reception to new findings in science is influenced by their underlying values and the details are explored further in the article.
Ed Yong has an ‘missing links‘ article with interesting general science links and draws the readers attention to recent results from the 1000 Genomes Projection Consortium. There are more details on this at Nature and just to quote from the abstract
‘On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders‘
and also
‘From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10−8 per base pair per generation’
This first figures are really interesting. If we can generalise from this data to the wider population that we would each have about 300 genes that aren’t functioning (I wasn’t clear on whether these are inherited or if they are de novo mutations). Since mutations are the mechanism through which we become genetically differentiated, each mutation can produce a change which can lead to successful adaptations to the environment. Switching off a gene here or altering a gene there might in some way give a person a selective advantage that better enables them to pass on their genes. On the other hand there were an average of 50-100 genes that have been associated with ‘inherited disorders’. At the moment, the genome sequencing technology is not widely available and people might learn of an inherited disorder after clinical suspicion is raised and appropriate investigations are undertaken. However this technology will be widely available in 10 years time and we have to look realistically at the possibility that clinical practice will be transformed. Thus in ten years time, the general population might go to private companies to have their genomes sequenced, receive the results and then present to their doctors with a list of 50-100 variants asking for advice. This would have implications for primary and secondary care that will need to deal with both realistic and unrealistic expectations.
One paper that has been widely reported in the media (see here, here and here) is the use of transcranial magnetic stimulation in a group of students which was associated with improvements in performance on mathematics tasks. The paper is freely available here. This looks like a pilot study as the sample size is small (n=15). Five students were adminstered a current in one direction across a region including the parietal lobe, another group received the current in the reverse direction and a third group acted as controls receiving a small current which was considered to have no effect. There were 3 tasks involving learning the value of symbols which must be discriminated according to magnitude, discriminating symbols according to size and mapping symbols to physical space. There were six training sessions over 7 days and the stimulation was applied during the course of the training session. There were clear and significant advantages for one treatment group over the controls in the symbol learning task but in the other tasks the results were complex and different learning effects were described in all three groups. The researchers have generated a clear hypothesis which has been reported widely in the media and it would be interesting to test this specific hypothesis with ‘real-world’ examples in a larger sample sufficiently powered to investigate the effects of age.
The researchers in a french study drew a number of conclusions about the ‘Activities of Daily Living Scale’ and suggested areas for improvement. The authors of a recent study looked at participants who had enrolled in a research register. They found that for older adult participants, transport was the biggest barrier to participating in the research.There is a write-up here of a study involving participants in their 20′s, 40′s and 60′s. The researchers found evidence that the older adult group were better at reappraising negative events positively but that the other two groups scored more highly on tasks that involved ‘detached appraisal’ in which events are viewed while dissociating feelings. Evidence for efficacy of tool that measures pain in non-verbal population – (open access) http://bit.ly/cTFLi7. A lady with panic disorder is reported to have spent 4 months in a hospital car park highlighting the morbidity that can be associated with this disorder. Slowed reading speed found with an e-reader v printed book in one study http://bit.ly/9VEf1H. There’s a write-up of some recent research which provides evidence that neurons form local and global networks through synchronous firing. There’s a write-up of another interesting study here in which the researchers provided evidence that career choice is associated with the brain region that undergoes atrophy in people with fronto-temporal lobar degeneration. The inference is that career choice will determine the nature of the work that is undertaken which in turn will determine the brain region which is regularly used although this relationship is unlikely to be straightforward. An fMRI study in 33 volunteers provided evidence that reduced activity in the dorsal striatum (associated with reward) in response to drinking a milkshake was associated with weight gain at six-month follow-up and the researchers hypothesise that overeating is associated with reduced pleasure from eating. In a study investigating volition, stimulating the left side of the brain with transcranial magnetic stimulation in 33 volunteers was more likely to lead to them ‘choosing’ to use their left hand in choice tasks.
The Frontier Psychiatrist has a very interesting interview with psychiatrist Dr Iain McGilchrist. Over at Psychotherapy Brown Bag there is a very interesting article on the relationship between experience and efficacy in psychotherapy. Professor Dunbar, who coined the Dunbar number has been looking at Facebook relationships. The Dunbar number – 150 – indicates roughly how many relationships people can manage effectively. Professor Dunbar followed up his earlier work by looking at Facebook and has suggested on the basis of his analysis that there is evidence that this number remains. Even when people have higher numbers of friends, they effectively manage the core group of about 150. He also found some gender differences in relationship maintenance. The Hawaii Medical Association is now offering patients virtual appointments with doctors and this will no doubt be followed with interest by other organisations. An american study looked at census data between the years 1990 and 2006 in the state of Virginia and concluded that socioeconomic status was strongly inversely associated with mortality and that if the mortality rates of the 5 most affluent states and cities were applicable throughout the state there would be a 25% reduction in mortality.
DSM-V
The draft changes for DSM-V have been published by the American Psychiatric Association Draft Development Team for DSM-V here. I might have overlooked something but it looks as though it is an overview of the changes being suggested for specific conditions that are being presented.
Firstly I was interested in what amounts to a wholescale reclassification of the dementias and related conditions into major and minor neurocognitive disorders. There are some nice ideas contained within this move including the consideration that it is not only memory which needs to be affected. However I was unclear on reading the descriptions of whether it would include the subtypes as I could find no mention of this. However it would be unusual if the various subtypes of dementia for which there is an abundance of evidence were not included as subtypes within this framework as this could be considered a step backward. Additionally I couldn’t find any mention of the term Mild Cognitive Impairment (although there are some broad similarities with minor neurocognitive disorder) and the various subtypes for which there is an emerging evidence base and which is the focus of research in the hope that a better understanding could lead to prevention or amelioration of subsequent dementia.
Mental Disorders Due to a General Medical Condition
There were very few changes here. One suggestion was to use a catatonia specified elsewhere instead of catatonia secondary to a medical disorder.
There are some big changes in the Personality Disorders. These have been reduced from 10 to 5. One of the difficulties with the current Personality Disorder types is the diagnostic overlap. A person may fulfill the criteria for more than one type of personality disorder. There are a number of changes to the criteria which should improve reduce the number of comorbid personality disorder diagnoses. A simple likert-scale is used for quantifying personality and personality traits and the five types are Borderline Personality Disorder, Antisocial/Psychopathic Type, Avoidant Type, Obsessive-Compulsive Type and Schizotypal Type.
There are a large number of new diagnostic labels being considered for inclusion and subsuming current labels. For instance alcohol dependence syndrome may be subsumed under alcohol-use disorder. Cannabis withdrawal is another diagnosis being introduced. The discussions around the terms ‘addiction’ and ‘dependence’ are discussed below.
Schizophrenia and Other Psychotic Disorders
There are big changes to the diagnosis of Schizophrenia with a proposal for removing subtypes including paranoid schizophrenia, disorganised and catatonic schizophrenia. Changes are being suggested in order to bring DSM-V into closer alignment with ICD-10. Proposed changes to the criteria for Schizoaffective Disorder are meant to increase reliability. ‘Psychosis Risk Syndrome‘ is being introduced (see further discussion below) and a Catatonia Specifier is being suggested. This is apparently because catatonia is ‘often not recognised’.
Mixed anxiety and depression disorder is being introduced with criteria that avoid ambiguity. This is currently included in the appendix of DSM-IV. There is a proposal to rename Dysthymic Disorder as chronic depressive disorder. There is a proposal to replace Bipolar Disorder Most Recent Episode Mixed with a mixed specifier. There are a number of changes in the criteria of Manic Episode particularly around energy levels.
The proposal is to include Obsessive-Compulsive Disorder under a new category of ‘Anxiety and Obsessive-Compulsive Spectrum Disorders’. The changes here are further discussed in the ‘PsychBrownBag’ Blog and the ‘OCD Center of Los Angeles’ Blog below.
There is a proposed amalgamation of four conditions into ‘Complex Somatic Symptom Disorder‘ but for further discussion see the ‘OCD Center of Los Angeles’ Blog below.
The proposal is to reclassify Factitious Disorders under Somatic Symptom Disorders.
Theere is a proposal to subsume Dissociative Fugue under Disssociative Amnesia. Similarly there is a proposal to remove Dissociative Trance Disorder and integrate the criteria into the diagnosis of Dissociative Identity Disorder which has a number of other proposed changes.
Sexual and Gender Identity Disorders
There are a number of new diagnoses.
A new diagnosis of Binge-Eating Disorder is recommended (for further discussion see below). In Anorexia Nervosa there is the proposal to remove the criterion of amenorrhoea whilst in Bulimia Nervosa there are some proposed changes to the frequency of binge eating episodes and the purging criteria.
There are a number of new conditiosns (a number of which subsume other conditions) including Klein-Levin Syndrome, Primary Central Sleep Apnoea, Primary Alveolar Hypoventilation, Rapid Eye Movement Behaviour Disorder and Restless Leg Syndrome amongst others. There are a number of changes to the criteria for narcolepsy including hypocretin deficiency.
There are a large number of suggested changes including the removal of Rett’s Disorder, a number of proposed changes to the Attention Deficit and Hyperactivity Disorder criteria, the inclusion of Post-Traumatic Stress Disorder in school age children and Temper Dysregulation Disorder with Dysphoria which is further discussed below. Interestingly the wording for Separation-Anxiety Disorder may be changed so that it can be used with adults also. This is because there is evidence for an adult separation-anxiety disorder.
Impulse Control Disorders Not Elsewhere Classified
There is a proposal to include Pathological Gambling with substance-related disorders. There are proposed changes for Trichotillomania further discussed below.
There is a proposal to move Adjustment Disorder to a grouping of Trauma and Stress-Related Conditions.
Discussion of the Draft DSM-V Changes Elsewhere in the Media
Links to some of the discussions elsewhere in the media are given below.
General
The Time article looks at a number of proposed changes for DSM-V which includes the criteria for making a diagnosis of depression,use of a continuum and the case for autistic spectrum disorders, the possible grouping of non-dependence inducing substances together with dependence inducing substances in the addiction and related disorders, reducing the number of personality disorder types and making some amendments to some of the sexual disorders. Over at PsychCentral, Dr Grohol looks at a number of features of the DSM-V draft. He is encouraging of the inclusion of Binge Eating Disorder, but is critical of the criteria used in minor neurocognitive disorder, behavioural addictions and also temper dysregulation disorder whcih has a narrow time period fo 6 to 10 years for diagnosis. Over at the ‘Psyche Brown Bag‘ blog, Joyce Anestis comments on the restructuring of the multiaxial system as well as the arrival of a number of new disorders including ‘hoarding disorder’, ‘olfactory reference syndrome’, ‘skin picking disorder’ and ‘psychosis risk syndrome’ amongst others and is also confused by the proposed changes to the personality disorders. The Times has a look at a number of the proposed changes including ‘sluggish cognitive tempo disorder’. Web MD has an article on the changes and features an interview with Dr First who is critical of the utility of the diagnosis of ‘Psychotic Risk Syndrome’.
Dr Dan Carlat has a discussion of the proposed criteria on his blog and seems fairly positive on these (however I would just add that there are neurobiological criteria for a number of disorders in DSM-IV/DSM-V draft e.g hypocretin deficiency in narcolepsy above). He notes that temper dysregulation disorder is being favoured as it would avoid a diagnosis of bipolar disorder in children in a number of cases. He’s in favour the use of addiction in place of dependence or abuse and also the use of the concept of binge-eating disorder. The New York Times has a piece featuring interviews with several psychiatrists and 230 comments at the time of writing. Integral Options cafe has links to a number of posts including those on the NPR site. An article at the NPR website examines the limits of the checklist approach and how severity might be measured when using a dimensional approach. The Economist has a piece on the history of the diagnostic criteria but also cover some of the disputes that have taken place. ‘DSM-V and ICD-11 watch’ have some interesting links as well as a brief look at suggestions for medically unexplained symptoms. Dr Finnerty has an overview of proposed changes as well as some useful links. Mind Hacks has coverage here and here. The APA have a facebook site that interested readers can join.
‘Addictions’
Stanton Peele covers the proposed use of the term addictions in this ‘The Huffington Post’ article. The ‘Join Together‘ website features an interview with Dr Charles O’Brien who is chair of the APA’s DSM substances related disorders workgroup. He explains the distinction between dependence and addiction and the consideration of including the term addiction in DSM-V. They also discuss the possibility of collecting behavioural addictions together with alcohol and other drug related disorders.
Anxiety Disorders and OCD
Tom Corboy director of the ‘OCD Center of Los Angeles’ writes about a number of proposed changes over at the ‘OCD Center of Los Angeles’ blog. Thus Corboy discusses the suggested use of an ‘Anxiety and Obsessive Compulsive Disorder Spectrum’. Corboy is also critical of the suggestion of agaraphobia without panic disorder, in favour of moving Body Dysmorphic Disorder into the ‘Anxiety and Obsessive Compulsive Disorder Spectrum’ and adding a muscle dysmorphia variant, critical of the aggregation of 4 somatoform disorders including hypochondriasis, in favour of the relabelling of trichotillomania as ‘hair pulling disorder’ and also for the inclusion of skin picking disorder.
Intellectual Disability
Over at the blog ‘Mental Incompetence and the Death Penalty‘ there is a guest post by Dr Watson. He criticises the proposed criteria for intellectual disability on the basis that there doesnt appear to be a consideration of the standard error for IQ testing meaning that there is what he describes as a ‘bright light’ cut-off point of 70 or below whereas in practice there is a group that are scored over 70 who would still be included amongst a number of criticisms.
Bipolar Disorder in Children
Over at the NPR website, there is a wider discussion of the diagnosis of bipolar disorder in children as well as the more recent ‘temper dysregulation disorder’.
Autistic Spectrum Disorders
The Left-Brain Right-Brain blog compares the criteria in DSM-IV with those in DSM-V for autistic disorder and autistic spectrum disorders respectively and links to a number of other articles on the subject. There is another discussion of the autistic spectrum disorders proposition here. There is further coverage here and here.
Eating Disorders
Time has a piece on orthorexia which hasn’t made it into the draft version of DSM-V. There is also coverage of the proposed changes at the Ed-Bites blog (with 15 comments at the time of writing).
Dr Dan Carlat takes a further look at the DSM-V draft proposals here. Dr Charles Parker has further coverage here and also over at the Corpus Callosum blog. There is a look at grief in the draft DSM-V proposals at Psychotherapy Brown Bag.
Evolutionary Psychiatry/Human Evolution/Origins of Civilisation/Cultural History
In an podcast/article at the Guardian there is a look at a new book looking at the inner lives of animals. There is a brief description of tree snagging – the tendency of orang-utans to jump from a falling tree at the last moment which has been likened to ‘thrill-seeking’. Colin Blakemore argues in this piece that the human brain increased in volume dramatically as a result of a new mutation at around the time of mitochondrial Eve 200,000 years ago rather than through gradual cumulative culture-associated changes. In another proposal Professor Bruce Yankner speculates that an increase in energy utilisation by the human brain could explain why humans are susceptible to Alzheimer’s Disease which is not identified in other species (even those with large brains). While not directly related to mental illness but instead to models of human evolution, the Laetoli footprints have been analysed and in this paper the authors state that they are the earliest evidence of hominid bipedalism (3.6 million years ago). There are theories that suggest that bipedalism was accompanied by adaptive cognitive changes. There is an interesting piece on cultural transmission in chimpanzees at the primate diaries here. Determining ape evolution from environmental clues secondary to antelope teeth wear patterns 8 million years ago. 58,000 year old glue and colour production in Southern Africa is discussed here. Fossil evidence suggests that fish and crocodiles feature in diet of Homo Erectus ancestors. The earliest British Neanderthal artefacts dated to 100,00 years ago although controversial but later being predated by an Essex finding.
Historian’s analysis suggests Plato used musical code to signify important parts of his text http://bit.ly/95io47. Mitochondrial analysis and the peopling of North America is discussed here http://bit.ly/97Wm8M. Computer deciphers ancient language in a few hours http://bit.ly/aL81Wy. There is evidence that multicellular life began 2.1 billion years ago http://bit.ly/cU6wzt. Fast adaptation to the environment in Tibetans provoked a lot of media interest and is covered here http://bit.ly/9ZlGAK. There is a Discovery piece on Neanderthal teeth dating study http://bit.ly/apkTeW. Music has a strong relationship to language and recent research covered here highlights the close relationship between the two. This relationship has a number of possible implications in a wide number of areas which involve language. A recent study (from a few months back) looked at music appreciation in cotton-top tamarins (a form of New World monkey) and the researchers found that they were responsive to music written specifically for them but not to human music. The music can be heard at the link above and was based on the tamarin’s own calls and other vocalisations. For anyone curious about what cotton-top tamarins look like, I’ve made two short videos (here and here). One of the factors that influences evolution is culture. There is a subtle but intriguing insight into a phenomenon which influences environmental pressures. In this article on Primatology.Net, there is a look at how cultural practices influence the interactions between humans and local macaques in Sulawi Sulawesi.
There was a study at Twycross zoo showing evidence that Orang-Utan gestures may signal intention http://bit.ly/dBpoMi. The discovery of a 3.6 my old A Afarensis partial skeleton produced a lot of discussion http://bit.ly/bSgmdI. A computer simulation and teeth analysis suggest Neanderthal/human divergence 1/2 million years earlier http://bit.ly/dk7elI. Orang utan learning to swim is covered here http://bit.ly/aNbYp5. Chimpanzees engage in territorial warfare http://bit.ly/bwcf04. A possible new hominin species has been discovered and the findings reported in the journal Nature. A finger bone was found in Siberia and an analysis of the mitochondrial DNA was undertaken. There is a suggestion that this species would have lived 30,000 years ago and could have coexisted with humans, neanderthals and Homo Floresiensi. There is detailed coverage in this article and a critical perspective is given here. If the above is confirmed by further analysis then it has been suggested that there were multiple waves of migration out of Africa rather than the two classically described. The relationship to mental illness is more tenuous as these findings are relevant to generic models of human evolution e.g adaptation to cohabitation with a competing hominin species which in turn can be used to interpret illness. A finding of general interest for human evolution is the skeleton of a child in a cave in South Africa which has been named as a new species – Australopithecus Sediba and is estimated to have lived between 1.78 to 1.95 million years ago . Although there is suggestion that this species may be intermediate between Austrolopithecus and Homo Sapiens, critics have argued that further work remains to be done to examine a number of standard morphological features before conclusions can be drawn.
In a widely reported study (see here, here and here) presented at the American Association of Physical Anthropologists, researchers looked at regions of DNA in the genomes of 1983 people from Europe, Asia, Africa, the Americas and Oceania. These regions are known as microsatellite regions and vary between populations. By looking at the degree of variation, the researchers were able to produce a corresponding evolutionary timeline factoring in variables such as estimated mutation rates. The researchers predicted two time periods during which interbreeding with another species was necessary to account for their findings. These periods were 55,000 years ago for the Eastern Mediterranean and 45,000 years ago for Eastern Asia. The candidates for interbreeding include Homo Neanderthalensis and Homo Floresiensis. Such interbreeding could potentially explain the recent finding of a possibly previously unknown hominin – Denisova hominin – found in Siberia. The estimated periods of interbreeding also correspond approximately to the finding of pigmentation on clam-shells in Spain which are thought to have been used as body paint by Neanderthals. Needless to say if these findings are confirmed by a soon-to-be complete analysis of the Neanderthal genome then they would have wide ranging implications. The period of approximately 60,000 years ago corresponds to the lower limit of a hypothesised bottleneck of human evolution in which the human population may have been on the verge of extinction with only a few thousand members although this is a controversial hypothesis.
Team undertaking 3-d analysis of 1.5 million year old footprints probably Homo Erectus. A 2nd 4000 year old figurine from the Orkneys was discovered while 200,000 year old stone ‘knives’ were found in Israel. An extinct but interesting monkey species found in underwater carribean dive. A Wooden henge near stonehenge was a big discovery. A new theory of human evolution involving caring relationship for other species is discussed here. Google funds a 1 year project to open out ancient texts online. There is more on an important fossil primate find here http://bit.ly/9dc1tK. Gorillas playing tag? http://bit.ly/cSEn5c. There has been a lot of media coverage of the recent finding of stone tools suggesting that a human ancestor was present in Norfolk approximately 800,000 years ago. This raises all sorts of questions. For instance, if the environment was similar to present day Scandinavia then how would they survive without clothing? If they did use clothing that would be fairly significant as this is nearly 1 million years ago and would force a reappraisal of milestones in development of human intelligence. There is a video interview with the archaeologists here http://bit.ly/dC3IOg. John Hawks looks at the recent suggestion that the Neanderthal had very powerful musculature and challenges some of the assumptions about hormones by referring to the recently sequenced Neanderthal genome. At the Primatology blog there is a great article on whether animals keep pets. There is a discussion of a paper on personality in non-human primates here. Was Leonardo Da Vinci the pioneer of palaentology? http://bit.ly/d1jPjC … no – he was preceded by Mayans by 1000 years! http://bit.ly/bSvtH8.
