Monthly Archives: January 2011

News Round-Up 2010

2010 was an exciting year in many ways. A draft version of DSM-V was published - the American diagnostic manual for psychiatric illnesses. There was lots of controversy and further discussion is still underway. There were new findings on an important region of the brain referred to as the default mode network which may be susceptible to the changes found in Alzheimer’s Disease. The involvement of neuroanatomical structures in cognitive impairment was further investigated and initial results suggest the subiculum is particularly relevant in Alzheimer’s Disease in comparison to CA1-3 while the cerebellum also appears to be playing a role in mild cognitive impairment. Gene therapy is being trialled for Alzheimer’s Disease in one study but in the CONNECT study, Dimebon did not meet its early promise. A new classification approach to frontotemporal dementia has been developed while three new variants of primary progressive aphasia have been identified. The benefits of physical activity in people with Alzheimer’s Disease are further identified in another study. In schizophrenia research, a big finding was the chromosome 22 gene association with hippocampus-prefrontal cortex disconnection. Comparisons between Schizophrenia and Alzheimer’s Disease have been made and there are findings that exercise can increase hippocampal volume in people with schizophrenia while there have been initially promising results for the use of acetylcholinesterase inhibitors in schizophrenia also. The use of Tetris to interfere with traumatic memories and prevent the onset of post-traumatic stress disorder was another interesting approach. An interesting evolutionary hypothesis was that cooking influenced the development of the hominid brain because of the impact it makes on energy consumption. For me the most groundbreaking study of the year was Paabo’s study on the Neanderthal genome. Analysing the DNA from 50,000 year old bones is no easy matter but Paabo’s team sequenced most of the genome and found that they contributed to the human gene pool. There is still a lot more work to be done on the genome but no doubt this will lead to further insights into various aspects of our biology in a quite profound manner.

Dementia

The National Institute of Clinical Excellence have reappraised their guidance on the use of drugs for Alzheimer’s Disease (see here) with the result that the consultation document states that the acetylcholinesterase inhibitors that are already in use can be used at an early stage of the disease and the drug Memantine can be used at the more advanced stages of the illness rather than being restricted to the research setting. The Alzheimer’s Society have produced a more detailed explanation on their website here. The final document is scheduled to be published in March 2011. A small study (n=245)  finding clinically and statistically significant increases in both apathy and depression in Alzheimers’ Disease compared to Mild Cognitive Impairment. A small study finding involvement of the anterior corpus callosum in Amnestic Mild Cognitive Impairment extending to the posterior corpus callosum in Alzheimer’s Disease.

The other was a double-blind study published in PLOS-One. The NHS Choices detailed coverage is here. Essentially they took a relatively small group of people with mild cognitive impairment and randomised them to either a combination of high dose Vitamin B12, B6 and folic acid or else placebo. The subjects underwent an MRI scan of the head on entry to the study and two years later. They found that there was a 30% reduction in the rate of cerebral atrophy in the group on the high dose vitamin therapy. There were a few limitations however. Firstly there is the sample size – they have 168 people included in the final analysis. The second point is that the actual shrinkage is quite small – 0.76% versus 1.08% in the placebo group and over a relatively short time period (2 years) it is difficult to determine the significance of this. For instance, one of the most significant predictors of conversion from one form of MCI – amnestic MCI to Alzheimer’s Disease is the volume of the hippocampus rather than the cerebral volume. Another point is that we don’t know which people in the group were converting from MCI to dementia and the study wasn’t designed to detect changes in cognition between the groups. Still the result is interesting and they add some supportive evidence for the effect being mediated by homocysteine levels although as with the above study replication is needed with a slightly different design to address the above issues.

There was a Small study using Diffuse Tensor Imaging to focus on white matter changes. The authors write that

Present findings suggest that most DTI-derived changes in AD and a-MCI are largely secondary to gray matter atrophy

There were some white matter changes noted however. One small study showed evidence of hypoperfusion in the frontal lobes and hyperperfusion in the parietal lobe in Frontotemporal Lobar Degeneration and a reversal of these findings in people with Alzheimer’s Disease. The authors of one paper have produced a mathematic model of Alzheimer’s Disease progression using ADAS-Cog scores as the dependent variable and basing their results on data from the Alzheimer’s Disease Neuroimaging Initiative. In a moderately sized prospective study with an albeit short follow-up period of 1.5 years, people with incident Alzheimer’s Disease who engaged in physical activity experienced significantly lower mortality than those who were inactive even after controlling for confounders. There wasn’t an association with rate of cognitive decline although there is other data which supports such a relationship. Anosognosia for amnesia was found in people with Alzheimer’s Disease but not mild cognitive impairment in this small study.

