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 brain from 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.
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Penttilä J, Cachia A, Martinot JL, Ringuenet D, Wessa M, Houenou J, Galinowski A, Bellivier F, Gallarda T, Duchesnay E, Artiges E, Leboyer M, Olié JP, Mangin JF,Paillère-Martinot ML. Bipolar Disord. 2009 Jun;11(4):361-70. Cortical folding difference between patients with early-onset and patients with intermediate-onset bipolar disorder.
Phillips L. Strategies used by psychotic individuals to cope with life stress and symptoms of illness: a systematic review. Anxiety Stress Coping. 2009. 1-40. Epub.
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Popescu B et al. Blood-brain barrier alterations in ageing and dementia. J Neurol Sci. 2009. March. Epub.
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Reitz C et al. Memory performance is related to Amyloid and Tau pathology in the Hippocampus. J Neurol, Neurosurgery and Psychiatry. 2009. (Epub).
Reser J. Alzheimer’s Disease and natural cognitive aging may represent adaptive metabolism reduction programs. Behav Brain Function. 2009. 5(1). 13. (Epub).
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Rothi L J et al. Errorless practice as a possible adjuvant to Donepezil in Alzheimer’s Disease. J Int Neuropsychol Soc. 2009. 15(2). 311-22.
Rudea A and Schmitter-Edgecombe. Time estimation abilities in mild cognitive impairment and Alzheimers Disease. Neuropsychology. 2009. 23(2). 178-188.
Sabeen S, Chou C, Holroyd S.Abnormal thyroid stimulating hormone (TSH) in psychiatric long-term care patients.Arch Gerontol Geriatr. 2009 Jul 16. [Epub ahead of print].
Sacchetti E, Galluzzo A, Valsecchi P, Romeo F, Gorini B, Warrington L; MOZART Study Group.Schizophr Res. 2009 Aug;113(1):112-21.Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: the MOZART study.
Salvatore P, Baldessarini R.J, Tohen M, Khalsa H-M K, Sanchez-Toledo J.P, Zarate C, Vieta E and Maggini C. McLean-Harvard International First-Episode Project: Two-Year stability of DSM-IV diagnoses in 500 First-Episode psychotic disorder patients. J Clin Psychiatry. 2008. Dec 30. e1-e9. pii.
Samaan Z et al. Migraine in recurrent depression: case-control study. The British Journal of Psychiatry. 2009. 194. 350-354.
Sampson EL, Blanchard MR, Jones L, Tookman A, King M. Br J Psychiatry. 2009 Jul;195(1):61-6. Dementia in the acute hospital: prospective cohort study of prevalence and mortality.
Savitz J et al. Neuropsychological status of bipolar I disorder: impact of psychosis. The British Journal of Psychiatry. 2009. 194. 243-251.
Savva G.M et al. Prevalence, correlates and course of behavioural and psychological symptoms of dementia in the population. The British Journal of Psychiatry. 2009. 194. 212-219.
Saxton J et al. Functional and cognitive criteria produce different rates of MCI. J Neurol Neurosurg Psychiatry. 2009. Epub.
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Shega JW, Ellner L, Lau DT, Maxwell TL.Cholinesterase Inhibitor and N-Methyl-D-Aspartic Acid Receptor Antagonist Use in Older Adults with End-Stage Dementia: A Survey of Hospice Medical Directors. J Palliat Med. 2009 Jul 21. [Epub ahead of print]
Shen J, Moller H.J, Wang X, Chung S.A, Shapiro G.K, Li X and Shapiro C. Mirtazapine, a sedating antidepressant and improved driving safety in patients with major depressive disorder: A prospective, randomized trial of 28 patients. J Clin Psychiatry. Jan 13. 2009. e1-e8. pii.
Shi F et al. Hippocampal volume and asymmetry in mild cognitive impairment and Alzheimer’s Disease: Meta-analyses of MRI studies. Hippocampus. 2009.
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Sigstrom R et al. The prevalence of psychotic symptoms and paranoid ideation in non-demented population samples aged 70-82 years. Int J Geriatr Psychiatry. 2009. Epub.
Simon et al. Prevalence and Correlates of adult attention-deficit hyperactivity disorder: meta-analysis. The British Journal of Psychiatry. 2009. 194. 204-211.
Siwek M et al. Zinc supplementation augments efficacy of imipramine in treatment resistant patients: A double blind, placebo-controlled study. J Affect Disord. 2009.
Somers M, Sommer I.E, Boks M.P and Kahn R.S. Hand-preference and population schizotypy: A meta-analysis. Vol 108. Schizophrenia Research. Issues 1-3. March 2009. pp25-32.
Starrenburg F and Bogers J. How can antipsychotics cuase diabetes mellitus? Insights based on receptor-binding profiles, humoral factors and transporter proteins. Eur Psychiatry. 2009. Epub.
Stauffer V et al. Maintenance of response with atypical antipsychotics in the treatment of schizophrenia: A post-hoc analysis of 5 double-blind, randomised, clinical trials. BMC Psychiatry. 2009. 9(1). Epub.