A reinterpretation of Mesoamerican civilisation is being brought about by the finding that while Mesoamericans were producing rubber 3600 years ago they had developed further chemical processes to refine the rubber at this time. They used the rubber in shoes among other applications. There is also an ongoing debate about Ardi (13) – the ‘find of the century’ – around the issue of whether he was more man than ape and whether he was living in woodland or savannah. There is good coverage here. One of the current questions in recent evolution is whether Neanderthals contributed to the human gene pool which would have many implications. A recent radiocarbon dating of a site in Portugal revises the date of the last Neanderthal remains to 37,000 years ago. This is significant in terms of the evaluation of a 30,000 year-old child’s skeleton which has properties of both Neanderthals and humans. In a recent study, Chimpanzees and Bonobos were compared on food tasks. The Chimpanzee infants performed differently to the Bonobos on tasks which involved identifying where food was located. The Bonobos were described as delayed in development relative to the Chimpanzees. Chimpanzees are more closely related to humans than Bonobos as Chimpanzees and Bonobos diverged some 1.3 million years ago. Slightly off-topic but the remains of a 7000-year old amputee in France shows evidence of surgical amputation without subsequent infection.
A structural imaging study published in Nature Neuroscience replicated findings in other primates – that the size of the Amygdala correlated with the number of people in a person’s social network. So now we have some convincing evidence that the Amygdala is playing an important role in social networking and it will be interesting to see how models of social functioning incorporate these findings. Chimpanzees in the wild have been observed carrying around sticks until they have offspring. The researchers inferred that they were treating the sticks as a human child would treat a doll and then argued that gender specific roles have a strong evolutionary basis. Shopping is reframed as foraging in evolutionary terms and discussed in this article. Australian aboriginal cave artwork has been found to contain living material in the form of fungus and bacteria and it is thought that this would have replaced the original pigmentation and would account for the difficulties in dating the artwork.
An interesting finding has been the interpretation of a 50,000 year-old Neanderthal clam shall which contains remnants of yellow and red pigmentation together with a black mineral substance. The researchers have concluded that this pigmentation was being used as make-up. Since humans did not arrive in Europe till much later, it was concluded that this is evidence of a Neanderthal culture and this adds to other evidence about Neanderthal intelligence (see here also). This also raises possible questions about the transformation of human art on entering Europe. The most interesting question however is whether Neanderthals are part of our genetic heritage and that question will hopefully be answered with the sequencing of specimens of the Neanderthal genome. The recent sequencing of the Chimpanzee y chromosome suggests that chimpanzees have between one-third and one-half of the genes in the human genome and that the y chromsome has undergone rapid changes relative to the other chromosomes which have been sequenced in both humans and chimpanzees. This should have implications for the kind of inferences we can draw.
While not directly related to humans, this news article involves an interview with a researcher and looks at the ‘evolution’ of stray dogs in russia. The dogs have to adapt to urban conditions. It does raise the question of how much urbanisation impacts on evolution although the selective pressures on dogs will be significantly different from people in these environments (it was interesting to see that the dogs have learnt to ride on the underground!). A mathematical model has been constructed to investigate the coevolution of the hands and feet in humans basing some of the assumptions on measurements in the humans and chimpanzees. The model supports the hypothesis that changes in the feet could affect the shape of the hands (and vice versa) and is interesting in view of the recent publication of the Ardi find (the authors of the Ardi publications took 17 years to prepare the material before publication!) a distant human ancestor which moved through the trees as well as walking upright.
There is an interesting write-up on a recent hypothesis by Professor Wheeler that cooking food may have led to an increase in brain size. The essence of the argument is that cooking reduces the amount of energy needed to digest food. In moving from Austrolopithecus to Homo Erectus and Homo Habilis there was a reduction in the size of the intestines and an increase in brain volume. The argument is that these anatomical changes were causally related to corresponding behavioural changes which enabled a significantly higher proportion of the body’s resources (i.e energy) to be allocated to the brain. Indeed this has been the subject of a Horizon programme which is available for a limited time here. There’s another interesting write-up, this time of a conference examining the ‘Origins of Human Uniqueness and Behavioural Modernity’. Discussion took place around a number of subjects including the possible role of gifts and adornements particularly in the role of signalling social status. The Primatology blog has a look at a recent study on the length of Macaque ‘conversations’.
Johan Lehrer has written a piece on evolutionary psychiatry – ‘The Upside of Depression‘ (the full article is in the New York Times here) and which has produced a lot of debate. In the article, Lehrer explains the analytic-rumination theory which suggests that depression may have an adaptive advantage associated with improved performance on ‘intelligence tests’. However there are a number of difficulties with this. For instance with depression, clinicians can see a deterioration in cognitive performance and problems with memory and concentration are two of the diagnostic criteria for depression. Here is one study for instance that shows significant impairment on cognitive tasks in people with depression compared to a control group. There are other complications however. For instance depression can manifest differently and has multiple aetiologies meaning that it is a heterogenous disorder. As such, any successful theory is likely to explain only a proportion of cases. Clinical depression as distinct from normal sadness is associated with impairment in a number of domains and can be associated with considerable distress. On the one hand, it is encouraging that a model for depression is being discussed in a wider forum as models of illness are extremely important in generating an understanding and moving towards improved treatments. Indeed the interest raised has moved the discussion of this model forwards very quickly. On the other hand any discussion should be tackled sensitively as there are many people with depression (and their families) who have experienced significant suffering as a result of their illness. The key to this debate is in understanding that it is several steps removed from decisions about treatment. If there are any conclusions that would influence treatment then the relevant studies would need to be undertaken in order to move from speculation to evidence-based decision making. The debate has moved forwards with several people responding. For instance Dr Ronald Pies responds here and here, with Lehrer responding here. There is also another perspective over at neuron culture here.
2011
There were many interesting developments in 2011. The world population reached 7 billion although this is an estimate in the absence of a global census. A population of this size brings with it many challenges but technology (particularly social media) brings the world’s population closer together. For me one of the most remarkable studies was the functional Magnetic Resonance Imaging study of Gallant and colleagues. By gathering an extraordinary amount of data and using a very smart approach to the analysis of this data they were able to correlate the activity recorded in the visual part of the brain (occipital cortex) with what was being seen by the person and indeed to predict this with astonishing accuracy. Two illustrative videos from this study are to be found below. However Rene Descartes, the 16th Century French philosopher may have the last word here as it still doesn’t answer the thorny question of where the experience of seeing is being experienced – although things have moved on and our conception of dualism is more concerned with the language of mind and brain rather than a distinction between mind and body. Various brain related technologies or new applications of established technologies have been developed including a method to improve learning through the application of electrical currents which is in the very early stages of development (demonstrated at the British Science Festival), functional Electrical Impedance Tomography by Evoked Response to investigate consciousness in people undergoing anaesthesia, an early trial of Transcranial Magnetic Stimulation in the management of post-CVA dysphagia, EEG/fMRI combinations to investigate lucid dreaming and brain reading – the use of artificial intelligence to analyse brain imaging data as well as Deep Brain Stimulation associated with neurogenesis in the Hippocampus. Much of this work is in the early stages and the efficacy of such approaches will be established in due course. The House of Commons Science and Technology Committee Report makes recommendations for the process of publishing in scientific journals following a number of recent controversies in this area.
Professor Simon Baron-Cohen presents an important hypothesis in his book ‘Zero Degrees of Empathy’ in which he reframes Personality Disorders as disorders of empathy. Given the practical utility of such a framework this would benefit from a wide and prolonged debate. Genetics is advancing at a phenomenal pace – an obvious example being the field of personal Genomics where you can send off a sample of genetic material to a Genomics company for sequencing and receive detailed information about your genetic make-up. A recent genetics study looked at gene expression in the Prefrontal Cortex and after using over a trillion pieces of data, the researchers concluded that there was more variation in gene expression in the same person over their lifespan than between people. There was also evidence of the role of epigenetics in longevity – non-DNA factors that contribute to gene expression – in one species where the methylation of DNA was found to contribute to 30% of the variation in longevity. While advances in technology are remarkable there is a lot of research which suggests that lifestyle also plays an important role in the health of the brain. On the theme of lifestyle, the Royal College of Psychiatrists also published a report on substance misuse in older adults. Prime Minister David Cameron’s Health and Social Care Bill is passing through the House of Lords currently (a line-by-line reading is due to be scheduled) and when implemented will mean a number of significant changes in UK healthcare. This is also taking place in the context of a wider ‘Big Society’ implementation which was reflected in the New Year’s honours list.
In relation to mood disorders, one longitudinal study lasting several decades and being moderately sized provided good evidence that antidepressants are associated with a reduction in suicide. Another study found that acetylation of DNA histones was associated with some cases of Schizophrenia thus adding to the number of associated conditions that can be included in the differential diagnosis while another study provided evidence of an increased number of de novo mutations in 40 genes compared to unaffected relatives. Thanks to new developments in genetics there has been a recently characterised condition known as Hereditary Diffuse Leucoencepalopathy with Spheroids (HDLS) which one group thinks will be increasingly recognised with increasing availability of diagnostic testing. Schmidt and colleagues published their initial findings on different rates of progression of Alzheimer’s Disease and it will be interesting to see further work in this area. The World Alzheimer’s Report 2011 concludes a concerning figure of roughly 36 million people around the world who are estimated to have Alzheimer’s Disease but have not yet received a diagnosis. Normal Pressure Hydrocephalus can be associated with cognitive impairment but shunting doesn’t always reverse the cognitive impairment. In one small study the researchers provided evidence that this may result from comorbidity in those cases.
Genetic data has helped to answer questions about human migration patterns. Recent analysis concluded that Australian Aborigines are the first humans to have left Africa some 62 to 75,000 years ago followed some 50,000 years later by a second wave of migration. What is even more remarkable is that a new group of ancient hominids have been discovered and are known to have contributed to modern human populations. They are known as the Denisovan’s and are known from DNA analysis of a finger bone in a Siberian Cave. They diverged from our family tree some 300,000 years ago but after this period of separation contributed to the modern human gene pool. Little is known about them except that at 30,000 years ago they were using necklaces suggesting some degree of sophistication and that they also interbred with Neanderthals. Thus an important part of our historical narrative is being filled in by genetics and archaeology which has otherwise been lost from oral or written traditions.
Miscellaneous
Congratulations to Professor Sue Bailey who was appointed as President of the Royal College of Psychiatrists and to the outgoing President Professor Dinesh Bhugra who has become president elect of the World Psychiatric Association. A study in the Journal of European Neuropsychopharmacology provides evidence that psychiatric illness is the leading cause of illness in Europe. There is an interesting editorial in the October edition of the British Journal of Psychiatry by Harrison and colleagues (Harrison et al, 2011) the premise being that psychopharmacology should take on a more central role within the profession. It will be interesting to see if and how this debate develops particularly in terms of modelling the practical implications and implementation according to context. The BMA have brought out new guidelines on protecting vulnerable adults. There is a write-up of a study comparing 23,199 people who experienced traumatic brain injury and received care in hospital with 69,597 people without traumatic brain-injury who received care in hospital. The researchers found that within 3 months of the injury, the traumatic brain injury group had a 10-fold higher prevalence of stroke than the non-traumatic brain injury group with just under 1 in every 33 people being affected. This increased risk decreased with time but at 5 years was 2.3 x higher than the non-traumatic brain injury group. The researchers also found that a number of characteristics of the brain injury including fracture of the skull modified risk.
In a study published in ‘The Psychiatrist’ (Perecherla et al, 2011), a research team looked at a person’s understanding of their medication in a group of older adult inpatients on a psychiatry ward (n=86). They thought that people might have a better understanding of the medication for their medical illnesses rather than the mental illnesses. However they found that people had a roughly equivalent understanding of the drugs for their medical and mental illnesses. Although they used a screening tool to exclude those with cognitive impairment, this still appeared to play a role in a person’s understanding of their medication in some of the people. There is an interesting article on Medically Unexplained Symptoms illustrated with cases and diagnostic algorithms available here.
In a remarkable study researchers have been able to intrepret the activity in people’s visual cortex and correlated this with video images. These results are a convincing demonstration of the validity of functional Magnetic Resonance Imaging (although there are various nuances in the interpretation of the results). To get to these results the researchers used large datasets and long training periods for the subjects which consisted of the researchers themselves. Firstly the researchers needed to correlate activity in multiple areas of the visual cortex with large numbers of video segments. For this the subjects had to watch a lot of video clips whilst being scanned to build up the library of video clip-activity pairs. The researchers developed an understanding of the relationship of perception of different line orientations and other basic visual information to brain activity. Then the researchers’ program scanned through 18 million seconds of video footage from YouTube generating likely brain activity correlates. Then the subjects watched a new set of previously unseen clips and the software translated the brain activity into the nearest matches from the 18 million second sample set. The end results are the blurry images seen below.
The researchers however could sharpen up the videos by refining the program. There are many obvious questions to ask here. For instance when we use imagination one hypothesis states that imagination utilises the visual cortex rather than higher association areas. The researchers would be able to investigate this by asking subjects to imagine a scene whilst recording brain activity before translating this. These results would also be incredibly important for researchers investigating the causes of visual hallucinations in people with Schizophrenia and Dementia.
A research group have presented their findings at the British Science Festival. They have used an electric stimulating device to apply a small electrical current to the motor cortex in order to improve learning on a motor task. It will be interesting to see further details on the research when they are published. There has been a recent study looking at response to social stress. The study was modestly sized (32 participants) and the researchers used fMRI to analyse brain activity in response to social stressors. They found that people in urban areas responded differently to those in rural areas. Participants in urban areas were more likely to activate the Amygdala and those in rural areas were more likely to activate the Cingulate Cortex in response to the social stressors presented in the study paradigm. The results are discussed in the context of other researhc which shows a higher prevalence of Schizophrenia in urban areas and the suggestion from this study at least is that growing up in an urban area may lead to a difference in the way the brain responds to stressful situations. However it must be said that this a small study and this hypothesis needs rigorous testing. Researchers have used a technique known as ‘Functional Electrical Impedance Tomography by Evoked Response’ fEITER to investigate ‘consciousness’ in people undergoing anaesthesia. Crudely speaking, as the consciousness levels were found to decrease there were corresponding changes in actvitiy in defined anatomical regions. Although this preliminary report is a little vague, the research team are still analysing the data but the combination of the effectiveness of the new technology and the correlation of activity with levels of consciousness will be very exciting results if this holds up to further analysis. There is a write-up of an interesting study relating GABA levels in the brain to ability to learn motor tasks. GABA levels in the brain were measured using a technique referred to as Magnetic Resonance Spectroscopy. The researchers were able to use a standardised test which involved the application of a direct current to subjects’ scalps. This is known to produce a change in GABA levels. The magnitude of the change in subjects was found to positively correlate with the rate at which subjects learnt on motor tasks. It will be interesting to see further research in this area. A review of two decades of functional Magnetic Resonance Imaging studies has been completed by the Wellcome Trust and they conclude that there is still much work to be done in translating findings into the clinical arena (see here). In a potentially very important study, researchers have identified evidence that Magnetic Resonance Imaging scanners may have an effect on the fluid in the inner ear canals causing subjects to experience nystagmus and symptoms such as vertigo. The researchers also suggest that this could interfere with the results of fMRI studies. The researchers methods were quite ingenious. They conducted the study in the dark but used night cameras to monitor the subjects eyes for nystagmus. They also involved two subjects with labyrinthine disorders. These two subjects did not experience nystagmus whilst other subjects did. No doubt this study will receive close interest from the neuroimaging community.
There is evidence that Deep Brain Stimulation may be associated with neurogenesis in the Hippocampus. There is a write-up of one study which provides preliminary evidence of a benefit from Transcranial Magnetic Stimulation in post-stroke dysphagia. This was a small trial and it will be interesting to see the results of further studies in this area. Researchers used EEG and fMRI to investigate lucid dreamers. The lucid dreamers were scanned whilst asleep and signalled that they were dreaming of clenching their fists by moving their eyes horizontally several times. Only two episodes were captured but they displayed similar activity to hand clenching. However these results should be viewed with caution as only two episodes were captured and it will be interesting to see the results of replication studies. ‘Brain reading’ which is a combination of using neuroimaging data and making predictions based on analysis using artificial intelligence software is discussed in this article in relation to recent research into alcohol use and craving. In a freely available paper researchers used fMRI to investigate imaging of future events (via MariaPage). They found evidence that when subjects had successfully recalled their imagined future events there was evidence that the right Hippocampus was activated. The researchers suggest that the Hippocampus is used to store the details of these imagined events. This continues the debate on the role of hippocampus in imagining future events. In another study the researchers examined the visual perception of objects. Visual information in the form of parts of a car were presented to the subjects with a number of transformations making it more difficult to identify the moving objects. In order to process the visual information the researchers suggested on the basis of their evidence that the visual information was being grouped and that the subjects were processing the data at a rate of about 10 groups per second. Furthermore the groups were being processed one at a time. If this is replicated then it means that when we perceive visual motion – for instance a group of cars driving down the road we would be processing them not as a group of cars moving but a sequential processing of individual cars. However the brain may have additional techniques for processing ‘natural’ visual information in contrast with the abstract information presented in this experiment. Researchers examining the auditory processing areas in the cerebral cortex in humans have better characterised the processing activities. Much like the processing of vision, the processing of sound involves ‘what’ and ‘where’ streams. The researchers in the study reported on here have investigated the ‘what’ stream and identified three components which analyse basic tones, multiple tones and speech sounds such as vowels. This better understanding will be useful into a number of illnesses in which speech is affected. Dr Shock has a piece on Deep Brain Stimulation in Alzheimer’s Disease here.
There is a very interesting article on culturomics in the journal Nature. Aiden a researcher is looking into analysing the content of culture through the textual analysis of books. He’s collaborated with Google who released a tool called the ‘Google Ngram Viewer’. Essentially the tool enables people to search all the books Google has digitised. The article discusses some of the controversies in this emerging field of the digital humanities. Playing about with the Ngram Viewer tool I got some interesting results. Here’s one for psychiatry
This is showing a peak of the term ‘psychiatry’ in books in the late 1970 followed by a consistent decline. However there has to be some caution in interpreting the results. For instance we need to ensure there is no selection bias in the books that have been digitised and to know what percentage of the books published at that time are included in the analysis. Also are there any statistical comparisons between the years which would help to interpret apparent visual trends that are generated? Still if there is a large enough sample of books it does present an interesting proxy to culture and can be used to frame further investigation. For instance books can be sampled to confirm the results. If the results above are valid then we can ask what was happening in the late 1970′s in psychiatry? Also why has there been a decline subsequently? Perhaps the ascent in the 1940′s and 1950′s was associated with the advent of treatments including ECT, antipsychotics and antidepressants. Here are some other interesting results.
For psychosis there is a decline in more recent times (although the same is not true for the term schizophrenia).
For Autism there is a marked increase in the use of the term in more recent times.
For PTSD there is an increase with a slight dip at the end of the graph.
For Dementia there has been a large increase in the use of the term in the digitised books. The tool is a easy to use and opens up many possibilities in exploring cultural phenomenon including the wider discussion of illnesses and their treatments.
The connections betweeen groups of neurons are extremely complex with large numbers of synapses. Studying these networks has been accelerated through the development of microscopy techniques as well as software programs. A group in Germany have used a program called KNOSSOS in conjunction with a collaborative approach between researchers to characterise a network of 100 neurons and there is a write-up here. Professor Sheng Ding in colloboration with Professor Stuart Lipton at the University of California San Francisco (USCF) has transformed human skin cells into neurons which will have many potential applications. The team took skin cells from a 55 year old lady and converted them to neurons using a combination of genes and microRNA. In another development the cost of personal genomics has come down with one company offering 80 x coverage (meaning that the genome is covered 80 times to reduce the risk of errors). It will be interesting to see how this will be linked in with mainstream health services. Meanwhile a new centre for neuroscience is being built at University College London. There is a brief write-up here on how cognitive biases can influence judgement in science. There is also a brief but interesting write-up of the science of team training here. Recent research suggests that when people are presented with weak evidence to support an argument that this is less persuasive than having no evidence at all (via MariaPage). A recent study suggests that near-death experiences are associated with serotonin. There is a write-up of a study in C.Elegans worms which looks at heritability of longevity. The researchers found that the methylation of DNA in the worms accounted for up to 30% of the variation in longevity. They argue that this is a non-DNA form of heritability. If these findings were generalised to humans it would mean that in studies of aging, researchers would need to look for patterns of methylation of DNA and not just for longevity genes in order to gain a better understanding of aging.