Two interesting papers have been published by the Proceedings of the National Academy of Sciences (see here and here). Taken together they provide evidence which suggests that a specific region in the brain known as the default mode network is more likely to develop Alzheimer’s Disease associated pathology due to peculiarities in the way energy is produced in this region. There’s been a good write-up at the Alzheimer’s Forum on this (see here). The researchers are telling an interesting story with many twists and turns.

When we need energy to do various activities we use one of two mechanisms to get that energy. Glycolysis is the process by which glucose is broken down to produce energy. This can take place through anaerobic or aerobic means. When we suddenly sprint over a short distance we need to get energy very quickly if there isn’t much oxygen available. The term used for this type of energy release is anaerobic glycolysis. The schematic diagram below illustrates this process in which glucose is broken down through several steps releasing the energy-producing molecule ATP as well as lactic acid which leads to muscle fatigue.

In the second case, when we are jogging over a long distance, there is more time to get oxygen to the muscles and we are able to make use of another process known as aerobic glycolysis.

The process of glycolysis is linked to another important energy producing pathway known as oxidative phosphorylation. In this reaction, electrons are transferred between molecules involved in the pathway and the end result is that a large number of energy producing ATP molecules are created. This pathway is very good at creating energy.

These two processes – glycolysis and oxidative phosphorylation have been well described and are found in introductory texts in biology and physiology. The researchers in these studies were interested in aerobic glycolysis – that is the process by which glucose is broken down to produce energy in the presence of oxygen. The energy produced by oxidative phosphorylation is so great in comparison with that produced by glycolysis alone that it has often been overlooked when looking at energy use by the brain. This is just one of the ways in which the researchers have been quite innovative in these studies.

If we turn to where energy is needed in the body, we find that the brain uses approximately 20% of the body’s energy consumption. Therefore the issue of how the brain uses energy is critically important. Needless to say the methods by which the brain consumes energy are extremely complex and may involve a sophisticated interplay between the brain’s support cells – the glial cells and the neurons. In order to investigate aerobic glycolysis, the researchers used measures of glucose consumption and oxygen consumption in the brain. By calculating the expected oxygen consumption for the given glucose consumption, the researchers were able to estimate the extent of aerobic glycolysis in different parts of the brain. It was here that there is another interesting twist in the story.  The researchers found that a part of the brain known as the default mode network appeared to account for more of this type of activity than other parts of the brain. The default mode network involves several regions of the brain that are active during ‘wakeful rest’. The network is characterised by a synchronous firing activity of these different regions at roughly once every ten seconds. The network is thought to be associated with introspective activities in contrast with the brain’s responses to events in the environment. Below is a diagram illustrating the default mode network at different stages of development.

There is some evidence to suggest that the plaques that build up in Alzheimer’s Disease are more likely to be found in the regions in this network. So next, the researchers turned their attention to a component of the plaques found in Alzheimer’s Disease – ABeta peptide. Using a radiolabelled isotope which shows up this peptide in the brain, the researchers used PET scans to examine both people with Alzheimer’s Disease and people with high levels of ABeta peptide in the brain but who were cognitive normal. They found that in both groups, the ABeta peptide was more likely to be found in the regions in the default mode network. Furthermore it was more likely in those people with Alzheimer’s Disease than in those without.

While it’s tempting to draw some general conclusions about what this might mean in terms of introspection and response to external events, it is far too early to do so. Indeed it is far too early to even draw conclusions about energy metabolism and Alzheimer’s Disease. The total sample size in both studies was 58 people and so really what these studies are doing is telling us about what areas in the brain are likely to be affected in Alzheimer’s Disease, which mechanisms might be making them vulnerable and how all of this might tie in with the way the brain creates and uses energy. However there is a need for further studies to reproduce these results with a larger group of people and also to test these theories in different ways to see if they stand up to close scrutiny. If these theories do stand up to close scrutiny then they will give us exciting new insights into some of the mechanisms producing Alzheimer’s Disease and offer the possibility of novel therapies based on this understanding. So this will certainly be an interesting area to follow.