Szegedi A, Jansen W.T, van Willigenburg A P, Van der Meulen E, Stasses H.H and Thase M.E. Early improvement
in the first 2 weeks as a predictor of treatment outcome in patient swith major depressive disorder: A Meta-analysis including 6562 patients. J Clin Psychiatry February 24, 2009: e1-e10; pii.
Takahashi T et al. Insular cortex gray matter changes in individuals at ultra-high risk of developing psychosis. Schizophrenia Research. Epub.
Takahashi T et al. Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch Gen Psychiatry. 2009. 66(4). 366-76.
Takahashi T, Wood S, Soulsby B, McGorry P.D, Tanino R, Suzuki M, Velakoulis D and Pantelis C. Follow-up MRI study of the insular cortex in first-episode psychosis and chronic schizophrenia. Vol 108. Issues 1-3. March 2009. 49-56.
Taragano F et al. Mild behavioral impairment and risk of dementia: A Prospective Cohort Study of 358 Patients. J Clin Psychiatry. 2009.
Taragano F et al. Mild behavioral impairment and risk of dementia: a prospective cohort study of 358 patients. J Clin Psychiatry. 2009. Epub.
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Taylor D.M, Fischetti C, Sparshatt A, Thomas A, Bishara D and Cornelius V. Risperidone Long-Acting Injection: A Prospective 3-Year analysis of its use in clinical practice. J Clin Psychiatry. 2008. Nov 18. pii. Epub ahead of print.
Thorp AA, Sinn N, Buckley JD, Coates AM, Howe PR. Br J Nutr. 2009 Jun 1:1-7. [Epub ahead of print]. Soya isoflavone supplementation enhances spatial working memory in men.
Toal F, Daly EM, Page L, Deeley Q, Hallahan B, Bloemen O, Cutter WJ, Brammer MJ, Curran S, Robertson D, Murphy C, Murphy KC, Murphy DG.Psychol Med. 2009 Nov 6:1-11. [Epub ahead of print]. Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study.
Tractenberg R and Aisen P. Agreement in Cognitive and Clinical Assessments in Alzheimer’s Disease. Dement Geriatr Cogn Disord. 2009. 27(4). 344-352.
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Tsuang D et al. Visual hallucinations in dementia: a prospective community-based study with autopsy. Am J Geriatr Psychiatry. 2009. 17(4). 317-23.
Uher R et al. Differential efficacy of escitalopram and nortriptylline on dimensional measures of depression. The British Journal of Psychiatry. 2009. 194. 252-259.
Van der Vlies A et al. Most rapid cognitive decline in APOE epsilon4 negative Alzheimer’s Disease with early onset. Psychol Med. 2009. 1-5. Epub.
Van’t Veer-Tazelaar M et al. Stepped-care prevention of Anxiety and Depression in Late Life. A Randomized Controlled Trial. Arch Gen Psychiatry. 2009. 66(3). 297-304.
Velakoulis D, Walterfang M, Mocellin R, Pantelis C and McLean C. Frontotemporal dementia presenting as schizophrenia-like psychosis in young people: clinicopathological series and review of cases. British Journal of Psychiatry. 2009. 194. 298-305.
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Wakabayashi T, Craessaerts K, Bammens L, Bentahir M, Borgions F, Herdewijn P,Staes A, Timmerman E, Vandekerckhove J, Rubinstein E, Boucheix C, Gevaert K, De Strooper B.Nat Cell Biol. 2009 Oct 18. [Epub ahead of print]. Analysis of the gamma-secretase interactome and validation of its association with tetraspanin-enriched microdomains.
Wang L et al. Alterations in cortical thickness and white matter integrity in Mild Cognitive Impairment measured by whole-brain cortical thickness mapping and diffusion tensor imaging. AJNR Am J Neuroradiol. 2009.
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Wehr H et al. Paraoxonase activity and dementia. J Neurol Sci. 2009. Epub.
Whitwell J et al. Voxel-based morphometry patterns of atrophy in FTLD with mutations in MAPT or PGRN. Neurology. 2009. 72(9). 813-20.
Wilkinson D, Róman G, Salloway S, Hecker J, Boundy K, Kumar D, Posner H, Schindler R.The long-term efficacy and tolerability of donepezil in patients with vascular dementia. Int J Geriatr Psychiatry. 2009 Jul 21. [Epub ahead of print]
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Williamson JW, Querry R, McColl R, Mathews D.Are decreases in insular regional cerebral blood flow sustained during postexercise hypotension? Med Sci Sports Exerc. 2009 Mar;41(3):574-80.
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The Amazing World of Psychiatry: A Psychiatry Blog 
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Thanks for the comment and good luck with your studies! Happy New Year! Regards Justin
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ScienceDaily (May 21, 2010) Though it has been prescribed for over 50 years to treat bipolar disorder, there are still many questions regarding exactly how lithium works. However, in a study appearing in this month’s Journal of Lipid Research, resea…
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