Ben Goldacre has an interesting article on apparent flaws in neuroscience research. Goldacre looks at a paper by Niewenhuis and colleagues where they examine 513 papers and identify a systematic error in statistical analysis. Essentially positive findings in response to interventions are reported without comparison with the control group. The approach by the authors is somewhat reminiscent of the Vul et al paper on Neuroimaging research (see here) in the sense that both approaches can be considered as meta-research. In light of the controversial surrounding the MMR Vaccine a report by the House of Commons Science and Technology Committee included a number of recommendations that may be helpful in challenging the difficulties reported by Niewenhuis and colleagues. There is also a need for an international response to fully address the issues. There have been some interesting recommendations by the House of Commons Science and Technology Committee Report (see also coverage here). The MP’s make recommendations including training of scientists undertaking the peer review as well as increased transparency, availability of the data online and use of pre-print servers to improve the peer review process. These recommendations were made in light of controversies such as those surrounding the MMR Vaccine. Interestingly the pre-print server model was very instructive in an academic debate in neuroimaging.
In a longitudinal study (the three-cities study) looking at the use of the Mediterranean Diet researchers found that women with the highest adherence to the Mediterranean diet had a 50% risk reduction in incident disability (evaluated using two measures of functioning) relative to the group with lowest adherence. Previous research supports a beneficial effect of the Mediterranean Diet as in a BMJ Meta-analysis (freely available here)(see also discussion on this blog here, here, here and here). There is interesting coverage of a recent study suggesting that components in the blood influence neurogenesis in the central nervous system in an age-dependent manner. An intuitive finding but one which is useful to know nevertheless is that planning meals can be both economical and lead to healthier eating as the researchers in this study found.
In a story that has provoked a widespread response in the Anthropology community a US politician has suggested that there isn’t a need for more Anthropology students at University in Florida. Within the statement he comments on anthropology not being a science and implies that it doesn’t lead to good job prospects. There are some similarities between anthropology and psychiatry in that both are fields which involve the overlap of science and the humanities. Indeed Anthropology celebrates and brings an invaluable understanding of the diversity of humanity and so a criticism of Anthropology becomes a criticism of the need to understand this diversity. Anthropologists have also made significant contributions to a variety of fields and it is at times such as this when the profession answers its critics that the significance of this field can be better appreciated and is also a time at which the profession strengthens its identity. The American Anthropological Association has responded with a statement. There is also an interesting podcast interview here. However the truly inspiring response is this one which details the work of anthropologists in Florida and the impact that this is having. There are lessons about these responses that can be transferred to psychiatry. The Blog Linguistic Anthropology has a round-up of not-for-profit anthropology journals here.
On the theme of Anthropology, ethnographer Sarah Pinto writes a very interesting article on the study of patient’s movements in psychiatric wards at the anthropology website Somatosphere (via VaughanBell). Somatosphere also have a round-up of 2011 here. In a post-mortem study in which researchers used 49000 gene probes in 269 brains across the lifespan, researchers obtained over a trillion pieces of information and found evidence that the expression of genes in the prefrontal cortex peaks just after birth. Following this a number of genes switch off and reduce towards middle age. In older adults the genes are increasingly expressed. The write-up covers a number of other studies with complex but very interesting results. In one study using 1.4 million probes to examine 57 human brains, the researchers found evidence that the brain location and timing influenced gene expression more significantly than individual variation. Accelerometers were used to identify an asymmetric arm swing during gait as an early manifestation of Parkinson’s Disease in this study.
There’s an interesting report on Kevin Healy who is described as having ‘highly superior autobiographical memory’ and who states that he has remembered all the calendar dates since 1752 and that he is able to remember significant dates from his own life. He is asked questions during the interview and is able to give accurate responses. His abilities are reminiscent of those of the famous Russian mnemonist Solomon Shereshevsky who was studied by Alexander Luria and also to Jill Price. There is a write-up here of a study published in the journal Age in which the researchers looked at the performance of sportspeople in a various fields. They found that peformance for swimmers peaked at age 21 and for chess grandmasters at 31. In the November issue of The British Journal of Psychiatry there is a special mention of psychiatrist Dr Henry Rollin who having celebrated his 101st Birthday is continuing to submit papers to journals! There is a short piece on a doctor who is still working at 100 here. An open access journal ‘Longevity and Healthspan‘ has recently started up.
In the November issues there is also a study on the effects of the Nagasaki bombing at the end of the World War II on the mental health of the local population. The researchers looked at people that had been in the area near the blast but without exposure to the radiation compared to a control group who were not in the area of the blast. A key finding was that survivors of the nuclear blast were more likely to suffer mental illness when they were in the vicinity of the blast compared to the control group. This was assessed using the General Health Questionnaire 28 score. Part of this finding could be accounted for by knowledge about nuclear blasts. Thus those who did not understand that a nuclear flash was not associated with radiation injury scored more highly on the GHQ 28 than those who understood that witnessing the flash would not in itself cause radiation injury. This means that not understanding the nature of the nuclear flash had consequences for survivors mental health that appeared to last throughout their lives.
There is an interview with Professor Simon Baron-Cohen on his book ‘The Science of Evil’ here. ‘Zero Degrees of Empathy’ is a new book by Professor Simon Baron-Cohen (see reviews here, here, here, here, here and here). Baron-Cohen presents an important hypothesis in which he reframes several personality disorders as being primarily disorders of empathy. This hypothesis has a number of important implications particularly in terms of how services might relate to people with these personality disorder labels. Given the implications for society this book offers an important step forward in opening up a wider debate on how society might reframe this relationship. However Baron-Cohen also looks at the concept of evil and gives examples whilst suggesting that this concept can also be understood in terms of empathy. However this is slightly more complicated and several of the reviewers above have focused on these arguments rather than the personality disorder issues. With the preparation for DSM-V there may be a case for a more pressing discussion of the reinterpretation of personality disorders such as narcissistic, borderline and antisocial personality disorder in the relevant forums.
There are some interesting results from a study in elementary schools in Hawaii where the researchers have provided evidence of a benefit from adding ‘character building’ to the curriculum. This was associated with reduced suspensions and absenteeism among other findings. There is an interesting reappraisal of the diagnosis of Dangerous and Severe Personality Disorder by Dr Duggan in the British Journal of Psychiatry. He argues that there have been both advantages and disadvantages to the programme which have included additional funding and research in this area although there have been difficulties in using the diagnostic criteria as prognostic indicators. Duggan also writes that there is a move to ‘phase out’ the DPSD programme.
The recent riots starting in Tottenham, London and extending to other parts of England is likely to have impacted on Mental Health Act assessments amongst the many other serious consequences. There have been a number of commentaries on the riots. In this article by Natalie Wolchover there is a discussion of crowd behaviour in terms of the Elaborated Social Identity Model. The Research Digest has links to a number of articles commenting on the riots from a psychological or neuroscience perspective. There is also this article in Psychology Today looking at the possible role of Mirror Neurons (see here and here) and empathy. Although the application of theories to speculation about the events can be useful there is also a role for quantitative and qualitative research to test the hypotheses in the recent events (i.e the conclusions can be data driven).
The United Nations are projecting that by October 2011 the world will reach a population of 7 billion. Previously the 2010 UN estimates varied from projections of between 6.2 billion people and 15.8 billion people by 2100 depending on fertility rates. These figures also reflect changing demographics with an ageing population across the world as life expectancy increases. A paper published in the journal Science shows how education can significantly influence these projections. There is an article at Scientific American on the global population estimate of 7 billion. Although there have been other estimates which suggest it has already happened there has been no Global Census. The author of this article suggests that a new city of 1 million people needs to be built every 5 days to meet the expected population increase over the course of this century. While this is speculation it is interesting to note that there are significant differences between urban and rural areas in the pattern of mental illnesses (e.g see here). Were such demographic shifts to be realised it would have significant implications for the configuration of psychiatric service provision.
Mood Disorders
In a study of 56 people with DSM-IV diagnoses of Major Depressive Disorder with psychotic features, 41% had revised diagnosis within 2 years including Bipolar Disorder. In an American study looking at older adults admitted to hospital and followed up 3 months after discharge the researchers found that at follow-up 81% of those that were depressed had been depressed on admission to hospital. The researchers interpreted this to mean that most of the cases of depression at follow-up represented persistent depression rather than new onset of depression during the course of the admission. In a 27-year longitudinal study (n=757) researchers looked at people who had been diagnosed with a mood disorder (depression, mania or schizoaffective disorder). They examined the association between antidepressant use and suicide attempts or completed suicides using a propensity model which provides an estimate of a treatment effect in this type of study design. The researchers found that the antidepressants were associated with a large reduction in suicide attempts or suicides
‘Quintile-stratified, propensity-adjusted safety analyses using mixed-effects grouped-time survival models indicate that the risk of suicide attempts or suicides was reduced by 20% among participants taking antidepressants (hazard ratio, 0.80; 95% CI, 0.68-0.95; z = -2.54; P = .011)‘
This is a big effect size in a study with a large sample size over a very respectable follow-up period and will surely contribute to the debate in this area. A moderately sized study (n=200) investigated gender differences in presentation of acute mania. The researchers found that there were statistically significant differences between men and women in presentation and that
‘a predominance of anxiety and depressive symptoms was found in women, whereas increased psychomotor activity was prevalent in men‘
In the British Journal of Psychiatry there is an interesting paper looking at the associations between anxiety in older adults and cognition (Butters et al, 2011). The researchers compared 160 people without dementia meeting the DSM-IV criteria for Generalised Anxiety Disorder (GAD) with a control group (n=37) without a history of psychiatric illness. The Hamilton Rating Scales for Depression and Anxiety were used as well as a neuropsychological battery. The researchers found that the GAD group performed significantly worse than the control group (after a step-wise Bonferroni correction) on the letter number sequencing, the D-KEFS sorting test and the RBANS immediate memory and delayed memory tasks. These findings remained after excluding subjects who met criteria for Major Depressive Disorder which was expected to be a significant confounder. Escitalopram was part of the treatment program and Escitalopram use was associated with an improvement in the D-KEFS scores – a measure of executive function. In subjects that experienced a significant improvement in self-reported anxiety (using the Clinical Global Impressions scale) there was a corresponding improvement in RBANS immediate and delayed memory scores. The study has generated some very specific hypotheses for further testing. A moderately sized study (n=234) showed a significant positive correlation between early response to medication in acute mania in the first week and treatment outcome. A large prospective trial (n=660) of combination antidepressants versus monotherapy as a first-line treatment for depression provided evidence during the 7-month follow-up period that the two combination treatments were just as effective as monotherapy in this study. However only two combinations were examined and combination therapy is not usually considered as first-line treatment in various guidelines.
Substance Misuse
The Royal College of Psychiatrists has released a report on substance misuse in older adults. The college report CR 165 is located here and there is an interview with one of the authors of the report Professor Ilana Crome here (reviewed here). The report is detailed and it is difficult to do this justice in a brief summary and so the reader is directed to the link above. However several principles arise from the report. The authors recommend that older adults are screened for substance misuse in primary care using standardised screening tools, that the recommended upper limit for older adults should be reduced (they recommend 11 units a week), that older adults with substance misuse have many unmet needs and benefit from treatment, that binge drinking limits for older adults should be reduced (they recommend 4.5 units as a limit for men and 3 units for women) and that local policies should be developed to facilitate effective management. The authors also have a number of recommendations about training and research including further evaluation of the therapeutic intervention in older adults with substance misuse. There are seven recommendations and components of future strategic direction including an emphasis on multi-agency partnership. There are detailed outlines of therapeutic interventions in the Appendices. What is also interesting is that there are discussion of exemplary service models. One that I found very interesting was the North Southwark team in which it was noted that ‘up to 50% of admission of older people involved a dual diagnosis’ and they go on to note the importance of alcohol misuse in these presentations. In 2002 5% of patients were identified with alcohol misuse and the psychiatrist undertook an MSc in Public Health Medicine. A few years on and with a multidisciplinary community programme to address alcohol misuse the admissions were reduced to 5%.
The report has generated considerable debate in the media (see links below). Indeed spending a little time looking through the comments on two of the sites below, many of the commentators are critical of the report. A number of themes recur in the posts including perceived interference in the lives of older adults, the actions of a perceived ‘nanny state’, anecdotal cases of alcohol consumption in those that reach an advanced age and the association with enjoyment of life. The comments thus provide an ‘audit trail’ for the debate that is happening in society (although there may be a bias in selection in terms of both readerships and those who have commented rather than just read) and this would form a very useful basis for a qualitative analysis. What was striking to me in reading the comments was that the issues that were frequently discussed by the commentators were slightly different to the main emphasis in the report. For instance the report produces important guidance for psychiatrists to help give them the best advice for the patients that they can provide. Such guidance assumes that the patient has a sense of agency – that is that they have a choice on whether to act on the advice rather than being compelled to do so. However many of the comments give an impression of a compulsion to act on this advice and it would be interesting to see where this is coming from. Another point which arises is the understanding of probability or statistical inference. The report cites a large amount of research undertaken in this area which produces statistical results enabling advice to be given in the form of a balance of probabilities. However in many comments there are references to anecdotal reports of alcohol use in those reaching an advanced age – with the implication of the comment being that in those cases the advice was not valid. This though misses the point about the nature of the findings which provide a balance of probabilities. In other words it is more likely than not. Thus in isolated cases there may be counterexamples but as more outcomes are examined the trend will be towards the results seen in the studies i.e it might work for one person but not for 10. This theme about statistics however is common and it would be interesting to see if in this case it relates to a genuine misunderstanding of statistics or an implied risk/benefit calculation that is not explicitly discussed.
NHS Choices gives the lowdown on the report here; Silver Surfer article here; Independent article here; ITN article here; Sky News article here; Daily Mail article here and here (271 comments at the time of writing); Telegraph article here; BBC article here and here. (567 comments at the time of writing); Metro article here; Yorkshire Evening Post article here; Netdoctor article here; Mail on Sunday article here; International Business Times article here; AFP press release here; Herald Scotland article here; Irish Independent article here; NW Evening Mail article here; Visit Bulgaria article here; Ghana Business News article here; Modern Ghana article here; French Tribune article here; De Havilland article here; South Wales Angus article here; Barchester Healthcare article here; The Periscope Post article here; Bournemouth Echo article here; Best Medical Cover article here; Leicester Mercury article here; Bradford Telegraph and Argus article here; Top News United States article here; 4RFV article here; Express article here; Netdoctor article here; Best Medical Cover article here; Just Drinks article here; Candis article here; On Medica article here; Mediplacements article here.
PTSD
One cross-sectional study provided evidence of a positive correlation between hippocampal volume and recovery from PTSD in war veterans although replication of these findings with a longitudinal design is needed. There are articles on PTSD and the Japanese Tsunami here and here. The articles look at the provision of psychotherapists for PTSD and the anticipation that were will be a large increase in demand as a result of the tragic events that occurred recently.
Psychosis
There’s a study in the American Journal of Psychiatry covered at the Schizophrenia Forum here. The reader is directed to the excellent write-up there but essentially this was a 10-year longitudinal follow-up study of 470 people assessed for psychosis at entry into the study. The diagnosis was revised in fifty percent of patients during the course of the study follow-up period. However if the diagnosis was schizophrenia or bipolar disorder these diagnoses tended to be more stable over the follow-up period compared to other diagnoses. Indeed the prevalence of schizophrenia in the cohort increased with time which was interpreted to mean that the symptoms took some time to appear and be recognised. The researchers are intending to extend the study by another decade. Researchers in a large multicentre trial (n=1080) investigated hallucinations in people with schizophrenia and found that there was geographical variation in the presentation of hallucinations. They suggest that this is evidence in support of cultural interactions with psychosis. The authors of a systematic review risk of conversion from Ultra-High risk state for psychosis to actual psychosis looked at 2462 papers and identified 31 which met their inclusion criteria. They concluded that 76% of the people in the high risk category did not convert to psychosis.
There is a write-up at the Schizophrenia Research Forum on some new trial data on approaches to cognitive and negative symptoms in Schizophrenia. The new approaches include the use of alpha-7 nicotinic cholinergic receptor agonists as well as a GABA-phenothiazine compound although the results from Phase III trials will be needed. A short small-sized trial compared risperidone and escitalopram for treatment of psychosis and agitation showed no difference in efficacy although it would be interesting to see the results of a larger longer-term replication study. There is an unusual case report on ‘cough syrup psychosis’ resulting from excessive use of cough syrup. The authors attributed the psychosis to the ingredient dextromethorphan. One group of researchers examined the question of whether weight gain is a correlate of improvement with antipsychotic treatment in people with schizophrenia. They concluded that an increase in BMI accounted for only 3% of the change in PANNS scores and therefore weight gain was not an important correlate. They go on to discuss the therepeutic implications. The BMJ has an article coauthored by Professor Barnes on whether antidepressants improve negative symptoms in Schizophrenia. The authors conclude that the evidence is equivocal and they offer some practical tips on how to deal with the conclusions from the literature. The authors of this paper on antipsychotic associated hyperprolactinaemia call for randomised controlled trials to evaluate these associations and provide clinicians with guidance on managing these side effects.
People developing a first-episode psychosis after misuse of substances were followed up over a 2-year period (Komuravelli et al, 2011). The researchers found that of the 78 people retained in the study, 46 were retained in follow-up in the services and of these 36 (i.e 78%) had been given a diagnosis of psychosis and this is supported by other similar research in this area. Researchers looked at 65 people with ICD-10 diagnoses of schizophrenia and found that that those with OCD symptoms were more likely to manifest subtle difficulties on motor coordination tests than those without OCD symptoms (freely available here). Furthermore scores on the Positive and Negative Symptoms Scale were more likely to correlate with score on the motor coordination tests in the former group.
In a post-mortem study of people who had been diagnosed with Schizophrenia compared to a control group, researchers have found an association with histone acetylation of DNA. In essence this is the mechanism which enables the DNA to be coiled within the nucleus and the inference here is that this coiling and subsequent gene alteration may be affected in some cases of Schizophrenia leading to potentially new avenues for treatment. In Neuroscience Letters one group reports an association between a common FOXP2 gene variant rs2396753 and grey matter volume in people with Schizophrenia compared to a control group. The FOXP2 gene is thought to play an important role in language. In a moderately sized study (n=225) researchers compared the exomes of people with schizophrenia with relatives and a control group and found evidence that schizophrenia was associated with a high proportion of de novo mutations across 40 genes. A twin study at the Institute of Psychiatry involving twins with Bipolar Disorder or Schizophrenia has identified a number of new candidate regions for disease genes. The authors of a recent meta-analysis concluded that there was no significant relationship between common alleles of the DISC1 (Disrupted in Schizophrenia 1) gene and Schizophrenia.
There is a pilot study of Deep Transcranial Magnetic Stimulation for negative and cognitive symptoms in Schizophrenia (n=15) and on the basis of the results the researchers recommend further research in this area. The author of a review of evidence of ECT in Schizophrenia concluded that catatonic symptoms were the most responsive. While the response of catatonic symptoms to ECT is well established the author also identified a hierarchy of symptom responsiveness on the basis of the review. In a small 8-week study people with schizophrenia either played computer games or engaged in high intensity training (HIT) aerobic exercise. The researchers found a significant improvement in physical outcome measures including maximal oxygen uptake but not in PANNS scores. They recommended HIT in rehabilitation programs. Decreased physical activity was significantly correlated with physical health quality of life in one small study comparing people with Schizophrenia with a control group.
Neuropsychiatry
Researchers have investigated resting state activity in people with agenesis of the Corpus Callosum. Agenesis of the Corpus Callosum is a condition in which the fibres connecting the right and left sides of the brain are absent during development. Previously this was investigated by looking at people who had undergone severance of the fibres in the Corpus Callosum for treating intractable epilepsy. Resting state activity is the activity that occurs in the brain when a person is resting and not engaged in any obvious activity – wakeful rest. The brain areas that are active when recorded using functional Magnetic Resonance Imaging form a characteristic network which has been assumed to involve a communication between both hemispheres of the brain. The researchers in this study found patterns of activity similar to those in people with an intact Corpus Callosum and this raises new questions about the nature of the resting state network. There is a case of Wernicke’s Encepalopathy with involvement of the Fornix at the AJNR blog here.