There is a write-up of a study published in the journal Neuron in which researchers found that the Alzheimer’s Disease associated tau accumulating in the dendrite interfered with synapse relay between neurons even before evidence of degeneration of the neurons. In Alzheimer’s Disease research, the Gamma Secretase inhibitors have been problematic as they inhibit not only the desired enzyme but also the functions of the NOTCH protein which has many important biological functions. At the Alzheimer’s Forum, the authors write about recent research published in Nature in which the researchers developed a compound that inhibits Gamma Secretase effectively but not the NOTCH protein functions and it will be interesting to follow subsequent research in this area.

In America, there is a region known as the ‘stroke belt’. As the name suggests, this is a region with an increased prevalence of strokes relative to other areas. The researchers in one study found evidence that people in this area were consuming higher levels of fried fish than in other areas and suggest that the saturated fats would counteract the anticipated beneficial effects of unsaturated fats found in fish. In a prospective cohort study of 417 people with intracerebral haemmorhage a small subset underwent post-mortem analysis. 23% of people with lobar intracerebral haemmorhage had pre-existing dementia with 5 post-mortem analyses revealing a combination of Alzheimer’s Disease and cerebral amyloid angiopathy. In the deep intracerebral haemmorhage group the 5 sampled subjects had small vessel disease without Alzheimer’s Disease. The Informant Questionnaire on Cognitive Decline in the Elderly was used to assess cognition in this study.

One study looked at post-mortem brains in a sample with Alzheimer’s Disease (AD) or Lewy Body Dementia. The researchers were interested to learn about Lewy Body Dementia in different age groups. The samples were divided into 70-79, 80-89 and 90+. The researchers found that the frequency of LBD was lower in the two older groups but the cognitive impairment was similar for all three groups. The severity of neuropathology and clinical manifestations correlated only in the youngest group although synaptophysin severity correlated with the clinical severity in the oldest group. Researchers have found evidence of a protective allele – TMEM106B allele against the development of frontotemporal dementia in those with progranulin gene mutations (another risk factor for frontotemporal dementia).

 

NHS Choices have reviewed a recent study investigating the use of self-reported cognitive activity in older adults. The study had a longitudinal design and a reasonable sample size (n=1157). The study showed a positive association between cognitive activity and delayed onset of dementia but was also associated with a more rapid rate of cognitive decline after onset of dementia. There were various interpretations of these results but the authors of the review point out that the results may have been influenced by a number of confounding factors and that replication with adjustment for confounders is needed before firmer conclusions can be drawn. An open access  systematic review of non-pharmacological interventions in dementia has been published here – the researchers find a good evidence base to support various interventions but depending on the outcome measures used. There is a write-up of the Experimental drug pc73 and effects on preservation of memory function and it will be interesting to see further research in this area. Findings from a 2-year prospective multicentre study are outlined in this article.

There have been a number of interesting developments in therapeutics. A neurosurgical study is underway which involve gene therapy for Alzheimer’s Disease. A nerve growth factor will be delivered to cells in the Basal Nucleus of Meynert using an adenovirus vector. A drug 7,8-dihydroxyflavone has been identified which acts on the trk receptors just as Brain Derived Nerve Growth factor does and may therefore stimulate neurogenesis and it will be interesting to follow further studies in this area. A molecule Nmnat2 has been identified which is necessary for survival of neurons in vitro. Increasing levels of this molecule was associated with protection of neurons against insult. Lansoprazole, more commonly used in the treatment of gastro-oesophageal reflux and gastric ulcers has found a new use this time for research in Alzheimer’s Disease. Lansoprazole has been found to bind to a pathological form of tau-protein which is found in the plaques associated with Alzheimer’s Disease and it’s use as a radioligand in PET studies is now being investigated.

Over at the Alzheimer’s Forum there is coverage on some recent genetics papers showing the possible involvement of a number of Progranulin mutations in the pathogenesis of Frontotemporal Dementia. There is coverage here also. Scientific American has an article on neurogastroenterology – the study of the enteric nervous system and has some intriguing comments on how a ‘mental illness’ could affect this part of the nervous system which uses serotonin amongst other neurotransmitters. They suggest that there might be insights into irritable bowel syndrome and it will be interesting to see how this develops. The authors of a small study (n=54) found evidence of reduced response inhibition in subjects with Type 2 Diabetes. A recent study that has attracted media interest is a murine study suggesting that looking at nerve cell death in the retina can be used to predict Alzheimer’s Disease. This is covered in more detail at the NHS Choices site where it is noted that human trials are awaited before such conclusions can be drawn. Several studies providing evidence of an association between amyloid protein-induced damage to the microtubule system in human and murine cells and Down’s Syndrome, Alzheimer’s Disease and atherosclerosis. It will be interesting to see further supporting in-vivo studies.