There is a case report of a person who developed Hashimoto’s Encepalopathy. The researchers completed a neuropsychological assessment and after resolution of the encepalopathy found a residual executive impairment. However case studies are useful in generating hypotheses for further replication studies as there is so much variation between people. There is a write-up of a small study (n=32) investigating amateur football players using Diffuse Tensor Imaging (for further details of the abstract presented at the conference see here as well as the researcher Professor Lipton’s page summarising links to other sites). The researchers found a correlation between self-reports of heading a ball over 1000 times a year and evidence of patterns of brain injury similar to that seen in Traumatic Brain Injury. However the researchers advise due caution in interpretation of these results and suggest that further replication is needed. There is a write-up on a recently discovered genetic condition Hereditary Diffuse Leucoencepalopathy with Spheroids (HDLS) which can now be identified using genetic testing rather than post-mortem analysis and the researchers suggest that this condition may be increasingly recognised.
Dementia
In an American study based at the Mayo Clinic, researchers examined the role of an imaging technique known as Proton Magnetic Spectroscopy in identifying the factors influencing the load of Beta-Amyloid peptide which is thought to be central to the degenerative process in Alzheimer’s Disease. They included 311 people who didn’t have any cognitive impairment and used (11)C-Pittsburgh compound B (PiB) Positron Emission Tomography and (1)H Magnetic Resonance Spectroscopy to image one part of the brain – the Posterior Cingulate Gyrus. With the PET imaging the researchers were able to image the Beta-Amyloid load. With the Magnetic Resonance Spectroscopy, the researchers were able to image the levels of choline in the Posterior Cingulate Gyrus. This is used as a measure of turnover of cell membranes. They were also able to image the levels of creatinine which is thought to be relatively stable and useful for comparing with other molecules of interest (such as choline). The ratio of choline to creatinine can therefore be used as a marker of cell death which is useful for investigating neurodegenerative conditions. Similarly the researchers also investigated the ratio of myo-inositol to creatinine which is again useful in the investigation of neurodegenerative conditions. As expected, the researchers found that the Beta-Amyloid load was significantly associated with both the choline/creatinine and myo-inositol/creatinine ratios. However the researchers also found that the choline/creatinine ratio was significantly associated with performance on a number of cognitive tasks including tests of memory independent of the Beta-Amyloid load. The researchers suggested that the relationship between the choline/creatinine ratio and the impaired performance on cognitive tasks resulted from another process independent of the Beta-Amyloid load. In other words they thought that the probable cell death resulted from a process independent of Alzheimer’s Disease – vascular injury for instance. This is an interesting approach and raises a number of questions. For instance does this relationship predict conversion from to Alzheimer’s Disease or Vascular Dementia? What happens to these relationships in the Hippocampus, a brain region with much closer involvement in the degenerative process in Alzheimer’s Disease. What happens when the choline/creatinine ratio is followed up at multiple points to obtain an average value over a time period? It will be interesting to see further research in this area.
A Dutch group has assessed psychosocial intervention for Alzheimer’s Disease guidelines across 12 European countries using a standardised protocol. Amongst their findings the researchers concluded that
‘The UK NICE SCIE guideline had the best methodological quality and included the most recommendations for psychosocial interventions‘
and that across Europe special attention is needed in terms of updating guidelines with evidence and implementing these guidelines in service delivery. In a longitudinal study involving subjects with non-amnestic and amnestic mild cognitive impairment (naMCI and aMCI respectively) (n=106) amongst other results researchers found that there was a decline in simple attention in both groups but a decline in divided attention in the aMCI group. The researchers suggest further research to corroborate these findings. Psychological constructs influencing verbal fluency were examined in one study which compared young and older adult healthy controls with people with Alzheimer’s or Parkinson’s Disease. Amongst the researcher’s results they found that processing speed was the strongest correlate of verbal fluency performance and they conclude that
‘the primary role of processing speed in performance suggests that the use of fluency tasks as measures of EF or verbal ability warrants reexamination‘
A small study showed a significant inverse correlation between hippocampal volume and CSF p-tau levels in people with Alzheimer’s Disease. There is a write-up at the Alzheimer’s Forum of an interesting study by Schmidt and colleagues in the Archives of Neurology in which the researchers found evidence for a rapidly progressive form of Alzheimer’s Disease both from their own clinical study and also from a review of the literature. However the authors emphasise the need for further work to confirm these results. MRI data from two studies (n=1349) was used to examine the relationship between cortical atrophy and white matter hyperintensities and infarcts in people with Alzheimer’s Disease and Vascular Dementia in this study. The researchers found that cerebral atrophy was correlated with the number of infarcts in people with Vascular Dementia but not Alzheimer’s Disease. An American Committee have revised the criteria for post-mortem diagnosis of Alzheimer’s Disease. The three criterion used are the Braak staging for Neurofibrillary Tangles, Amyloid Beta measures (based on the work of Thal and colleagues) and a CERAD score for neuritic plaques. There is further discussion at the Alzheimer’s Research Forum on these changes. A moderately sized study (n=224) provided no evidence of an effect of cholinergic burden on cognition in people with Alzheimer’s Disease. The researchers compared people with low and high cholinergic burdens and found no significant difference between the two groups. The Alzheimer’s Research Forum reported on the recent Clinical Trials in Alzheimer’s Disease Conference in a series of articles (see here, here, here, here, here, here and here). The coverage includes new developments in Clinical Trials and a closer look at the use of the EEG. In the recent World Alzheimer’s Report 2011 it is estimated that 36 million people around the world with dementia have not yet received a diagnosis.
A role for Early Onset Alzheimer’s Disease related protein Presenilin-1 in a homeostatic scaling a form of synaptic plasticity has been identified in one study. There is a paper (freely available here) on MRI findings in neuroferritinopathy which include Basal Ganglia cysts, cerebellar and cerebral atrophy as well as gliosis. In a recent research study (paper freely available here) the researchers combine resting state and event related fMRI with event related potentials to better characterise the progression from Mild Cognitive Impairment to Alzheimer’s Disease. The researchers in a moderately sized SPECT study investigated aberrant motor behaviour in Alzheimer’s Disease. The researchers draw parallels between aberrant motor behaviour and Obsessive Compulsive Disorder which are supported by the increased uptake of the tracer 99Tc(m) hexamethylpropyleneamine oxime in the OrbitoFrontal Cortex compared to people with Alzheimer’s Disease without aberrant motor behaviour. There is a write-up of the 2011 Alzheimer’s Association International Conference at the Alzheimer’s Forum. Included is some positive news on Bapineuzumab. In a number of trials the use of Bapineuzumab was associated with brain swelling in some of the people taking part. Researchers at the conference presented evidence to suggest that this is associated with treatment efficacy and can be managed without significant complications. However the Phase III trials are ongoing.
At the Alzheimer’s Research Forum there is an interesting write-up of research currently underway in Colombia which involves families with early-onset Alzheimer’s Disease. The write-up emphasises some of the profound ways in which early-onset Alzheimer’s Disease affects families. In one study, the researchers looked at the sensitivity of the ADAS-cog instrument in people with Alzheimer’s Disease. They found that at different stages of the illness, different components of the ADAS cog were effective in detecting treatment effects. A Polish group have reported on differences between people with Alzheimer’s Disease and healthy controls in performance on the pocket smell test providing further evidence of the potential importance of odour discrimination dysfunction as a correlate of pathology. In a small study (n=76), researchers used new research diagnostic criteria to establish diagnosis and then assessed a number of biomarkers. In keeping with biomarker findings in Alzheimer’s Disease, medial temporal lobe grey matter atrophy (using MRI) was characteristic of the prodromal Alzheimer’s Disease group but the researchers did not find any significant differences in regional grey matter volume between the prodromal Alzheimer’s Disease group and participants with Alzheimer’s Disease. In a moderately sized study involving people with Alzheimer’s Disease (n=202) there was found to be an relationship between performance on memory and executive functioning and ratings on IADL – a measure of daily functioning. There were also gender differences with attention predicting bathing and eating ability in women while language skills predicted food preparation in men and driving skills in women. Such associations are useful and can be usefully investigated in larger replication studies.
In one study, researchers looked at the function of a single gene SorCS1 which plays a role in Type 2 Diabetes. They looked at the effect of the gene product on the processing of Amyloid Precursor Protein. Disruptions of the processing of Amyloid Precursor Protein are implicated in the pathology of Alzheimer’s Disease. The researchers found that the the SorCS1 protein influenced where the Amyloid Precursor Protein was moved within the cell. Furthermore this location influenced how the APP was processed thus identifying a link between one risk factor for Diabetes and Alzheimer’s Disease. However both Diabetes and Alzheimer’s Disease are complex illnesses influenced by a number of factors and so further research will be needed to see how these findings fit into the broader picture. The New York Times has an interesting write-up of 3 studies showing the benefits of physical activity and exercise in ameliorating cognitive decline. In two of their studies sedentary behaviour was correlated with more rapid cognitive decline when compared to people who had even light levels of activity. A third study showed the benefits of resistance training in slowing cognitive decline. In another paper from the Alzheimer’s Disease Neuroimaging Initiative the researchers looked at data from 401 people with Alzheimer’s Disease and concluded that CSF ABeta42 levels were elevated in the earlier stages of the illness and that adjusted hippocampal volume and CSF Total Tau levels were altered later in the disease process. The researchers in a small German neuroimaging study (n=31) provided evidence of a relationship between connectivity in frontal-parietal networks and attention (assessed using the Attentional Network Task) in people with early Alzheimer’s Disease. A moderately sized study (n=239) in a sample of people over the age of 85 showed a significant inverse correlation between intracranial volume, which the researchers used as a proxy marker of premorbid brain volume and risk of Dementia and more specifically Alzheimer’s Disease and Vascular Dementia. Interestingly in the group with the largest intracranial volume, dementia risk was not associated with white matter lesions. There is a write-up of the 2010 Leon Thal Symposium which covered amongst other subjects the establishment of a registry as well as approaches to data gathering. An American group have estimated the incidence of dementia and cognitive impairment not-dementia in the USA and over a 6 year period they estimate that there are 1.4 times as many incident cases of cognitive impairment not-dementia as cases of dementia. NICE have just published their revised Technology Appraisal for drugs for Alzheimer’s Disease here.
Over at the Alzheimer Research Forum there is coverage of a small longitudinal study which shows a greater rate of atrophy in Alzheimer’s Disease associated brain regions including the parahippocampal gyrus. However it would be useful to have a larger replication of the data as well as a l0nger follow-up period (this follow-up period in this study is 2 years). Additionally while atrophy in various structures such as the Medial Temporal Lobe are good predictors of conversion to Alzheimer’s Disease atrophy doesn’t necessarily result in disease. Thus Alzheimer’s Disease conversion rates over a longer follow-up period would usefully add to these findings. There is a critical reviewof the use of a combination of Memantine and an ACHEI in the march edition of the neurologist. The researchers identified one relevant study and concluded that there was insufficient data to determine if the statistically significant improvement in outcome measures such as ADL’s was clinically significant. The researchers in a 3-year longitudinal Swedish study of people with Alzheimer’s Disease taking Donepezil (n=435) concluded that the there was an average 1.6 point deterioration in ADAS-cog points every 6 months (although there was no placebo group for comparison). Furthermore the cognitive performance predicted the scores on functioning. Functioning in turn was related to the risk of admission to a residential home. Thus the researchers were able to determine the benefits of medication using a cost-analysis with admission to a care home as one of the outcome measures. There is a write-up of the 2011 International Conference on Alzheimer’s and Parkinson’s Disease in Barcelona at the Alzheimer’s Research Forum. Feedback from the conference includes a more critical discussion of the Amyloid hypothesis as well as a consideration of multimodal therapeutic approaches.
The Lou Ruvo Center has recently opened in Las Vegas. This is a memory clinic with a large investment which impacts on the model of care. The facilities for the memory clinic are contained within a single building and these include a 3 Tesla MRI scanner, facilities for neuropsychology assessment and handheld computers for use in a streamlined process. Interestingly although the patients do not have to enrol in research their data can be compared to the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Also at the Alzheimer’s Research Forum Li and colleagues review the evidence on homocysteine as a risk factor for Alzheimer’s Disease. They conclude that the evidence points to a relationship between homocysteine levels and Alzheimer’s Disease but studies investigating a role for Vitamin B have produced mixed results. In this 11 C PiB study there was found to be no association between Beta-Amyloid load and rate of cortical atrophy over time. Pittsburgh B is a compound which is used to identify Beta-Amyloid Plaque which is central to the Alzheimer’s Disease process according to the Amyloid Cascade Hypothesis. Nevertheless the findings in this study may point to independent roles for Amyloid Beta load and cortical atrophy in the development of Alzheimer’s Disease. The authors of a meta-analysis with a large sample size (n=6122) concluded that whilst there is an association between Homocysteine levels and Alzheimer’s Disease causality has not yet been established and further studies are needed.
Gantenerumab, a monoclonal antibody has joined a number of compounds which have been found to clear Amyloid Plaques in the brain. The Amyloid Cascade Hypothesis states that Amyloid plaques found in the brains of people with Alzheimer’s Disease are central to the disease process and so compounds like Gantenrumab by reducing these plaques are thought to be of great potential in Alzheimer’s Disease. However research into the cognitive effects of the plaque removal for Gantenerumab are still ongoing. The clearance of Amyloid Plaques is also associated with Amyloid Related Imaging Abormalities (ARIAS) the significance of which is still being investigated. The Picalm gene product which has been linked to Alzheimer’s Disease has been investigated in one study where the researchers found evidence that it disrupted the ability of Amyloid to interfere with endocytosis which could inform further research in this area. The researchers in this Korean study provided further evidence of differences in the rate of cognitive decline in three forms of dementia – Parkinson’s Disease with dementia, Vascular Dementia and Alzheimer’s Disease. The authors of a meta-analysis of Diffuse Tensor Imaging studies concluded that Mild Cognitive Impairment differed from Alzheimer’s Disease in that in the former there appeared to be sparing of changes in the frontal and occipital lobes whereas in the latter changes were evident in all regions of the brain. There is a review of a neuroimaging supplement in the Journal of Alzheimer’s Disease which looks at developments in this area. In the USA, the Advisory Council on Alzheimer’s Research, Care and Service is convening quarterly meetings to examine issues such as the infrastructure for research into Alzheimer’s Disease. If this model is successful it will be interesting to see if it can be applied elsewhere. The Department of Health have published their action plan for implementing the National Dementia Strategy which is available here and also published their Dementia Commissioning pack which is available here.
There was no correlation between baseline cortisol levels and subsequent Alzheimer’s Disease in the large prospective Rotterdam study. Poor self-perception of health was one of the factors that was significantly associated with fear of developing Alzheimer’s Disease in a telephone survey of 2013 adults. In one MRI study, researchers compared sequential MRI data on people with Normal Pressure Hydrocephalus (NPH), Parkinson’s Disease (PD), Alzheimer’s Disease (AD. This data was acquired from the Alzheimer’s Disease Neuroimaging Initiative) with healthy controls. The researchers were interested in factors that helped to discriminate NPH from AD and PD and the results suggested that ventricular volume and cortical thickness combined were better than ventricular volumes alone (as the latter values overlapped with the AD group). There is a very good article in the Independent on modifying lifestyle to reduce the risk of developing Alzheimer’s Disease based on a recent study examined this contribution in more detail. The long-term consequences of Traumatic Brain Injury was discussed at the Alzheimer’s Association International Conference (AAIC) in the USA and research was presented associating TBI with subsequent dementia although the relationship is complex. At the Alzheimer’s Research Forum there is an interesting write-up of a small research study which combined functional and structural Magnetic Resonance Imaging (MRI) findings. The study provided evidence of increased activity in the hippocampus being correlated with a reduction in cortical volume in a network which has been associated with changes in Alzheimer’s Disease. It will be interesting to see the results of further replication studies.
One of the questions asked in Alzheimer’s Disease research is just how important are the neurofibrillary tangles in the aetiology? This is a useful question to ask because there are a number of people who are found to have significant neurofibrillary tangles in the brain at autopsy but were not diagnosed with dementia during lifetime. The obvious inference would be that tangles do not necessarily result in Alzheimer’s Disease and there must be other factors playing a protective role. Santacruz and colleagues have tried to answer the question by looking at data from two studies – the Nun study and the Adult Changes in Thought study (combined n=821). Using the Braak staging for grading the pathology at autopsy the researchers found that people with severe Braak staging (V-VI) who were not diagnosed with dementia prior to death did have evidence of significant memory impairment. The data was consistent with the Tau hypothesis* which state that the neurofibrillary tangles play a central role in the disease process. In an interesting development, a group at Oxford have used a new scoring system for small vessel disease to show a correlation with cognitive scores. None of the people involved in the study had pathological evidence of Alzheimer’s Disease using Braak staging and the researchers used both a simple measure of cognition (the MMSE) as well as the CAMCOG. Thus the group have shown results which may contribute to a better understanding of the contribution of small vessel disease to cognition with potentially useful clinical applications. In an fMRI study comparing people with Frontotemporal Lobar Degeneration and Alzheimer’s Disease with a healthy control group the researchers found evidence of an association between an increase in activity in the right temporal pole in Primary Progressive Aphasia and aphasia. The researchers suggest that alterations in the connections of the temporal lobe may account for these findings. The researchers in a recent case-control study in Spain (n=690) concluded from their analysis that variations in the Amyloid Precursor Protein gene did not contribute to risk of Late Onset Alzheimer’s Disease (LOAD) in their sample group although effect sizes can be small.
In a small study (n=64) comparing people with Alzheimer’s Disease with controls, researchers investigated the use of EEG in diagnosis. They found that was a small improvement in sensitivity when the EEG left hemisphere alpha/theta index was combined with a number of cognitive parameters compared with cognitive parameters alone. From a theoretical perspective it will be interesting to see other biomarkers correlates of these findings in larger replication studies. The authors of one paper report on two cases of Posterior Cortical Atrophy with different forms of alexia. The researchers found evidence of differential hypoperfusion and it is important these hypotheses will need examination in large replication studies. A small MRI study looked at the diagnosis of Alzheimer’s Disease. The researchers found that more complex models factoring in data on multiple areas in the brain were better correlated with diagnosis than simpler models looking at the Medial Temporal Lobe and it will be interesting to see these results replicated with a larger sample size. There is a paper on Late Onset Alzheimers Disease (LOAD) outlining three new potential pathways in the disease independent of the amyloid pathways and based on Genome Wide Association Studies. There is a write-up of the new American guidelines for genetic counselling at the Alzheimer’s Forum here. The guidelines were issued by the American College of Medical Genetics and the National Society of Genetic Counsellors differentiate between susceptibility genes and genes associated with early-onset Alzheimer’s Disease. Separately an American survey of 276 first degree relatives of people with Alzheimer’s Disease showed that 60% of participants would undergo testing which included APOE4 testing even if it was paid for privately. Also at the Alzheimer’s Forum the team draw attention to a supplement in the journal Nature focusing on Alzheimer’s Disease and freely available here. In a 2-year prospective study including 211 patients with Alzheimer’s Disease the researchers found a number of factors associated with more rapid decline including higher CDR score at baseline and this is a modestly sized study.
A small cross-sectional structural 3T MRI studyshowed a significant volume reduction in the Amygdala in people with Alzheimer’s Disease compared to a control group of healthy older adult participants. A small (n=68) longitudinal study examining vascular risk factors provided evidence of a significant association between the presence of vascular risk factors and the rate of cognitive and functional decline in people with Alzheimer’s Disease and it would be interesting to see a large replication study with detailed psychometry. The researchers also found an association between the vascular risk factors and regional cerebral blood flow which differed between the groups when using SPECT. There is research suggesting that Beta-Amyloid, thought to play an important role in Alzheimer’s Disease can impair the blood-brain barrier. The researchers included a small post-mortem study of 4 people with Alzheimer’s Disease in their study and found evidence of increased revascularisation in the neocortex and hippocampus. This supports the hypothesis that increasing revascularisation would impair the integrity of the Blood Brain Barrier as this process breaks down and reforms the tight junctions between vascular cells that constitute the Blood-Brain Barrier. The researchers have suggested that Beta-Amyloid or another derivative of Amyloid Precursor Protein may be driving the formation of these new blood vessels (angiogenesis). A moderately sized American study (n=139) found evidence that a person’s beliefs about their risk of Alzheimer’s Disease is strongly influenced by the information they receive about that illness and also that in their sample the younger group perceived themselves at more risk of developing Alzheimer’s Disease compared to the older group. However the older group were more likely to report engaging in risk-reducing behaviours. In work investigating the use of Lithium in Alzheimer’s Disease, the researchers report on an analysis of a sample from a larger study in which they didn’t find a difference between the Lithium and Placebo groups in serum Glial Cell Line Derived Neurotrophic Factor after treatment. There are however other positive findings in this area and it will be interesting to see the results of the large multicentred trial when it is completed.
The elasticity of brain tissue was investigated in a group of people with Alzheimer’s Disease and compared with cognitive intact people who were both positive and negative for Pitsburgh B compound (an important marker of Alzheimer’s Disease that can be identified before the disease manifests). The researchers used a technique known as Magnetic Resonance Elastography and found that brain stiffness was increased in the people with Alzheimer’s Disease compared to the cognitively intact control groups. Research has provided evidence that Amyloid Plaques grow in the brain at around 2-3% year. These Plaques are thought to be critical to the development of Alzheimer’s Disease according to the Amyloid Cascade Hypothesis. The original press release from the Society for Nuclear Medicine (SNM) can be found here and in the report based on papers presented at the 2011 SNM meeting the researchers noted that plaques were present in
‘12 percent of those in their 60s, 30 percent of those in their 70s and 55 percent in those over the age of 80‘
The press release also mentions other research which is investigating imaging techniques to visualise the plaques. There is the potential for such investigations to transform clinical practice if the technology becomes widely available and economically viable. In the Amyloid Hypothesis as well as Amyloid Plaques, Tau proteins found within cells are thought to play an important role in the disease process. In a recent study, Professor Feinstein who has been researching Tau proteins for 30 years and his team discovered that when Amyloid was added to neurons it led to the disintegration of the Tau structure inside the neurons instead of the expected Tau Phosphorylation. Furthermore this was associated with the rapid demise of the neurons suggesting to the researchers that the Tau proteins role in forming the cytoskeletal infrastructure of the cell was being compromised. It will be very interesting to see further replication of these results. There is a write-up of preliminary findings with Leviteracetam in people with Alzheimer’s Disease but there will need to be larger replication studies. 117 single nucleotide polymorphisms at or near the locus for the Alzheimer’s Disease associated gene SOR1 was found to be correlated with hippocampal volume in a group of healthy young adults (n=936) and it will be interesting to see further research in this area. There is an interesting study in which the researchers found a quite high prevalence of depression in people with Alzheimer’s Disease or Vascular Dementia (the paper is freely available here). The researchers used the DSM-IV criteria in conjunction with the Geriatric Depression Scale in 98 consecutive patients with a diagnosis of Alzheimer’s Disease or Vascular Dementia and found a prevalence of depression of 87%. The authors emphasised the importance of screening and it will be interesting to see further replication of these findings. There is a Dutch cost-effectiveness study of Memantine in moderate to severe Alzheimer’s Disease which is freely available here.
At the Alzheimer’s Forum there is a detailed discussion of a new meta-analysis on the relationship between hypertension and Alzheimer’s Disease. The study actually shows that hypertension is associated with a slight lowering in blood pressure which is the opposite of what you might expect if hypertension contributed to Alzheimer’s Disease. There are certainly studies which support a relationship between cerebrovascular disease and Alzheimer’s Disease and since hypertension raises the risk of cerebrovascular disease the results of this study do seem a little surprising to me. However the authors of the article note that there is a higher risk of Alzheimer’s Disease in people with hypertension in middle age and there is also the possibility that Alzheimer’s Disease itself may predispose to changes in blood pressure which might confound the results. They conclude that more research is needed in this area and in particular researchers need to focus on tightening up the inclusion criterion for their studies. Over at the Alzheimer’s Research Forum there is a look at new research which may shed light on early-onset Alzheimer’s Disease. Two studies are covered which look at in vitro research in murine fibroblasts comparing wild-type cells with presenilin gene knockout cells. The evidence from these studies suggests that these genes may play an important role in autophagy the process whereby a cell degrades its components. Again at the Alzheimer’s Research Forum there is coverage of an initiative to standardise the collection of metabolic data – the Metabolomics Standards Initiative. Laboratories use mass spectromoter data to describe the metabolic contents of cells but currently laboratories use widely varying methods. A standardisation of methods should facilitate a comprehensive description of metabolites in cells. In turn this information can be used with genomic and other data to better characterise disease process and investigate therepeutics.
A small (n=43) multicomponent cognitive intervention program showed benefit in people with amnestic Mild Cognitive Impairment but not Alzheimer’s Disease in this study. A small study showed preliminary evidence that not recognising difficulties with memory (anosognosia for amnesia) is present not only in people with Alzheimer’s Disease but also in people with amnestic Mild Cognitive Impairment. This was based on an assessment of 25 people with Mild Cognitive Impairment compared with 21 controls. An interesting moderately sized 5-year longitudinal study in China provides evidence that vascular risk factors increase risk of conversion from Mild Cognitive Impairment to Alzheimer’s Disease but also that treatment of these vascular risk factors decreases the risk of conversion. One research group is reporting that the use of a combination of neuropsychological, CSF and structural imaging data on Hippocampal subfields can be used in the assessment of 12-month conversion rates from MCI to Alzheimer’s Disease. There were 120 subjects in the study – using data from the Alzheimer’s Disease Neuroimaging Initiative and it would be beneficial to see these preliminary findings replicated. Were these findings to be replicated further down the line there would need to be a separate piece of work around taking this outside of specialised research centres and into the clinical setting so although interesting the next stage needs to be verification of the findings. In a moderately sized study (n=78) people with Mild Cognitive Impairment (MCI) and a cognitively intact control group were randomised to either a Growth Hormone Releasing Hormone analogue Tesamorelin (subcutaneously) or placebo over a 20-week period. The researchers found that the Tesamorelin group experienced higher subjective cognitive improvement and higher scores on executive and verbal memory tasks than the placebo group. It will be interesting to see the results of further replication studies involving other populations and longer follow-up periods. In a moderately sized cross-sectional study (n=438), the researchers looked at the relation between apathy and executive functioning in people with amnestic Mild Cognitive Impairment and Alzheimer’s Disease. They controlled for a number of variables and concluded that there was a significant correlation between executive functioning and apathy in the aMCI group but it was not possible to see this relationship in the people with Alzheimer’s Disease. The researchers suggests that additional pathology may have obscured the relationship in the latter group and a longitudinal study design would be suitable for testing this hypothesis. There is a PLOS-One paper looking at predictors of conversion from Mild Cognitive Impairment to Alzheimer’s Disease which is freely available here. Using a combination of biomarkers and psychological outcome measures the researchers were able to identify MCI cases which progressed with a sensitivity of 96.43% and a specificity of 48.28%. A Spanish group write about their experience of a 3-year longitudinal study of Mild Cognitive Impairment. Although there is a body of evidence relating amnestic MCI with conversion to Alzheimer’s Disease in their study, the researchers found this was more likely to be associated with multi-domain MCI. An American group have published research in which they identify a syndrome which precedes MCI and which they refer to as Pre-MCI. For those with Pre-MCI 28% converted to MCI or dementia at 3-year follow-up whereas only 5% converted in the Non-Cognitive Impaired group. The researchers identified Pre-MCI as
‘At baseline, Pre-MCI subjects showed impairment on tests of executive function and language, higher apathy scores, and lower left hippocampal volumes (HPCV) in comparison to NCI subjects‘
The researchers in one autopsy study analysed the results of the 1672 brain autopsies in cognitively normal adults. They found that pathology associated with a number of disease processes was present in a modest percentage of cases even though the people had been cognitively normal before death. Cerebral microinfarcts were present in 33% of cases and 6% had Braak stage V or VI for neurofibrillary tangles. Thus the findings suggest that pathology may be present in the aging brain and that this isn’t necessarily associated with cognitive impairment. Nevertheless the pathologies examined here are central to a number of disease processes which affect cognition and it will be interesting to see further research in this area which helps to better characterise the factors which influence whether the pathology does and does not impair cognition.
A small double-blind randomised cross-over study recruiting people with behavioural variant Frontotemporal Dementia (bvFTD) showed a significant improvement in carer rated Neuropsychiatry Inventory (NPI) scores on the day of administration of 24 IU Oxytocin. These early results will need to be replicated with larger numbers of subjects. Hodges and colleagues looked at representation of musical knowledge in a study comparing people with Semantic Dementia and AD with healthy controls (n=47). Using volume based analysis of the structural Magnetic Resonance images they identified decreasing right Anterior Temporal Pole volume as being significantly correlated with impaired performance on knowledge of popular melodies. Although the people with Semantic Dementia performed worse than the AD and control groups on the melody recognition task the relationship with rATP volume also held in this group. Researchers have identified long repeat expansions in the gene C9ORF72 as being linked to both Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. There is a case report on REM sleep behaviour disorder in a person with Frontotemporal Dementia and the authors suggest that this may be a generalisable feature not just of synucleopathies but of degenerative conditions affecting the relevant cortical centres. In an interesting study, researchers used post-mortem and structural MRI data to assess the volume of the hypothalamus in people with Frontotemporal Dementia. They found that the volume of the posterior hypothalamus was significantly reduced in those with behavioural variant Frontotemporal Dementia. In a German study (n-104), the researchers characterised the course of the illness in people with a diagnosis of Frontotemporal Lobar Degeneration. In their study 57% of the people in the study were still living at home and 40% were receiving non-pharmacological treatment. A small 6 week study showed evidence of a significant decrease in Neuropsychiatry Inventory Scores in people with behavioural variant Frontotemporal Dementia compared to a placebo group and it will be interesting to see the results of large replication studies. Diagnostic criteria are central to the diagnostic process in modern psychiatry with multiple established diagnostic systems in place. Revisions of diagnostic criteria should be more helpful in a number of ways including diagnostic accuracy. The criteria for Frontotemporal Dementia (FTD) were recently revised and the researchers in one study wanted to see if this improved the ability to detect cases (sensitivity). In an analysis of 137 brains of people with pathologically established Frontotemporal Dementia the researchers looked at the criteria for behavioural variant FTD and compared these with the previous diagnostic criteria by looking retrospectively through the patient’s casenotes. 86% met ‘possible criteria’ for behavioural variant FTD with the new criteria compared with 53% meeting the previous diagnostic criteria.
A systematic review examining a number of studies (with a total of 768 people with Vascular Dementia and 9857 controls) reinforced the important relationship between hypertension and increased risk of vascular dementia. A short small-sized trial looking at the use of Donepezil in females with Down Syndrome has shown promise in a number of outcomes although it will be interesting to see the results of larger longer-term replication studies. A small Magnetic Resonance Spectroscopy study (n=48) showed that brain metabolite Myo-inositol is increased in a sample of people with Down Syndrome compared to age-matched controls. There was a post-mortem study comparing brains of 4 people with Down Syndrome (average age 66) with 6 controls (average age 70). As Down Syndrome is associated with age related degenerative changes, this study was able to provide useful information in describing age related changes more accurately. The researchers were interested in the number of glial and neuronal cells in the neocortex in both groups using stereological analysis which means estimating 3-dimensional information about the brain from 2-dimensional microscopic slices. Based on their analysis the researchers estimated that in the brains of the sample group with Down Syndrome there were 30% less glial cells and 40% less neuronal cells than in the control group. Interestingly there were similar numbers of cells in the Basal Ganglia in both groups. This may represent a combination of neurodevelopmental and neurodegenerative processes and it will be interesting to how these results might be influenced by therapeutic interventions in future studies.
A post-mortem study (n=761) examined comorbid pathology in Normal Pressure Hydrocephalus (NPH). Since cognitive impairment in people with Normal Pressure Hydrocephalus is not always reversed with shunting the researchers wanted to know whether this might be due to comorbidity. Although there was a large sample set, only 9 patients had NPH and of these 5 had comorbid Alzheimer’s Disease at autopsy. The researchers conclude that irreversibility of cognitive impairment with shunting for NPH in some cases may be due to comorbidity. In a small study (n=20), cerebral acetylcholinesterase (AChE) levels were assessed using the tracer (11)C-MP4A (using PET imaging) in people with Multiple Sclerosis (MS) with secondary progressive cognitive impairment and also in healthy controls. The researchers found that there was no difference in AChE levels between the two groups but within the MS group there was an inverse correlation between AChE levels and cognitive performance including MMSE scores and it will be interesting to see the results of larger replication studies. A large study (n=13000) confirmed that anticholinergic drugs are associated with cognitive impairment. This relationship was already well established but this was a large longitudinal study (n=13003). The researchers used the Anticholinergic Cognitive Burden Scale (ACBS) to investigate the relationship. For medications with a definite anticholinergic relationship there was a small deterioration in the MMSE over the 2 year follow up (by slightly less than a point) compared to the control group. The study is well covered in an article at NHS Choices.
There’s been some interesting work from two personal genomics companies. Using a large sample size, the researchers at these companies have identified new gene associations with Parkinson’s Disease and estimate that up to 25% of the risk associated with Parkinson’s Disease is genetic. The study was published at PLOS Genetics One and the study is covered in detail at the Alzheimer’s Forum here. There is the first in a three part series on Braak’s hypothesis about Lewy Body Dementia. Braak suggests that based on the localisation of Lewy Bodies in the body in a number of studies that Lewy Body Dementia begins in the enteric nervous system before progressing to the peripheral and central nervous system. There are however critics of this hypothesis and the article presents a balanced discussion of Braak’s hypothesis. A group of Neurologists have published a study in the New England Journal of Medicine in which they examined videos of people who reported that they had Parkinson’s Disease. Based on the Neurologists’ observations of video segments and not on physical examination, the researchers concluded that many of the videos did not show Parkinson’s Disease. The study raises a number of questions.There has been a new characterisation of the 3-dimensional structure of the alpha-synuclein protein associated with Lewy Body Dementia which should contribute towards molecular research in this area (also covered here). One post-mortem study (n=23) found an inverse correlation between number of Lewy bodies in the Amygdala and Amydala volume using prior MRI but no other correlations between MRI and neuropathological findings.
In 2011 there was a Dementia Awareness Week and the Alzheimer’s Society had a report here. Dementia Awareness Week has been well promoted in the media. Carer Tommy Whitelaw toured several cities talking to carers of people with dementia and there is a video interview with him in this article. In Trafford the Alzheimer’s Society staffed an information stand in the local shopping centre and also held a concert at the local Arts Centre. In Dorchester the start of a 3-year roadshow which is a collaboration between the Alzheimer’s Society and Tesco (as the Alzheimer’s Society is Tesco’s Charity of the year) took place. They are hoping to reach 100,000 people over the 3 years. In Maltby, Lost Chord together with the Alzheimer’s Society held a ‘tea dance‘. In Twerton, there was a sponsored open day at a day centre with the aim of raising awareness and raising funds for the local Alzheimer’s Society. The Alzheimer’s Society in conjunction with Tesco held a ‘Remember the Person Photo competition‘ to raise awareness. In Harlow, there were a number of activities including a collection at a Garden Centre, a reminiscence day, an information stand, singing session and tea dance. There is coverage of the work of HOPE – a group of people living with dementia who are raising awareness in West Sussex here. In Sheffield there were a number of activities including an event featuring a children’s TV presenter, a memory tree, balloon launch and singing. In Warrington the Warrington Arts Council for the Development of Music (WACIDOM) had organised a musical recital and there was also a tea event. In Cornwall there was a tea dance organised by the Alzheimer’s Society and Cornwall Care.
In a 10-year prospective cohort study, 163 people without cognitive impairment were assessed on their dietary habits at baseline and grey matter volume was assessed 10-years later (using MRI) together with neuropsychological assessments. The researchers found evidence of a significant association between consumption of boiled or baked fish and improved working memory as well as preservation of grey matter volume of 10 years later. The researchers were careful to control for a number of well-known confounders. One of the emerging findings in Alzheimer’s Disease research is a protective role for the Mediterranean Diet. There have been various suggestions for this relationship including a reduction in Cerebrovascular Disease. In one study researchers investigated the relationship between mediterranean diet and cerebrovascular events (n=707). Participants were stratified into low, moderate and high adherence to the Mediterranean diet. The most interesting finding was that there was a significant reduction in prevalence of infarcts in the highest adherence group. The odds ratio for this group (compared to the low adherence group) was 0.64, significant at the 5% level and with the 95% confidence interval between 0.42 and 0.97.
In a small study (n=49), researchers looked at high and low fat diets in healthy people and those with Amnestic Mild Cognitive Impairment. The latter is a condition in which the person has subjective and objective memory impairments and in some but not all people can lead on to dementia. The researchers found that in both groups of people, the low diet was associated with a significant improvement in visual delayed recall. In other words switching from one diet to another improved the ability to recall visual information. Curiously the low fat did not seem to benefit some of the other skills. The researchers also found that the high fat diet changed some of the biological markers in the cerebrospinal fluid (the fluid that bathes the brain) making the pattern more like that seen in Alzheimer’s Disease. This is certainly very interesting research but it will need to be replicated in a larger sample and over a longer time period. What is most interesting about this though is the possibility that this type of research could lead to some very specific guidance on dietary changes that can affect cognition (that will complement some of the interesting findings e.g the benefits of the Mediterranean diet) but we will need to wait and see. There is further support for the benefits of omega-3 fatty acids or vitamin supplements (C, D, E and B vitamins) in minimising cerebral atrophy in Alzheimer’s Disease in this moderately sized case-control study of older adults. One of the findings from a number of studies has been that older adults (over the age of 65) have slower response times than young adults on cognitive tasks.
In the Neurocognitive Outcomes of Depression in the Elderly study, researchers have published findings which show a correlation between reduced stressors and subsequent improvement in cognitive scores (n=213). Decreased social interaction was a predictor of cognitive decline and although this could have been due to confounders, the relationship still held after controlling for variables such as depression status. One of the most interesting questions about antidepressants is why they characteristically take many weeks to reach a full beneficial effect. There are a number of studies which suggest that the antidepressants act to increase the number of synapses between neurons in the hippocampus – a region of the brain involved in memory formation. A recent murine study provides evidence that a class of antidepressants – the SSRI’s act in the hippocampus to cause one class of cells known as the granule cells to revert to a more ‘immature’ form which are able to form new synapses more readily. One research group has been investigating response times in cognitive tasks across the lifespan and provide evidence that this slower response time is in part due to an effort to increase accuracy. Further by inhibiting this tendency, older adults are able to better match the response times of younger adults although aging is still associated with a slowing in response times. In a large Danish study (n=37658) researchers looked at the national registry data on patients discharged from psychiatric care with subsequent diagnoses of dementia. They found a significant reduction in incident dementia with the use of older antidepressants and although replicated with Alzheimer’s Disease was not with other forms of dementia. Large studies of this type raise interesting questions for further investigation and these results could inform smaller tailored studies aimed at further investigating these findings.
A moderately sized (n=547) longitudinal study showed evidence of a correlation between depressive symptoms (using the 15-point Geriatric Depression Scale) and Executive Control Function (ECF) as well as psychomotor speed but not memory (using the California Verbal Learning Task). A Cochrane Database Systematic Review on antidepressants for agitation and psychosis in dementia was published in February 2011. The authors concluded that there were few relevant studies although in some (but not all) of those identified the SSRI’s were associated with fewer side-effects when compared to antipsychotics as well as showing similar results on reduction in behavioural scores compared to comparator antipsychotics. However the performance of the antidepressant in comparison with placebo differed according to the behavioural scales used. The authors call for further studies in this area. In one longitudinal study over 6.8 years (n=572) AF was associated with a Hazards Ratio of 1.38 for all cause dementia with a 95% confidence interval of 1.1 to 1.73 and the researchers recommend interventional studies looking at how successful AF treatment might impact on the hazards ratio.
Obsessive-Compulsive Disorder
There is brief coverage here of a study in the American Journal of Psychiatry looking at Obsessive Compulsive Disorder where the researchers link the orbitofrontal cortex with difficulties in controlling goal directed behaviours. In a review of studies looking at Obsessive-Compulsive Disorder and eye movements the researchers found that there was an association with a subtle impairment in smooth pursuit eye movements but this was not correlated with symptom severity.
Health and Social Care Bill
The Health and Social Care Bill underwent a second reading at the House of Lords this week and there is coverage of the events at the BBC website which includes an extract of the discussion (see also here). There are a number of proposed changes to the National Institute for Clinical Excellence proposed in the Health and Social Care Bill which is currently passing through parliament where evidence is being given to the Public Bill Committee. Included in these changes is a broadening of the body’s role to encompass a number of social care policies which has previously come under the jurisdiction of the policy development function of the Social Care Institute for Excellence (SCIE). There has been a response from the Professor Sue Bailey, President of the Royal College of Psychiatrists together with representatives of the other Royal Colleges and other professional bodies to the proposed ‘Health and Social Care Bill’. Readers can see an extract from the letter at the GP online website.