Brain-Derived Neurotrophic Factor has been suggested as a possible therapeutic intervention in dementia. The authors of a new study reported on here found that slow versus rapid application of BDNF to cell cultures had different effects and this is discussed further in the report. Alz Forum report on a study providing further evidence of an association between Brain Derived Neurotropic Factor and hippocampal volume. A  common allele of the FTO obesity gene is associated with reduced brain volume in the health elderly. Donepezil in a 24-week placebo-controlled trial in Vascular Dementia with ADAS-cog primary outcome and differential effects according to hippocampal volume (n=974). There was found to be a negative finding of an association between metabolic syndrome and risk of dementia (n=749). At the Alzforum, this post links to a report on a recent virtual conference on Mild Cognitive Impairment with a focus on biomarkers. There is further fMRI evidence (n=36) to support discrimination between behavioural variant Frontotemporal Dementia and Alzheimer’s Disease using functional networks – the Default Mode Network and Salience Network. An autopsy study n=168) comparing patients with Lewy Body Dementia (LBD), Parkinson’s Disease (PD) and a control group and the researchers found a significant reduction in comorbid

severe cerebrovascular disease or history of stroke

in the LBD group. There was a negative finding for benefit of statins on cognitive function (n=548) in older adults in one study. A new gene association with late-onset Alzheimer’s Disease has been found using a GWAS (genome wide association study). The gene is MTHFD1L and is located on chromosome 6. A small phase II trial (n=24) of intravenous Gamma Globulin has shown evidence of reduced ventricular enlargement and brain atrophy in people with Alzheimer’s Disease compared to the control group. It will be interesting to see the results of the Phase III study when completed. The American Academy of Neurology have updated their guidelines on driving advice for people with dementia. Loss of muscle mass was associated with Alzheimer’s Disease in one study and a suggested explanation was an association with reduced activity. In another study there was found to be a strong association between ABeta oligomers in the CSF and performance on memory tasks in people with Alzheimer’s Disease. A prospective study (n=2148) looked at risk of Alzheimer’s Disease according to dietary patterns and identified one diet associated with a clinically and statistically significant reduced risk. See here for further details. Dimebon has been a candidate treatment for Alzheimer’s Disease after an initially promising trial reported in the Lancet (see here for further details) and is used in Russia as an antihistamine. However the results of two Phase 3 trials have been recently reported. In the CONNECT study – a double-blind, placebo-controlled trial (n=558), Dimebon did not meet statistically significant improvements on the primary or secondary points relative to placebo. There is still another trial in Huntington’s Disease underway and the company have further information on Dimebon here.

Researcher Kausak Si teamed up with Eric Kandel to investigate the role of a protein called CPEB in slugs. The CPEB is located in neuronal synapses. When the researchers targetted antibodies to CPEB they interfered with the ability to form new memories. They found that CPEB was similar to prions found in Yeast and have speculated that self-replication might play a role in memory formation (although they didn’t have evidence from this study for that particular hypothesis). Prions have been identified in a number of pathological conditions including Creutzfeld-Jacob disease. rather than in health. There is a report here on two studies that looked at processing of emotions in Parkinson’s Disease. One was a meta-analysis that showed a reduction in outcomes of emotional processing across a number of tasks while the other looked at the effects of a subthalamic stimulating device on emotional processing. An Italian group provide evidence that Frontotemporal Dementia can be usefully divided into two broad groupings based on performance on neuropsychological tests (Borroni et al, 2010). A small study (n=12) showed preliminary evidence of a benefit for methylphenidate for apathy in Alzheimer’s Disease and it will be interesting to see the results of further research (Padala et al, 2010). In a large open-label trial (n=4460) response of six symptoms to Rivastigmine in people with Alzheimer’s Disease was assessed using the CGI-C – ‘attention, apathy, anxiety, agitation, irritability and sleep disturbance’ (Gauthier et al, 2010). The authors reported a large proportion of subjects improving in these symptom categories (compared to worsening of symptoms) but the randomised control trial would avoid some of the biases noted by the authors.

Over at AlzForum, there is a report on an interesting finding that histone methylation may be associated with learning. There is also an Alzforum report on research suggesting that impaired neurogenesis could lead to an impairment in cognition preceding some of the more well-recognised pathological changes seen in Alzheimer’s Disease. By using a combination of structural imaging and psychometry, the researchers of one study provided support for a dual-process theory of familiarity and recognition (i.e that these are distinct constructs) (Wolk et al, 2010). The researchers compared controls, people with Alzheimer’s Disease and people with amnesic mild cognitive impairment. Regression provided evidence that familiarity was more closely correlated with extra-hippocampal medial temporal lobe structures while recognition was more closely correlated with hippocampal volume. It will be interesting to see further research using different approaches to investigating this relationship. The authors of one study report progress in the use of radiolabelled iodine-123-metaiodobenzylguanidine scintigraphy in Lewy Body dementia (Treglia et al, 2010). There is a commentary on an association between Alzheimer’s Disease and seizures here. Four papers in the Lancet examining the relationship between blood pressure variability and stroke are reported on in this article.

Two recent studies reported on here have provided evidence that variations in the expression of the gene for insulin-degrading enzyme are associated with risk for Alzheimer’s Disease which is thought to be mediated via the degradation of Amyloid Beta plaque. Thus higher levels of IDE were associated with reduced risk. There is a report on a relatively small study (n=35) which investigated the relationship between family history and amyloid plaque accumulation identified using a combination of Pittsburgh B compound and PET scans. Research in fruit flies has shown the efficacy of a compound – affibody – in both degrading and facilitating removal of ABeta aggregates. One research group has identified a novel pathway involving amyloid plaque mediated excitotoxic cell death in a model of Alzheimer’s Disease which may lead to new therapeutic approaches. There is evidence that build up of Amyloid Beta leads to cataracts in people with Down Syndrome as well as being associated with early onset of Alzheimer’s Disease.

The Alzheimer’s forum (AF) has an interesting post on the relationship between metabolic disease and Alzheimer’s Disease (AD). There is a recent meta-analysis looking at the use of augmentation with acetylcholinesterase inhibitors in schizophrenia and schizoaffective disorder involving six open-label and 24 double-blind RCT’s with the authors showing benefits for memory and performance on the Trail Making Test Part A (Ribeiz et al, 2010) . The authors of a systematic review in the Journal of Neurology, Neurosurgery and Psychiatry concluded that MRI determined white matter hyperintensities had heterogenous pathological correlates and that developing quantitative MRI methods could enhance yield of clinical data. The International Working Group for New Research Criteria for the Diagnosis of Alzheimer’s Disease (AD) have published a paper in the Lancet Neurology in which they propose broader  criteria for diagnosis in the research setting. A small study produced no evidence of an association between AD-related olfactory deficits and Amyloid Beta load using PET with Pittsburgh B compound. There is an interesting case study describing cobalamin deficiency associated executive dysfunction improving with replacement therapy. A recent study showed a significant difference in visual impairment between those with and without subsequent dementia (n=625) although it will be interesting to see if there is a causal link or else explanatory confounders.

A group in China investigated the possible role of the cerebellum in mild cognitive impairment. They compared 26 people with amnestic Mild Cognitive Impairment with 18 controls. Both groups underwent resting state fMRI at baseline and follow-up (at least 20 months later). Those with aMCI were significantly more likely to exhibit a higher amplitude of low frequency variation in the posterior cerebellum. The cerebellum has received little attention relative to cortical areas in MCI and it would be interesting to see further work in this area. At the Alzheimer’s Forum, there is a write-up of a study providing evidence that circulating Amyloid-Beta peptide may be deposited in the brain leading to Amyloid deposition which according to the Amyloid hypothesis leads to Alzheimer’s Disease. This contrasts with other models in which the disease is thought to occur when there is a disruption of clearance of the peptide from the brain into the circulation. A comparison (n=13734) of concurrent antipsychotic prescribing with Donepezil or Rivastigmine found a small (1%) but statistically significant difference with a lower prescribing rate in the latter although the interpretation is less than straightforward.  A small study (n=43) provided evidence of hyperacusis (14%) and tinnitus (19%) in Semantic Dementia which the authors interpreted as possibly related to cortical changes identified using structural MRI although there was no control group in the study. A longitudinal Swedish twin study looked at predictors of developing dementia and identified grip strength and ‘higher emotionality on the EAS Temperamental Scale’ as significant predictors. A small Japanese case control study (n=89) showed evidence of a significant association between Thyroid Stimulating Hormone levels and right Cerebral Blood Flow in Alzheimer’s Disease and it will be interesting to see further research in this area. Researchers in a Brazilian study used texture analysis (TA) on MR images to identify differences between people with Alzheimer’s Disease and amnestic Mild Cognitive Impairment in the area of the corpus callosum and thalamus. Level of education was correlated with performance on the Clock Drawing Test in this South Korean study (n=268). A small study compared people with Frontotemporal Dementia, Lewy Body Dementia, Alzheimer’s Disease and controls and found a prevalence of occasional microbleeds in the control group of 60% as well as a signifiantly higher prevalence within the Alzheimer’s Disease group. Arterial hypertension was the most common risk factor in Alzheimer’s Disease and Lewy Body Dementia. There is an interesting paper on the possible non-progressive nature of behavioural variant Frontotemporal Dementia. In an evaluation of 522 patients who underwent subthalamic deep brain stimulation for Parkinson’s Disease the mortality occurred in 0.7% of cases. Adverse hardware events occurred in 7% of cases and the researchers concluded that deep brain stimulation ‘can be considered as a safe procedure’.