Researchers using a model of hominid migration patterns and climate events have hypothesised that climate change has played a significant role in human evolution. They argue that Homo Erectus manifested a number of behavioural traits that provided flexibility across multiple climates allowing it to persist when other hominids which had adapted to narrow climates became extinct. The possible role of climate change in the rise of humans is covered in this post. In a paper published in the Proceedings of the National Academy of Sciences (freely available here) one group of researchers have used a large dataset to analyse genetic variation in human populations in Africa. Previously it has been thought that global human populations originated in East Africa. The researchers in this study confirmed previous findings about genetic diversity in specific ethnic groups in Africa including the Khomeni bushmen of Southern Africa and concluded that human populations originated in Southern Africa. However there is an interesting commentary from Professor Chris Stringer in this article that places these findings in context. There is a very interesting finding in Science reported on here (see also supplementary material here). The genome from a lock of hair from an Australian Aborigine was analysed and compared with genome data from other ethnic groups. The researchers used a number of gene markers to estimate migration patterns. They concluded that Australian Aborigines are the oldest continuous human population outside of Africa and were the first of a wave of humans leaving Africa to populate the rest of the world. They estimate that this happened approximately 62-75,000 years ago. This was followed some 25,000 years later by a second wave of migration that populated Europe and Asia. However the evidence suggests that all groups hybridised with a Neanderthal population in the Middle East before the migration.
An interesting development is the recent publication suggesting that children were taught how to produce the cave paintings found in caves throughout Europe. These paintings are relevant to discussions about the development of symbolic thought in human evolution. Much can be inferred about the neolithic or paleolithic mind from cave art and in this regards there have been interesting findings with the Britain’s oldest example of Cave Art (circa 14,000 years ago) as well as recent findings in Germany. A look at the role of older adults in the Bronze age is covered here. The researchers looked at a 600 year period in Austria approximately 4000 years before present. They found that older adults were more likely to be buried with copper axes than younger males and as this was believed to be associated with higher social status it suggests that older adults held important positions within the community. The common understanding of the origins of language have been challenged by a recent paper. Chomsky suggested that humans have an inbuilt brain mechanism for generating the grammar of a language. A new study involved running simulations on language generation using likely geographical locations for the origins of language as well as data on commonly used terms and phonemes. The simulations suggested that language is likely to have originated in central Africa and that grammatical rules are likely to have arisen through cultural rather than innate biological mechanisms and it will be interesting to follow the subsequent debate. There is a write-up here. There is a replication study on Twitter looking at Dunbar’s number. Professor Robin Dunbar has hypothesised that 150 is the number of social contacts that people are able to meaningfully maintain. The researchers analysed the twitter conversations of 1.7 million people and concluded that the number of stable relationships was between 150 and 200. While there are many reasons for using Twitter which mean that there will be significant variation from these numbers in individual cases the key finding here suggests that people use Twitter socially in a similar way to other forms of social interaction. There is a brief report on a recent paper on the evolution of emotional expressions which take into account anthropological findings of expression across cultures. There is evidence that languages are transmitted through males.
In a paper in the American Journal of Human Genetics, Stoneking and colleagues have looked at the genomes of people from 33 populations in Asia for similarities to the genome of Denisovans. Denisovans are an extinct hominid with one specimen being identified in Siberia dating back to over 30,000 years ago. The researchers found evidence of Denisovan DNA in people living in countries including Australia and Indonesia. They have suggested that the Denisovans were likely to have inhabited a vast range from Siberia to Australia thought to be possible only for modern humans. However other researchers have suggested that hybridisation may have occured in Central Asia with the migration of subsequent generations. The Denisovan specimen was found with a necklace and is more closely related to Neanderthal (although distinct) than humans although such generalisations should be viewed with caution without a sufficient sample size. There is evidence that Neanderthals ate shellfish some 150,000 years ago in the Iberian Peninsula. The earliest evidence in humans dates back to 164,000 years ago in South Africa. The significance of these findings is that consumption of shellfish was thought to differentiate humans from other ancient hominids and to have contributed to population expansion. John Hawks has been involved in genetic analysis of the Denisovan hominin which appears to have diverged from human lineage 400,000 years ago and from the Neanderthal lineage 330,000 years ago. The significance of this is that there is evidence that humans have interbred with both Neanderthals and Denisovans on the basis of recent genetic analyses in humans. However a new specimen suggests that Neanderthals and Denisovans may also have interbred producing a complex genetic history. There is also evidence that Neanderthals were building structures using mammoth bones some 44,000 years ago.
There is also an interesting open-access paper on Neanderthals and fire use in the Proceedings of the National Academy of Sciences here. The researchers looked at a number of sites used by archaic hominids in Europe and found no evidence of fire use by predecessors to the Neanderthals (e.g Homo Heidelbergensis) but repeated fire use by Neanderthals across sites. Although there is evidence of fire use by Homo Erectus at Koobi Fora (estimated at 1.4 million years before present) the evidence here suggests that Neanderthals were consistently using fire and this raises questions about how this consistency was achieved. For instance this may have been achieved through language. A current controversy in the literature centres around whether hominid brain size increased as a result of cooking or preceded this and so this has other implications. Indeed there is coverage of a paper published in PNAS about the origins of cooking. Cooking allowed for selective changes in the jaw and size of teeth in primates. By looking at fossil specimens and using the features of the jaw and teeth as proxy markers of cooking activity, the researchers hypothesise that cooking began approximately 1.9 million years ago. Other research suggests that cooking may have influenced the increase in brain volume that occurred in primate evolution. Contextualising these findings it’s also interesting to ask if early humans (Homo Sapiens) in Europe learnt their fire making skills from Neanderthals in order to survive in this Ice Age environment.
The findings last year of interbreeding between Neanderthals and humans were widely discussed. In another finding skulls recovered from the Iwo Eleru cave in Nigeria have been dated to 13,000 years ago and have features suggesting a hybridisation between humans and an ancient hominid species the latest specimens of which date to 140,000 years ago in Tanzania. Thus the story of human evolution becomes increasingly complicated. In terms of human evolution a very important part of understanding relates to the behaviour of archaic hominid ancestors. In a recent study, one group has dated a Homo Erectus stone tool factor to between 600,000 and 620,000 years ago. They found a large number of stone tools there which is suggests amongst other possibilities a complex social organisation. In another long term study, one group has identified several Neanderthal sites at high altitude (they were previously thought to be found only in low altitude habitats) in the Greek Mountains. What is particularly interesting about these findings is that these sites were revisited over long periods of time possibly up to thousands of years. There is preliminary evidence of hominids in Central Asia using stone throwing to hunt prey 1.9 million years ago. A new analysis of the Laetoli footprints suggest that human ancestors started walking upright some 3.7 million years ago.
Right-handedness is likely to be at least 400,000 years old. An analysis of fossil teeth from 400,000 year old hominid specimens in Spain suggests that they were most likely predominantly right-handed. The pattern of wear on the teeth indicated the most likely direction in which the tooth moved against the food and in turn the hand that was likely used for feeding. These hominids are thought to represent Homo Heidelbergensis. Recent evidence suggests that they are the common ancestor of modern humans and Neanderthals. The researchers also looked at European Neanderthal specimens and found similar evidence for right-handedness. While the researchers focused on the evidence for handedness, the significance of this is two-fold. Firstly there is an argument that asymmetry within the brain is necessary for language. The second is that Schizophrenia may arise as a result of inteference with the development patterns of asymmetry in the brain which is a theory developed by Professor Tim Crow (see review here). These findings could provide the first evidence that another species Homo Heidelbergensis had developed language as well as the possibility that some members may have been affected by Schizophrenia (assuming aberrant neurodevelopmental processes) in Europe as far back as 400,000 years ago. The authors of an Austrian study looking at human skulls concluded that the anatomy of the skull is highly integrated and that changes in one part have significant effects on the structure of other parts of the skull which has implications for considering how adaptations to the environment may have unexpected effects.
Domestication of animals has played an important part in recent human history and possibly in human evolution. The earliest evidence for domestication in dogs has been found in Siberia and dates back to 33000 years before present. Researchers have found a skull which has features of both domesticated dogs and wolves suggesting it is an ‘incipient dog’ i.e a dog in the earliest stages of domestication. However they also conclude that there are no living relatives and so this was ultimately an unsuccesful episode of domestication. What is also interesting is that based on other findings the domestication of dogs took place in many different regions possibly independently. Archaeologists in China may have discovered the first imperial palace which was built at a time of great significance in Chinese history. Meanwhile in Turkey in the eight millenium BC, archaeologists have discovered that bracelets constructed from Obsidian during this period were polished using remarkably accurate methods comparable to those used today according to the researchers and shedding light on an important phase in the history of development of modern civilisation. On Mount Aratat, archaeologists are investigating structures built during an important transition from the Pleistocene to the Holocene epochs during the Younger Dryas. Nearby archaeologists are working at the site of Gobekli Tepe to uncover the origins of agriculture which was to have a profound effect on the course of human history (see here, here, here, here, here, here, here, here and here).
Evidence that Chimpanzees have empathy is provided in this study in which their vocalisations were dependent on the audience of other Chimpanzees. There is evidence that baboones reason using analogy. In one study, the researchers presented Baboons with pairs of shapes and to complete the task the Baboons had to draw inferences about the relations between those relationships. The Baboons were able to complete the task after a learning period and were able to relearn the task much more quickly when it was presented again one year later. Researchers have used obtained evidence that Marmosets can intentionally meditate in order to receive a reward (see write-up here which also features footage). The researchers used an EEG to record brain activity. The Marmoset would appear to focus at a distance and this would correspond to a 12-16 Hz frequency of cortical activity. Once the reward was received there would be a return to waking brain activity. This raises important questions about intelligence, cognitive abilities and consciousness in New World Monkeys whose ancestors diverged from ours some 40 million years ago. There is an open-access article on primate evolution at PLOS Genetics. An international group of researchers have looked at variation in 54 genes in primates in order to produce a more accurate phylogenetic tree.
Phylogenetic Tree from (Perelman P, Johnson WE, Roos C, Seuánez HN, Horvath JE, et al. (2011) A Molecular Phylogeny of Living Primates. PLoS Genet 7(3): e1001342. doi:10.1371/journal.pgen.1001342)
The diversion of human and Chimpanzee lineages is estimated to be between 6 and 7 million years ago from this analysis. There analysis sheds light on some of the earlier and more controversial diversions particularly regarding the New World Primates. A research group from St Andrews in Scotland observed Chimpanzees in Uganda and concluded that Chimpanzees were using at least 66 gestures to communicate with each other. The use of gestures is thought to be an important step in the development of spoken language. The researchers in one study concluded that Orang-Utans are capable of using pantomiming to communicate with other Orang-Utans or with humans. The researchers watched 7000 hours of footage of Orang-Utans in Borneo filmed over 20 years and identified 18 examples where pantomiming was used including the clip shown below. The use of gesturing has been suggested as an important stage in the evolution of human language (see here).
A young orangutan pantomimes for help with a coconut from Science News on Vimeo.
An Origin for Language?: Some remarkable research hinting at the origins of language has been carried out by a UK group with the Bonobos at Twycross Zoo and has been published in PLOS One (see also a write-up of the study here). At the time of testing the Bonobos form two groups each with their own enclosure. The 2 groups are released from their enclosures separately to forage for food. Kiwi is favoured by the Bonobos but they also receive apples and these fruits were stored at specific locations. Bonobos communicate with a series of calls – barks, yelps, peep-yelps and peeps. The researchers recorded the calls that were made when Kiwis or Apples were found. The researchers then varied the food that was presented as well as the recorded calls that were played prior to the groups being released from the enclosures. They found that calls that were associated with Kiwis were more likely to result in Bonobos searching at the Kiwi sites. However there was a small catch in that the Bonobos were more likely to search at the Kiwi sites even without prompting. However after hearing the apple associated calls the Bonobos were more likely to visit the apple sites and so this provided evidence that the calls were likely to represent foraging signals to other group members. There was also a similar result in terms of the time spent foraging at the respective sites when the kiwi or apple associated calls were played back. The researchers suggested that in Bonobos rather than Chimpanzees the combination of different calls is turned into a sequence which has meaning. This ability to combine calls which then have new meaning expands the possibilities for communication and is a significant finding if confirmed. Our ancestors diverged from the Chimpanzee lineage some 6 to 8 million years ago. Since the Bonobo lineage diverged from the Chimpanzee lineage after this, we are related more closely to Chimpanzees than Bonobos in the evolutionary timeline. However if this ability is not present in Chimpanzees then it suggests that this ability to combine calls in humans and Bonobos would be an example of convergent evolution *(1). There was also another interesting finding. One call sequence associated with the Kiwi fruits seemed to be a very strong signal which was associated with the Bonobos searching the apple site twice as often as usual instead *(2). If the Bonobos are distinguished from Chimpanzees through the use of combination calls then this might explain other differences between Bonobos and Chimpanzees *(3) and would contribute to our understanding of the origins of language *(3)
A Mandrill was observed to create a pedicuring tool in this study adding another example to the extensive evidence base of non-human primates using tools. An interesting argument over copyright has developed in the case of an Indonesia Black-Crested Macaque which took a photographer’s camera and photographed itself. The photographs were used by a magazine without asking for permission from the News Agency that employed the photographer. However since the monkey took the photograph of itself it was argued that the photographs were in the public domain. The argument however isn’t that the Macaque itself is the copyright holder. An MRI study of Chimpanzees in captivity and humans showed that there was no brain atrophy in Chimpanzees in contrast with humans. However in cross-sectional studies, the researchers have to rely on comparisons between individuals rather than tracking the atrophy in individuals as in a longitudinal study. If longitudinal data confirms the hypothesis that cerebral atrophy has evolved in humans then we would know to look for corresponding gene differences between Chimpanzees and humans which account for this. In humans though the additional decades of life-expectancy mean that there are many years of environmental stress that would differentiate humans from Chimpanzees making it difficult to distinguish between the effects of genes and environment. In research published in the Open Access journal ‘Mobile DNA’ , the researchers compared human and Chimpanzee DNA and found that the main differences resulted from the so-called junk DNA. The researchers conclude that this is consistent with the theory that the genetic differences between Chimpanzees and humans are mainly differences of gene regulation rather than gene differences. There is an interesting article (via VaughanBell) in Scientific American on group violence across primates. The researchers cite evidence of a relationship between food availability and violent group behaviour. However there is a limit to how much this hypothetical relationship can be used as an explanation for specific instances of behaviours in humans without being informed by high quality data about those same episodes.
Did monkeys gain big brains by ‘shrinking guts’? is the question asked in one paper. The researchers looked at New World Monkeys and after controlling for a number of factors concluded that there was no evidence of an inverse correlation between brain volume and decreasing volume of gastrointestinal tracts (GIT). They used the digestibility of the diet as a proxy measure of GIT size and energy investment in digestion. Nevertheless as Professor Dunbar points out this does not necessarily generalise to humans where the relationship between diet and brain volume is debated. In one study there was a finding of the earliest appearance of nails in primates in T.Brandfi (55.8 million years ago). It had been previously hypothesised that nails appeared with an increase in body size in primates but this finding contradicted the hypothesis. There are various connections between nails, the central nervous system and behaviour. The connexin26 gene for instance relates sensorineural deafness to nail dystrophy. It has also been suggested that nails were selected in place of claws for foraging food on small branches. The nails can also be used for specialised actions including plucking (Thus it might be expected that the utilisation of nails in extending the movement/behaviour repertoire should be accompanied by changes in the Motor Cortex). A large study looked at 125 baboons in the wild in Kenya. The researchers stratified them into 5 social groupings and analysed for two stress-related hormones testosterone and glucocorticoids. Essentially they found that the alpha males, those with the highest social status, were constantly exhibiting the highest levels of these two hormones. The researchers suggest that these results may be translatable to humans. However the alpha male baboons get into frequent physical altercations with other baboons which may contribute significantly to the stress hormone levels and does not translate easily into human settings.
There has been a further interpretation of the findings of Ardipithecus Sediba with the researchers suggesting that the multiple adaptations make A.Sediba a likely candidate as our ancestor, preceding Home Erectus. However this assumption is controversial and others argue that the findings are important because they show that various permutations of adaptations are viable n the hominid lineages. What is also interesting is that the researchers have made the casts of A.Sediba available for researchers around the world which should facilitate the necessary discussion to fully contextualise the findings. There is another article on Austrolopithecus Sediba here. This is important archaeological work going on in South Africa to uncover some of our earliest ancestors that could be called human (i.e part of the genus homo) circa 2-million years ago. They have identified articulated skeletons, are able to gather data on some of the characteristics of the skin of these hominids and have also identified cerebral asymmetry. Debate continues over the nature of the Homo Floresiensis specimens – are they really another species or a human group with microcephaly? Perhaps the genetic analysis underway will settle the matter. A 20-million year old ape skull has been found in Uganda which usefully contributes to the narrative of primate evolution.
There is a very interesting resource on human origins which includes evolutionary and primatology material. Professor Hawks review an interesting paper in PLOS Biology in which the authors discuss several hypotheses about the evolution of human cognition. There is also an interesting Nature piece on human evolution here. The authors of a letter in Nature present a model of the evolution of ‘overconfidence’ which they suggest from their findings leads to an increase in individual fitness although it is also associated with a number of problematic outcomes. There has been a recent computer simulation of human cooperative behaviour the results of which have been published in PNAS. The researchers conclude based on the simulation of their model that people are inherently altruistic and that this results from adaptations to cooperative behaviour. In other words, even if our distant ancestors had started off cooperating for purely selfish reasons the very act of this cooperation over long periods of time creates an environment where altruism emerges as an adaptive trait. There is coverage here of a recent finding of a 160 million year old placental mammal specimen. Hawks also has coverage of the paper here. There are various implications including the possibility that gene mutation rates in hominoids are much lower as well as the interpretation of lineages of early primates. There is coverage of a PLOS-one paper here (via sandygautam) correlating increasing brain volume with maximal oxygen uptake in different species. Again there are various implications and in this context it is particularly interesting to note that Brain Derived Neutrophic Factor is secreted during exercise.
*(1) There is an exception to this. This would not be the case if the Chimpanzee-human concestor was able to combine calls but the Chimpanzee lost this ability after their divergence from Bonobos
*(2) This seemed to me to raise the possibility of deception. There are cases of New World Monkeys specialising so that one member watches for predators while the others eat food. Sometimes this group member will raise a false alarm. When the others move away from the area, this member will then take the food. In the example above it might be possible that the Bonobo on finding the Kiwi fruit attempts to send the other Bonobos to the Apple site so it can secure more Kiwi fruits. What is even more interesting is the strength of this signal as it suggests that the motivation of the signaller before generating the signal might produce a more significant change in group behaviour (i.e it would not just be a function of the motivation of the responding group). If this were the case there may be an interesting correlation between the motivation of the signallers and the effect of the signal.
*(3)As speculation if the line of reasoning given here holds then the combination calls could be as a result of increases in working memory. However working memory capacities of Chimpanzees and Bonobos should be tested directly.
The Royal College of Psychiatrists has started up a YouTube Channel here. The Royal College of Psychiatrists YouTube Channel features a number of interesting videos on their channel including tributes to psychiatrists Professor Sir David Goldberg, Professor Sir Michael Rutter and Professor Hamid Ghodse. There are aslo a series of videos by a group of trainee psychiatrists which are very interesting. In the UK there has been a shortage of doctors going into psychiatry recently. There has been a lot of discussion about how to solve this recruitment problem. I think these two videos could signal a new and profound development in the relationship between psychiatrists and society. In the first video, a group of trainee psychiatrists tell us why they like what they’re doing. During the course of the video we get to see the ‘human side’ of the trainees.
They are a group of young people who share with us a passion for what they are doing. They are relaxed and friendly in their manner and challenge some of the stereotypes that have been developed over the years. Indeed there are very strong stereotypes that have to be challenged. It’s difficult to know where these stereotypes have come from but certainly in the cinema psychiatrists have a very useful role in plot devices leading to well publicised caricatures. This has been well explored in the literature and the interested reader is directed to several resources (see here, here, here and here). Trainee psychiatrists have been engaging with society in other media (see reviews here and here). However the important development here is for the psychiatrist to be shown not as an agent observing and influencing society from the outside but as part of society. In other words people who just happen to be psychiatrists. In this way people will not need to overcome stereotypic assumptions in the simple act of relating to someone who is a psychiatrist. This in turn might contribute to career choices (although research is needed in ths area). In the second video Dr Kamran Ahmed does a brilliant job of tackling these issues.