At the Alzheimer’s Forum there is a document outlining the work of the Michael J Fox Foundation which has established a multicentre study to investigate the biomarkers that could usefully predict progression of Parkinson’s Disease – The Parkinson’s Progression Markers Initiative. The approach is analogous to that of the Alzheimer’s Disease Neuroimaging Initiative and the researchers are focusing on alpha-synuclein, DJ-1, ABeta peptide, blood urate levels and CSF tau.  There’s an interesting study looking at frontal lobe symptoms in people with (probable) Alzheimer’s Disease (AD), Lewy Body Dementia (LBD) and Frontotemporal Dementia (FTD). The sample size is large (n=559) with the global deterioration scale being used to assess severity and the Middelheim Frontality Score being used to assess frontal lobe function. The researchers found that AD and LBD severity were significantly associated with increasing Middelheim Frontality scores but the same relationship didn’t hold for FTD. However Middelheim Frontality score was significantly higher in the FTD group than for the other two groups regardless of severity. In the research setting this might be useful in further characterising the pathology of AD and LBD as the illnesses progress and it would be interesting to see further work investigating the association with behavioural changes.

There is a recent report from the longitudinal German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe) on anticholinergics in which the researchers cite a hazard ratio for dementia of 2.081. The study recruits people over the age of 75 and there are more details here. It will be interesting to see further work in this area and the implications may be complex and dependent on comorbidity but are also relevant to the Beer’s Criterion. In a murine model of abnormal amyloid deposition, the researchers found that interrupting the pathway between entorhinal cortex and hippocampus was associated with a lower deposition of plaque. There is a write-up at the Alzheimer’s Forum and the inference is that A Beta peptide is transmitted through synapses and in the comments it is noted that a constant supply is required to maintain plaques. There was a recent conference on Frontotemporal Dementia which is reported on at the Alzheimer’s Forum and includes interviews with some of the participants. There’s further research looking at bilingualism and onset of dementia. There is a brief write-up at the Alzheimer’s Forum of a cross-sectional study showing an association between an older age of onset of dementia and bilingualism. Those who were bilingual had symptoms of dementia  5 years later on average than those that were monolingual. However because this was a cross-sectional study it does not establish causality and so there may be other factors which account for this relationship. Additionally it’s not clear if people can learn a second language in mid-life and still gain the benefits as people in this study were bilingual from early adulthood.

A small EEG study comparing subjects with probable Alzheimer’s Disease with controls showed evidence of an increase in left intra-hemispheric and left parieto-temporal central coherence and a decrease in right temporo-parietal-central coherence in people with probable Alzheimer’s Disease compared to the control group. These differences were interpreted as alterations in cortical connectivity resulting from the disease process. A small study compared dental health in people with Alzheimer’s Disease with controls. The researchers found that people with Alzheimer’s Disease were more likely to leave their dentures in at night-time and that 70% of the people with Alzheimer’s Disease had irregular brushing of their teeth and cleaning of their dentures. A small FDG PET study found that people with vascular patients with dementia were more likely to have metabolic disturbances in the frontal lobes and deep nuclei than vascular patients without dementia. The authors of a systematic review on personality changes in Alzheimer’s Disease found decreases in conscientiousness and extraversion amongst other changes. A brief report on progress in therapy for Alzheimer’s Disease has been published at the Journal of Alzheimer’s Research and Therapy. The authors summarise different strategies being pursued currently including those  targetting the Amyloid-Beta peptide.