Ahmed enlists some talented people to work on the animation and sound producing a trendy video that readily connects with the audience. However the most important part of the video is that Ahmed reveals his own thoughts and feelings about his experiences as a psychiatrist. To do this requires a lot of courage but it is an important part of engaging with society because this is exactly what other people are doing regardless of their profession as part of the conversation that is happening in society. There is one point about the video made by commentators and that is the scene with the psychologist. One of the most important aspects of psychiatry is working within the multidisciplinary team. The work of the nurses, occupational therapists, physiotherapists, psychologists, psychotherapists, pharmacists, social workers, support workers and speech and language therapists is essential in getting people better and each of those roles is critically important in this work. However the video is geared towards challenging some of the assumptions that people, particularly doctors have about psychiatrists and so this video necessarily focuses on the experiences of the psychiatrist. There is a very significant exchange between psychologists and psychiatrists and both fields have become enriched because of this exchange. Again though it is a little difficult to easily discuss the differences between a Clinical Psychology Doctorate and a Medical Doctorate in the context of a short video which is fast-paced and geared towards generating wider debate. I hope that this develops into a wider movement with psychiatrists increasingly using social media to engage with society and joining with members of the other professions to do so. I think these videos are a promising and inspiring start for the profession.
The Centre for Disease Control in the United States has released epidemiological data on mental illness and there is coverage at PsychCentral. There is an interview with the author of a new book ‘The Secret Language Code’ at Scientific American. The author Dr Pennkbaker has been using computerised analysis of text to investigate the content and has produced some interesting findings on the use of pronouns. There is a write-up by Professor Wray Herbert on research on survivors of Hurricane Katrina looking at why some people stayed while others moved out and finding a role for communality. There is a write-up here of a recent study in which the researchers identified a gustatory map in the brain to add to the other sensory maps. There is an article (via sandygautam) challenging the interpretation of recent neuroscience findings. A PLOS-One study suggests that there is room for improvement in release of raw data from research studies and this includes release of data to the Journal that groups submit to. Open data is one of the principles of the Science 2.0 movement. In another study, researchers favoured publishing in Open Access Journals.
There is a piece in the Guardian about prescription of antidepressants. The figures have been compiled using a combination of data from a prescription database as well as census data. The figures show interesting trends across the UK although there are a number of factors which influence antidepressant use and there are various reasons why the actual use may differ. A mixed methods approach would be useful to investigate the trends identified. I received a message on Twitter about a new online magazine by United Academics which is freely available here. The articles are very accessible and in the September issue there is an interesting piece on Biogerontology – the study of the biological processes of aging. The UK government is planning to implement copyright exemptions for data mining and there is further coverage here. The Neuroscience Information Framework 2.0 has a list of over 2200 neuroscience databases here (originally via a MindHacks reference to a Wiki on neuroscience databases). There is an interesting video on the Semantic Web below.
Web 3.0 from Kate Ray on Vimeo.
There’s an interesting open letter regarding the use of blogs in research in which the authors compare the use of blogs with the traditional peer review process (via @EvoMRI). There is a new Wiki site – CognoPedia where you can ‘learn more about the brain, cognition, neuroscience and brain health’. More articles are being contributed to the site. Research into a wave of protests in Spain has focused on Twitter usage and how this related to the subsequent protests. The researchers analysed a very large number of Tweets over the relevant time period and found that the large wave of Tweets resulted from initial tweeting by ‘recruiters’ apparently randomly spread through the network followed by well-connected ‘spreaders’ who were able to connect with a large group of other people. Students in one study preferred in-class teaching to video based presentations giving increased attention in the structured class environment as one of the reasons for this preference (via PsychoBOBlogy ). JSTOR are making archived material before certain dates depending on geographic location freely available. There is a talented psychiatrist Dr Peter Gordon who is producing thought provoking films about psychiatry. The video below is a response to a wake-up call to British Psychiatry by Professor Craddock and colleagues (Video no longer available as of 7. 4.12).
There are also a number of Science 2.0 resources which are relevant to Psychiatry 2.0 including: A Frontiers in Neuroinformatics Article on datamining in the Human Connectome Project, NIH Video and Journal of Visualised Experiments. Video and podcast material on science is indexed at this site. At the time of writing there were 7090 indexed videos, MRI educational resource, MR Connected Automated Pipeline – Linking structural MRI data with diffuse tensor imaging data to build connectomes, O’Reilly Open, Source Developers YouTube Channel, The Open Connectome website.
Diagnostic Systems Including DSM-V/ICD-11
The draft DSM-V criterion for a mixed depressive episode are being expanded to fit more closely with clinician’s experience and there are further details here. The new version of the World Health Organisation Classification of Disease (ICD-11) is displayed in draft version here. This is a work in progress with daily updates and it will allow people to comment from July 2011 onwards. I checked out the Mental and Behavioural Disorders section and there was just a little information there (relating to indexes for mortality) at the moment. The World Psychiatric Association have a very interesting paper on the use of the ICD-10 diagnostic system by psychiatrists. The researchers surveyed 4887 psychiatrists across the world using an internet based survey tool. The use of ICD-10 varied from 0% in Kenya and 1% in the USA to 100% in Kyrgyzstan, FYRO Macedonia and Slovenia. 71% of the psychiatrists surveyed used ICD-10 as their main diagnostic system. DSM-IV was the main diagnostic system for 23% of the psychiatrists surveyed (unweighted). 14.1% (unweighted) of the sample set ‘sometimes’ used a diagnostic system and 1.3% used the older versions of ICD-10 – ICD-9 or ICD-8 for diagnostic purposes. There is also a critical look at DSM-V at ‘Boring Old Man’ which highlights the wider debate in society.
Positive Psychiatry
Have they found a happiness gene? A headline in the media suggests that a happiness gene has been discovered. However I think this is an oversimplification of a complex phenomenon. First of all the researchers have surveyed 2500 adolescents in the USA and assessed their satisfaction with life. They then sampled their serotonin genes (5HTT) and divided these into the long and short forms of the genes. The longer allele of the gene results in more receptors in the neurons and is described as being more ‘efficient’. They found a large increase in satisfaction with life in those with the long form of the gene compared to those with the shortened form. Since serotonin is associated with mood, there is a justification for looking at the relationship between satisfaction and serotonin genes. However there are at least two caveats to these conclusions. The first is that this study has been undertaken in adolescents in the Unite d States and it would be interesting to see if these results vary across age groups. The second point is to look at what role the environment is playing in this. For instance there is a relationship between economic factors and ‘happiness’ in previous studies (although slightly more complex than would be expected) and so it would be interesting to see how economic variations in the environment influence these results as well as other factors which influence the social milieu.
There is coverage of the Second World Congress on Positive Psychology here and here. There is an interesting article on resilience and recent neuropsychiatry findings at Psychology Central. There is coverage of a study showing that laughter was associated with an increase in a measure of blood flow (brachial artery blood flow) compared to when people were watching stress provoking movie clips. There has been a recent consultation on the differences between well-being and happiness which will be useful for the ‘mental health and wellbeing’ movement.
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Appendix
- Paper on oxidative stress in Alzheimer’s Disease – open access http://bit.ly/cLAX7q
- Study investigating Kraeplin dichotomy of schizophrenia and depression (open access) http://bit.ly/djQK8N
- Review of biological insights into antisocial personality (open access) http://bit.ly/ch6rgi
- Paper about conducting research in older adults in nursing homes – open access http://bit.ly/9W02mU
- Study – falls after discharge following inpatient fall – open access http://bit.ly/cBhm9N
- Gait in mild cognitive impairment – open access http://bit.ly/cNG1XG
- Executive function and gait in older women – open access http://bit.ly/chovdl
- Dipstick analysis and detection of UTI’s – open access study http://bit.ly/dnXVSt
- Study – potentially innappropriate prescribing in German older adults – open access http://bit.ly/cCbmPY
- Cognitive health in UK and American older adults – open access http://bit.ly/bruigy
- MELSHA study – examining medication side effects – open access http://bit.ly/ctZd5Y
- Motor skills training and attention in older adults – open access http://bit.ly/9RUbOM
- Effectiveness of counselors actively contacting dementia caregivers – open access http://bit.ly/aIsyO3
- Transfer from secondary to primary care – open access http://bit.ly/bDgqxF
- New approach to examining physical activity in older adults – open access http://bit.ly/coJi2z
- Using self-rated measures to predict mortality – 10 year f/u study – open access http://bit.ly/bFS6h2
- Effects of reminiscence in 10 Danish nursing homes – open access http://bit.ly/dcRtJj
- Cognitive function and mortality in US National Cohort – open access http://bit.ly/9YOXkd
- Prospective study on innappropriate prescribing in older adults – open access http://bit.ly/9C8Qn8
- Lewy Body Pathology without dementia and functioning – open access http://bit.ly/ahcnwb
- Executive functioning and quality of life in older women – open access http://bit.ly/drWN0P
- A national survey of nursing homes – open access http://bit.ly/9O7d8P
- Commentary on innappropriate prescribing in elderly – open access http://bit.ly/bvbzGm
- Risks, ethics and science in China http://bit.ly/cX5OLS
- Decoy pseudogenes http://bit.ly/9JvDwc
- Cog function after antid. tx in late-life depression – subscription article http://bit.ly/bM3tSb
- Positive mental aging – subscription article http://bit.ly/aXUdIX
- Position statement on disaster preparedness in US older adults – subscription article http://bit.ly/bzI6QH
- Resting paralimbic metabolism in older adults with BPD – subscription article http://bit.ly/anajMB
- Medial temporal atrophy and amnestic MCI http://bit.ly/bNe81J
- Older adult antid. & executive function study – subscription article http://bit.ly/aGZSgX
- AD prospective study on incident depression & anxiety in spouses – subscription article http://bit.ly/b4C7dD
- Paper on stigma and Alzheimer’s Disease – subscription article http://bit.ly/dBKPBF
- Pilot study of exergames for older adults with subsyndromal depression – subscription article
- Relationship between pre-and post-cva depression examined – subscription article http://bit.ly/aYtt5z
- Study investigating methylphenidate for apathy in AD – subs article http://bit.ly/dpdVj5
- Systematic review – cognitive interventions in MCI – subscription article http://bit.ly/adcQmbS
- Investigation of memantine and regional cortical metabolism in AD http://bit.ly/cfgN4C
- BNDF variant and hippocampal volume in late-life depression – subscription article http://bit.ly/dtsLhc
- Study investigating SSRI in AD – subscription article http://bit.ly/bLwr9L
- Subcortical white matter lesions and euthymia in older adults – DTI – subscription article http://bit.ly/bdXRlv
- Study on prevalence of MCI according to classification – subscription article http://bit.ly/aI2Rle
- DTI and postoperative delirium http://bit.ly/dAe6gm
- Subscription article – Frontotemporal Lobar Degeneration – benign and malignant forms http://bit.ly/9cenO5
- Subscription article – meta-analysis of ethnic differences in dementia care and research http://bit.ly/czY41k
- Subs article – study on depresive sx and incident dementia in older women http://bit.ly/ccnodp
- Paper on algorithm for discriminating MCI, dementia and normal cognition http://bit.ly/auAyXf
- Paper on weight mood interactions in later life – subscription article http://bit.ly/bAgFAn
- Subs article on late-life depression and TIA’s http://bit.ly/beoqOG
- Study on thyroid disorders in older adults with affective disorders – subscription article http://bit.ly/9DHoQL
- Rotterdam study – retinal vessel calibre and late-life depression – subs article http://bit.ly/acULh0
- Successful aging – qualitative study in older adults http://bit.ly/cIueCe
- Subs article – emotional processing in late-life depression http://bit.ly/a75FSC
- Heart rate variability in depressed elderly – free paper http://bit.ly/cB3zyN
- Study of function, cv med interactions in AD – free article http://bit.ly/9Ni0NB
- Alzheimer’s Disease study investigating psychosocail interventions effects on caregiver depression http://bit.ly/cB5SGd
- Study investigating geriatric depression scale – screening performance http://bit.ly/bxeWs9
- Executive functioning and late-life depression – free article http://bit.ly/d3vWom
- Study investigating symptomatic remission in older adults with schizophrenia – free article http://bit.ly/8ZqL0a
- Anxiety symptoms and sleep quality in older women – free article http://bit.ly/bPKlrq
- Meta-analysis of behavioural approaches to late-life anxiety – free article http://bit.ly/ds5uI2
- Apoe4 and depression interactions in older adults http://bit.ly/cp4xGx
- Melatonin trial for insomnia in people with Alzheimer’s Disease – free article http://bit.ly/aiXwCS
- Meta-analysis of FHx of depression and post-stroke depression – free article http://bit.ly/9GAClZ
- Patterns of MCI after depression tx in older adults http://bit.ly/a4f2nM
- Study on visual hallucinations in dementia – free article http://bit.ly/cZTW4n
- 5 approaches to defining mild cognitive impairment – free article http://bit.ly/aKxYg3
- Symptom profiles in depressed older adults – free article http://bit.ly/9BJKAy
- Modular psychotherapy for older adults with depression – free article http://bit.ly/9YB655
- Insomnia in older adults with generalised anxiety disorder – free article http://bit.ly/cSFpmR
- Baltimore epidemiological catchment area follow-up – service use http://bit.ly/azNnac
- Alzheimer’s Disease study investigates counselling in spouse caregivers http://bit.ly/bY9i30
- Free article – depression and dementia interface http://bit.ly/bCqBD4
- Cognitive profiling in Parkinson’s Disease – Free article http://bit.ly/9xhctz
- Rv of studies on antioxidants and cognitive decline http://bit.ly/a2F4rH
- RCT of tx of behavioural problems in LBD http://bit.ly/8YWG8Y
- Study investigating EMF exposure in Swedish twins and dementia risk http://bit.ly/9SkeAl
- Case study of SSRI, donepezil and hippocampal volume http://bit.ly/cU8okO
- Open access – pathology of medial temporal lobe epilepsy http://bit.ly/aGUtnL
- Subscription review article on MRI in PD http://bit.ly/aa14AS
- Subscription review article on vascular risk factors and dementia http://bit.ly/dkvhxC
- Study investigating characteristics of dementia with and without diabetes http://bit.ly/99iTSF
- “Public Sensationalism and Clinical Trials: How to Address the Challenges of Science?” ( http://bit.ly/dz1ra2 )
- Study investigates LDL range in men in relation to depression and cardiovascular disease http://bit.ly/cHLBqe
- APOE4 and susceptibility to Alzheimer’s Disease in the Indian population (open access) http://bit.ly/b542pj
- Proteome analysis of Wernicke’s area in pple with schizophrenia (open access) http://bit.ly/9pRcsc
- Epidemiology of depression stigma in an Albertan population (open access) http://bit.ly/c1TQNW
- Tool for assessment of medically unexplained symptoms (open access) http://bit.ly/dfJoAQ
- Case report of Brazilian lady with Down syndrome and depression (open access) http://bit.ly/ddb5Su
- The psychotropic effects of jasmine are discussed in this paper http://bit.ly/9EgkBC
- Excellent free resource – Popular Anthropology Magazine http://bit.ly/kU66x
- Delirium and long haul travel – subs article http://bit.ly/cuTSVI
- Prevention of delirium – subs article http://bit.ly/axgZkA
- Meta-analysis – physical health as risk factor for depression in older adults – sub s article http://bit.ly/ciadFW
- Detection of delirium in the acute hospital http://bit.ly/dztLJf
- Cognitive dysfunction and NIDDM in older adults http://bit.ly/bN7vDw
- Teaching undergraduates about ageing – subs article http://bit.ly/ah0ofM
- Gastrostomies in dementia – subs article http://bit.ly/bw6Gpj
- Cognition with intracranial dural arteriovenous fistula – subs article http://bit.ly/azurRH
- C-reactive protein for detecting bacterial infection in older adults – free article http://bit.ly/a0beG3
- Free article on sarcopenia http://bit.ly/9kC3Cy
- Free article – medications and tube-fed patients http://bit.ly/caKnlb
- Free article – supporting people with dementia and sight loss http://bit.ly/aWW04y
- Free article – global mental health assessment tool in older adults http://bit.ly/dldg9S
- Free paper on effects of hearing loss on community support in older adults http://bit.ly/bzy9eI
- Free article on risk gene interactions in schizophrenia http://bit.ly/cHltrp
- Free article on information processing in the nucleus accumbens http://bit.ly/ajQpFI
- Free article on frontal cortex in primates http://bit.ly/9634CG
- Free article on genetic basis of human brain evolution http://bit.ly/aEEgT8
- Free article on white matter in psychiatric illness and learning http://bit.ly/dyqOvK
- Free article on cerebellar nuclei http://bit.ly/b9vZBv
- Free TINS article on genetics of dementia http://bit.ly/cN8fOL
- Subscription article on olivo-cerebellar system and temporal pattern generation http://bit.ly/c28jWL
- Subs article – timing, cerebellum and the granule layer http://bit.ly/aVXAOa
- Subs article on delirium and mortality http://bit.ly/aua4rz
- Subs article on neurobiology of autism http://bit.ly/bBEaTv
- Subs article – abnormal development of the cerebral cortex http://bit.ly/cpQHz9
- Great title – subs article – do all animals sleep? http://bit.ly/9lCATs
- Subs article on DNA recoding and evolution of human cognition http://bit.ly/a49Xdm
- Subs article on barrier mechanisms in the brain http://bit.ly/92YryD
- Subs article on cerebellum and speech production http://bit.ly/b156R0
- Subs article – timing, cerebellum and the granule layer http://bit.ly/aVXAOa
- Subs article – the insula and addiction http://bit.ly/aYnktm
- Subs article immune system and aging of memory http://bit.ly/9djjkh
- Subs article on cell adhesion molecules and autistic spectrum disorders http://bit.ly/b36fBE
- Subs article on animal consciousness http://bit.ly/d5JL46
- Subs article on microsaccades http://bit.ly/9s7pFy
- Subs article on primate visual feedback http://bit.ly/ccWqnr
- Subs article on difference in cingulate cortex between monkeys and humans http://bit.ly/bxok7v
- Subs article on model of prefrontal cortex in social reasoning http://bit.ly/cK8geT
- Subs article on angiotensin and Alzheimer’s Disease http://bit.ly/dl92zY
- Subs article on the prairie vole and social behaviour http://bit.ly/auie0O
- Subs article on age related hippocampal changes http://bit.ly/9mxP7d
- Subs article on cerebellar granule cell migration http://bit.ly/c12Hrs
- Subs article on retrograde axonal transport and neuronal cell death http://bit.ly/b0eP4U
- Subs article on mammalian gustatory system coding http://bit.ly/dxKuEL
- Subs article on the default mode network http://bit.ly/alsAzb
- Subs article on sex differences in memory formation http://bit.ly/akXJy2
- Subs article on murine research and Alzheimer’s Disease prevention http://bit.ly/9OB9Pl
- Subs article on sonic the hedgehog and the thalamus http://bit.ly/aFTlXL
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- R/V article on the evolution of empathy http://bit.ly/9EaGvB.
- Subscription r/v article on grounded cognition http://bit.ly/dc4g6W.
- Subscription r/v article – the science of personnel selection http://bit.ly/a0yi6g.
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- Subscription r/v article on emotional and social aging http://bit.ly/dm2oFD.
- Subscription r/v article on cognitive neural prosthetics http://bit.ly/dujyl7.
- Subscription r/v article – concepts needed for investigating love http://bit.ly/cwxDEL.
- Subscription r/v article on possible role of hippocampus in imagination and prediction! http://bit.ly/ch7ajp.
- R/V article – ‘multidimensional’ odours http://bit.ly/cw3vOj.
- 2007 r/v article of copper and iron disorders of the brain http://bit.ly/bmtdUa.
- R/V article on ventral tegmental area and reward http://bit.ly/956PrK.
- R/V article of orbitofrontal cortex and decision-making.
- Free 2007 article on medial temporal lobe and recognition memory http://bit.ly/biEBzX.
- Free 2007 r/v article on glia in blood-brain barrier function http://bit.ly/btm22G.
- 2008 r/v article on cerebellum function http://bit.ly/bqzJBp.
- 2008 r/v article on place and grid cells http://bit.ly/9smB2A.
- Free r/v article on passive v active immunity tx for neurodegenerative disorders http://bit.ly/9loItY.
- Free r/v – mechanisms of face perception http://bit.ly/af0ipd.
- Free r/v article on primate auditory cortex http://bit.ly/aoK937.
- R/V of numbers in the brain – evidence that numbers represented in animals http://bit.ly/9EKbu9.
- R/V of diffuse tensor imaging and neuroanatomy http://bit.ly/9L8f52.
- R/V of serotonin and affect – asymmetry of reward & punishment http://bit.ly/ddM6sA.
- Free r/v article by Woolf on neuropathic pain http://bit.ly/d295ET.
- Free r/v article – monoamines and prefrontal cortex http://bit.ly/bp6K24.
- R/V cerebellum and non-motor function http://bit.ly/cWzN9s.
- Free article – advances in microscopy for neuroscience http://bit.ly/8X64Jb.
- Apparently subplate neurons may be particularly susceptible to injury in foetal development http://bit.ly/a6NPAN.
- R/V of subplate in neural development http://bit.ly/a6NPAN.
- R/V of emotion in amygdala and pfc http://bit.ly/cUu6LP.
- R/V of prefrontal cortex in moral judgement http://bit.ly/a3baUX.
- R/V of connectn between nervous & vascular systems http://bit.ly/9mQGEj.
- R/V molecular pathways in frontotemporal lobar degeneration http://bit.ly/9Tuh88.
- Article – why do we still have maternally inherited mitochondrial DNA? http://bit.ly/ceAkpG.
- Free article – r/v of chromatin structure and function http://bit.ly/9OEMMU.
- Free article – rv of p kinase degradation by ubiquitination http://bit.ly/ap45yf.
- Free article – super-resolution fluorescence microscopy http://bit.ly/dmR7dk.
- Cholesterol turnover in the brain – free article http://bit.ly/9NA845.
- R/V of zinc fingers and genome manipulation http://bit.ly/a8gLzE.
- Unnatural amino acids http://bit.ly/bi3CIx.
- R/V of Mitochondrial DNA mutation and aging http://bit.ly/94Sutw.
- Review of screening of genomes with RNA interference http://bit.ly/aHJoEo.
- Coverage of studies suggesting extra alpha-synuclein is pathological http://bit.ly/aB7aNW
- Robots used in hospital in Scotland http://bit.ly/aztYwx & appears to be from this company from acronym http://bit.ly/cbtu4n
- Subs article – Korean study on risk neuropsychiatric syndromes in AD http://bit.ly/9flcz9
- Subscription article – preliminary evidence of mitochondrial haplotype assoc with AD http://bit.ly/crf3iY
- Subscription article – MRI surface mapping study suggests right caudate atrophy in AD http://bit.ly/cuiHKA
- Subscription article – small study showing dissociation of cerebral atrophy and regional cerebral perfusion in MCI & AD http://bit.ly/9RzokN
- Subscription article – classification algorithms useful for AD v Controls but not AD v MCI from ADNI http://bit.ly/aVTD7C
- Subscription article – large cohort study confirms CR1, CLU, PICALM association with Alzheimer’s Disease http://bit.ly/ceiYWk
- Free paper on Portuguese cognitive impairment study – rural v urban prevalence http://bit.ly/bPu8o5
- Important free article on NIH consensus on preventing cognitive decline http://bit.ly/c9076g
- Subscription article – Evidence of slowed retinal response association with early AD http://bit.ly/b8Qa7t
- subs article – risk of cerebral microbleeds (mbs) in memory clinic assoc with baseline mbs + APOE epsilon genotype http://bit.ly/cdCIeN
- subs article – small study showing evidence of impaired dual task performance in VaD http://bit.ly/8Yq9Sh
- Subscription article – ability to manage technology impaired in mild cognitive impairment http://bit.ly/dAINgE
- Subscription article – Evidence of faster rate of cog decline in Alzheimer’s Disease when new vascular lesions http://bit.ly/aPSbkX
- Subscription article – prospective 24 week trial on Rivastigmine in Parkinson’s Disease with dementia http://bit.ly/bHwG9z
- Subscription article – pathological evidence of Lewy Body disease without clinical features http://bit.ly/aRjvjZ
- Subscription paper – semantic impairment in mild cognitive impairment http://bit.ly/cqruVO
- Subscription article – vocabulary and lobar atrophy interact to predict learning in MS http://bit.ly/9EMNYa
- Analysis of ADL’s in 6 x Donepezil studies which should be interpreted in terms of the excluded studies http://bit.ly/aKOCGV
- HMG-CoA reductase inhibitor use in early v late old age and AD http://bit.ly/awr3Zh
- Subscription article – preliminary study investigating use of default mode network in assessment of AD http://bit.ly/diC9T
- Subscription article – Review of epidemiology of dementia in Parkinson’s Disease http://bit.ly/b85XD5
- Subscription article – Review of interactions between NIDDM, depression, AD and PD http://bit.ly/bYAKxs
- Subscription article – review discussing lipid metabolism and Alzheimer’s Disease http://bit.ly/aMjnrI
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- Most concussions estimated to deliver 95G’s http://bit.ly/cNVn3v
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- Study suggests differing degrees of disfigurement may be associated with similar levels of distress http://bit.ly/9PcMGJ
- Caring for sick elderly spouse associated with well-being http://bit.ly/c6L7Ux
- Predicting behaviour using fMRI and analysis of group combinations identifies m.pfc cortex activity http://bit.ly/ahO5pe
- Subscription review suggesting that dopamine may be related to apathy in Alzheimer’s Disease http://bit.ly/9BCJJh
- Small 3T MRI study finds disinhibition associated with grey matter reduction in Bilateral Cingulus & R.M.F gyri, delusions with R.Hippocampus in Alzheimer’s Disease http://bit.ly/aFoHya
- 15 object test useful in discriminating MCI and AD and assoc with activity in bilat Posterior Cingulate & Right Temporal pole http://bit.ly/dgSWT6
- Small study (n=42) shows reduced regional cerebral blood flow in right inferior parietal lobe and anosognosia in Alzheimer’s Disease http://bit.ly/992OMj
- Subscription article – review of exercise and MCI and Alzheimer’s Disease http://bit.ly/aRZSEq
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- APOE4 status has higher assoc with memory dysfunction predominant form of Alz D than executive dysfunction type http://bit.ly/apkaU8
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- Neuroinflammation and Parkinson’s Disease http://www.ncbi.nlm.nih.gov/pubmed/20571974?dopt=Abstract
- Resveratrol converts harmful forms of ABeta peptides in vitro http://bit.ly/9Ka9hT
- New radioisotope with longer half-life than PIB for use in Alzheimer’s Disease research http://bit.ly/9AN1pe
- Hyperploid neurons more likely to undergo cell death in Alzheimer’s Disease http://bit.ly/9oS1bU
- Association between Vitamin D status and cognitive function in older adults http://bit.ly/c71X1K
- Small study suggests apathy and depression associated with impaired memory and attention in MS http://bit.ly/bLd9N5
- Meta-analysis shows white matter integrity differences in Mild Cognitive Impairment and Alzheimer’s Disease – sub reqd http://bit.ly/agjMqb
- PREDICT-HD study suggests mild cognitive impairment is a valid part of the prodromal phase in Huntingtons Disease http://bit.ly/9GKAM7
- Rudeness at work and mistakes http://bit.ly/d8Kt7V
- Study suggesting people with dementia over age of 75 at risk of poor dental health http://bit.ly/96pdf8
- Study (n=312) suggests relationship between MRI findings and longitudinal cog function http://bit.ly/agVb2w
- Subscription needed – the LADIS study – white matter changes and CVA assoc with VaD and MTA with AD http://bit.ly/9FwLXt
- Another study suggests head circumference mitigates against cognitive decline even with cerebral atrophy http://bit.ly/b0aqVs
- Alzheimer’s Disease – desktop vs bedside diagnosis in the future? http://bit.ly/b69Q7D
- Small study which needs replication but suggests stroke risk may change for certain periods after alcohol consumption http://bit.ly/audCcC
- Apathy and depression associated with change from MCI to AD and LBD in one study http://bit.ly/9OfuDr
- Virtual universe support structural balance theory on human interactions http://bit.ly/cVaQ0h
- SIRT1 linked to cleavage of amyloid precursor protein http://bit.ly/aE3hvv
- Huntington’s Disease prevalence underestimated – recent study http://bit.ly/cqvZsQ
- Automated analysis of 3 million vocal utterances can help in language development research http://bit.ly/9i1P2g
- Report on study suggesting emotional response can be reduced in AD http://bit.ly/9XeXhV
- Analysing auditory information – possibly brain similarities between humans and chickens http://bit.ly/aoTPvq
- Benefits of understanding evolution
- Oldest human ancestor or not?
- Von Economo cells enable connections with multiple brain regions Small study finds Von Economo neuron density reduced in ACC in early onset schizophrenia compared to controls http://bit.ly/bTyGKu
- service SMS txt messgs improve goals achieved for people with schizophrenia in small trial n=62 http://bit.ly/cWu7zv
- case-control study – schizophrenia associated with thinner entorhinal cortex http://bit.ly/96glq5
- Review of gamma-osciallations, NMDA and schizophrenia http://bit.ly/aRGyrI
- small chinese study shows benefit of virtual reality cognitive training in older adults with schizophrenia http://bit.ly/dB1ZBZ
- 17% of consecutive outpatients in Co Tyrone study prescribed multiple antipsychotics http://bit.ly/9TIPbl
- Diabetes and patterns of antipsychotic prescribing in Japan http://bit.ly/bZYXdH
- Spanish study on prevalence of smoking in Schizophrenia and cardiovascular risk (n=1704)
- Venkatasubramanian study – case control corpus callosum body/genu smaller in schizophrenia http://bit.ly/br7YCt
- rating voices for male dominance http://bit.ly/aNEpiv
- complex results of experience in driving for detecting hazards http://bit.ly/aWFy9X
- software – Powerpoint – has democratised strategy suggests one researcher http://bit.ly/cHg600
- Intriguing! Grey matter volume decreases and increases with weight in this study of Anorexia Nervosa http://bit.ly/aYHJmM
- GGA3 protein prevents build up of Alzheimer D related enzyme BACE http://bit.ly/cRwzJj
- small study with continuous arterial spin labelling shows reduced frontal + parietal flow in pple with schizophrenia http://bit.ly/cO78zf
- murine study suggests that brain capillaries clear debris http://bit.ly/dBOZjd
- Nature study reveals new cell involved in neurodevelopment + possibly big human evolution role http://bit.ly/9Y9fxa
- ‘Neuron’ study suggests that ‘Junk’ EEG data holds big secrets http://bit.ly/cthEET
- German researchers turn astrocytes into neurons http://bit.ly/dakH1z
- Amyloid imaging conference http://bit.ly/aZaKjw
- Memory stored in DNA via methylation – Nat Neurosci http://bit.ly/9uE2K4
- Different causes of psychomotor slowing in Alz D and Lewy Body Dementia http://bit.ly/dgDaoC
- 35-year longitudinal study – Assoc between psychological stress in midlife females and later dementia http://bit.ly/aOL78N
- small (1)H magnetic resonance spectroscopy imaging suggests involvement of hippocampus in panic disorder http://bit.ly/cEpJP1
- Date from 90+ study suggests increasing prevalence of dementia in oldest old http://bit.ly/axowwB
- cortical ACh low in PD, MSA- PD and SNP subcortical ACh lower in MSA-PD and PSP http://bit.ly/auKc2C
- study suggests more autopsy studies needed to assess FDG-PET in antemortem dementia diagnosis http://bit.ly/cwXPbe
- upper + lower extremity performance related to functional performance in Alz D (n=371) http://bit.ly/d2OlcS
- comparison of progression in Lewy Body Dementia and Alzheimer’s Disease http://bit.ly/9df8Z6
- Kaplan-Meier analysis in Dementia using MMSE scores http://bit.ly/bJt5IQ
- Very small study (n=4) shows evidence of benefits of spaced-retrieval on name-face-occupation in ppl with Alz D http://bit.ly/bcxR4S
- Brushing teeth and cardiovascular risk http://bit.ly/djFx0b
- Should health policy focus on exercise rather than obesity BMJ commentary http://bit.ly/c2g4fHUS heart association approves video games http://bit.ly/bUJgdc
- preventing falls in the community BMJ full article http://bit.ly/bCnnJh
- Small study finds reduced grey matter loss over 2 years in ppl with schizophrenia on cognitive enhancers http://bit.ly/92buEe
- War in Balkans associated with mood disorders http://bit.ly/bgRiwn but not substance misuse.
- TMS v Sham. Benefit of TMS in depression (n=199) http://bit.ly/9MRcgT
- Is anhedonia another risk factor for cardiac events? http://bit.ly/asZL5u
- Facebook group aims to collect 100,000 samples from oil spill http://bit.ly/beHaC5
- Evidence for Mild cognitive impairment prodrome in subj mem imp – I suspect there will be many false +ve’s http://bit.ly/99vafk
- IOP study grey matter and vulnerability for psychopathy traits http://bit.ly/dkxkkl
- Greater purpose in life associated with reduced risk of Alz Dis in 7 year f/u study http://bit.ly/9tluWZ
- MRI study shows hippocampus subfield deficits in PTSD http://bit.ly/ddnsOC
- Vascular depression hypothesis supported by study – categorisation by wm hyperintensities and neuropsych http://bit.ly/d7vyTS
- Frontal striatal and visual systems altered activity in fMRI study of body dysmorphic disorder http://bit.ly/cT8b93
- Small placebo-controlled trial – escit assoc with increased cog function post-cva http://bit.ly/b26Byz
- Hippocampal volume increase in ppl with schizophrenai after exercise http://bit.ly/cQQX5C
- Comparing salaries assoc with less contentment http://bit.ly/bWXoL2
- Psychiatrist visit to confused Gorilla in Zoo http://bit.ly/aqTCaU
- Higher prevalence of apathy & depression in Alz D than Mild Cog Imp in this study (n=245) http://bit.ly/avSHzo
- Brazilian community older adult study (n=15491), prev: Dep – 7%, clin sig dep sx 26%, sig assoc both with cv dis http://bit.ly/czOyeX
- Baltimore ECA Long Study – Apathy sig assoc with functional decline at 13-y f/u http://bit.ly/9eookK
- Replication needed but systemic rv suggests persistent delirium assoc with hypoxia, del severity among others http://bit.ly/aEXsiw
- UK study finds increased dental problems associated with mental illness in community-living older adults http://bit.ly/bODtIk
- Kinematic data during clock drawing helpful in classifying disease in older adults http://bit.ly/aNFwkU
- Homocysteine assoc with hippocampal atrophy in older adults with hypertension (n=80) http://bit.ly/cs7BXT
- Call for discussion of ethical implications of using surveillance technologies in res homes for ppl with dementia http://bit.ly/d9cScU
- Age at which hippocampal atrophy accelerates estimated in ppl without dementia (n=544) http://bit.ly/dD2DHq
- Australian pharmacist-led RedUse project shows reduction in benzo and antipsych use in nursing homes http://bit.ly/af9NQw
- ceiling and floor effects of MMSE explored in Mexican study http://bit.ly/b5vzqc
- Systematic review concludes that clock drawing test should not be used as screening tool for mild cog impairment http://bit.ly/beKKVM
- Educational theories and older adult liaison psychiatry training provision http://bit.ly/8YQBPN
- Interruption of doctors impact on tasks detailed http://bit.ly/cINch6
- study looking at supported employment efficacy – free full text http://bit.ly/baO2JC
- study shows benefit of early intervention in panic disorder http://bit.ly/9vdj0K
- study finds significant differences between psychiatric and non-psychiatric drug adverts in two journals http://bit.ly/aaaca2
- Mechanism of presenilin gene action in pre-senile Alzheimer’s Diseaes cracked http://bit.ly/9yVRwb.
- The Coalition against Major Diseases is setting up a database to share research on neurodegenerative diseases.
- Neat article on the genetics of autism http://bit.ly/bZIIFv.
- Study estimates more deaths at weekends in hospitals – suggests reason http://bit.ly/bH34M5.
- Cognitive decline in people with diabetes more rapid than control group in longitudinal study reported here.
- Free paper on insular cortex response to SSRI’s in healthy volunteers http://bit.ly/cb8wqo.
- Meta-analysis of monotherapy in bipolar disorder http://bit.ly/93k1vi.
- Free paper – small study showing association between reduced glutamic acid decarboxylase (GAD) in PFC and MDD http://bit.ly/c9oQii
- Good response to Lithium in Bipolar Disorder is associated with normal BDNF levels http://bit.ly/d6Yb0t
- PET study finds quetiapine binds preferentially at extrastriatal D2/3R’s similar to Clozapine http://bit.ly/aC7nZL
- BDNF Val66Met SNP rs6265 significantly associated with verbal memory in Swiss study n=333 http://bit.ly/aOMS7P
- Evidence suggesting that Ghrelin secreted in brain regulates cholesterol levels http://bit.ly/d0sHJp.
- Personal genomics data mix-up.
- Scientific American article describing evidence supporting the scanning hypothesis of REM sleep.
- A discussion of advances in computational visual neuroscience with a video interview.
- Brief article on integrating genomics into doctors visits.
- The plan to sequence 100,000 genomes.
- At least 2000 missing gene sequences in the reference human genome.
- Jumping genes vary between individuals http://bit.ly/9aAask.
- Cardio Trace Monitors used to assess arterial stiffness – might have widespread applications.
- Meta-analysis of CBT for people with somatic disease shows benefit for depressive symptoms http://bit.ly/d0ofkE
- BDI-II scores in post-MI patients may include small non-depression related somatic component http://bit.ly/aEShCt
- More evidence for APOE4 but not ACE for incident dementia in older adults http://bit.ly/9Zuw1
- In another study the researchers found that rehearsing items to do the following day just before sleep were more likely to carry them out than people that tried them before going to sleep.
- Delirium care – survey of UK junior doctors http://bit.ly/98vtgI
- White matter changes seen in early Alzheimer’s Disease using DTI
- Association of FTD and Schizophrenia in some families but not others in this study http://bit.ly/cql9Js
- Study (n=909) suggests mental health literacy associated with reduced prevalence of depressive symptoms in older adults http://bit.ly/cg8cbu
- ‘Blood rheology is independently related to cognitive decline in older people’ subs article http://bit.ly/b1DTOP
- Hypothesis – intestinal barrier permeability and dementia – needs testing. http://bit.ly/aKziap
- IQCODE and distinguishing FTD and AD http://bit.ly/8Xwvdz
- Handgrip strength associated with cognitive decline in oldest old http://bit.ly/c69YNW
- Gender specific risks should be considered to delay res/nurs home admission in older adults – subs article http://bit.ly/bXzUCr
- Need to improve labelling, leaflets and education for medications in older adult study – subs article http://bit.ly/9ZpO6e
- Free article – depression associated with more cardiovascular events HYVET http://bit.ly/9YLrrn
- Subs article – large study shows interactions occur in older adults & physical comorbidity prescribed antidepressants http://bit.ly/9wg0va
- Chinese study showing prevalence of cigarette smoking in people with schizophrenia lower than in western studies http://bit.ly/cs7Lb8
- Discontinuation and reinitiation rates of ACHEI’s in Australian cohort http://bit.ly/bGg6DX
- Benefits of mental health staff in homeless services for identifying mental illness in homeless http://bit.ly/bwUn89
- Call in Australia for research and development of mental health services for indigenous australians http://bit.ly/cj7Jod
- Not open access but apparently new wiki guide on mental health http://bit.ly/bjUUne
- Memory and executive dysfunction not account for by COMT expression in 22qll.2 deletion syndrome http://bit.ly/aWhnCH
- Profiles of Australian antipsychotic use – increased in older women with dementia http://bit.ly/cluPoP
- Neat – Australian study aligning fMRI data with US Alzheimers Disease Neuorimaging Initiative http://bit.ly/bwDqic
- Freud in Australia – sparring with Jung even before they went their own ways http://bit.ly/aYxGnm
- Short (6-week) small study (n=105) looking at combination antidep for depression from outset http://bit.ly/bHpKvL
- Small 50 week fluox. bipolar II study without evidence of increased switching to hypomania http://bit.ly/cY7ABs
- International consensus on antipsychotic dosing schedule http://bit.ly/9WX5yV
- Functional assessment may be sensitive for mild cog impairment from this study http://bit.ly/bPWxU9
- Lacunes with depression assoc with higher mortality in this study of older adults (n=499) http://bit.ly/cYaWjR
- Reduced mortality benefits of self-rated friendly humour in large, longitudinal study
- Cog performance and self-reported functioning in PD (open access) http://bit.ly/8X7eBE
- Health white paper for the NHS discussed here http://bit.ly/aB3vUs
- Therapist competence benefit in cognitive therapy http://bit.ly/bRJzBg
- Working memory skills important in piano accomplishment http://bit.ly/cc1PNK
- Problem solving ability associated with bullying and being bullied in childhood http://bit.ly/cMIylo
- Report on study showing association between executive function and bilingualism http://bit.ly/9ZkEoM
- Word-association tasks and relationship break-ups! http://bit.ly/dreQuj
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