A longitudinal study (n=3494) examining the relationship between caffeine intake and subsequent dementia found that there was no significant association between caffeine intake and forms of dementia including Vascular and Alzheimer’s Dementia. There was found to be  a significant difference between those in the lowest and highest quartiles of caffeine intake with those in the highest quartile having a lower number of dementia associated brain lesions at post-mortem. In an article freely available here, researchers detail the post-mortem findings on the first person with Alzheimer’s Disease to undergo PET scan imaging with Pittsburgh B compound. The researchers found a strong correlation between the PET findings and the occurrence of plaques but not tangles at post-mortem. Thus this study lends support to the benefits of Pittsburgh B compound in the assessment process although there are limitations on the conclusions that can be drawn. In a study including 214 subjects – young, middle-aged, older adults and people with Alzheimer’s Disease the latter group were differentiated by performance on a visual motion processing task in which randomly moving dots were presented in the visual field. It will be interesting to see the results of further studies in this area.

A recent paper in the Lancet Neurology reviews developments in behavioural variant Frontotemporal Dementia including a new classification scheme which is characterised by the likelihood that the disease is correct. The September issue of the International Journal of Geriatric Psychiatry looks at national dementia strategies in a number of countries. The authors of a systematic review (open access) of studies looking at communication between people with Alzheimer’s Disease and their caregivers concluded that one technique was particularly effective

the use of memory aids combined with specific caregiver training programs

A small Japanese study showed evidence for factors influencing response to Donepezil including age (inverse), duration of executive dysfunction and time to diagnosis. These are interesting findings but again it would be good to see replication studies with large numbers. In terms of molecular pathology, a recent study from Japan shows evidence of a relationship between insulin resistance and amyloid plaque but not neurofibrillary tangle development. There is other research which has produced different results but there is a write-up of the study over at the Alzheimer’s Forum. After undertaking a systematic review, one group have called for the development of a multidomain rating scale for use in Alzheimer’s Disease and to monitor progress – the paper is open access. A small Brazilian study looked at the interaction between vascular and other risk factors and cognitive decline in vascular dementia. The researchers found that after controlling for vascular risk factors education was significantly associated with decline. This reinforces previous research suggesting that increasing years of education are a protective factor for dementia although the literature also shows that the relationship is complicated and that education influences the rate at which decline occurs.

The authors of a review article in the Journal of Neurology, Neurosurgery and Psychiatry recommend an increase in referrals for genetic testing in cases of EOAD (Early Onset Alzheimers Disease) and IPD (Inherited Prion Disease) on the basis of case ascertainment from two UK genetic testing centres. Higher (but not lower) T3 levels were associated with decreased performance on memory and visuospatial tasks in a small case control study involving people with Mild Cognitive Impairment and healthy controls. The results for other hormones were non-significant. Briefly white matter hyperintensities in parietal networks were associated with deterioration in executive performance in MCI, diabetes at baseline was associated with a higher prevalence of AD and VaD in this large prospective study, larger temporal lobe volume was suggested to be a protective factor for Alzheimer’s Disease when there is a large Beta-Amyloid load in this PET study and specific variants of the Alzheimer’s Disease associated genes CLU and PICALM were associated with cognitive performance in the ‘oldest old’ in this study.

This report highlights recent research findings on biomarkers for Alzheimer’s Disease http://bit.ly/a43CnZ. Names influence career choice in children http://bit.ly/avw4sH. Study -prior brain size not atrophy related to cognition in community dwelling older adults – open access http://bit.ly/dfOVJ8. Ginko Biloba in dementia – meta-analysis shows efficacy compared to placebo – open access http://bit.ly/99m3b8. Diffuse Tensor Imaging was useful in discriminating between amnestic Mild Cognitive Impairment (MCI) and non-amnestic MCI in this moderately sized study (n=418). A structural 3T MRI study (n=50) examining age associated changes in the hippocampus identified these changes in the subiculum but found no evidence  in other subfields. CSF levels of Beta-Amyloid were inversely associated with years of education in this study which recruited 70 people with a diagnosis of Alzheimer’s Disease. Links between DISC1 and APP gene products were identified in this study. The write-up is very good and essentially this research suggests a link between genes associated with Schizophrenia and Alzheimer’s Disease respectively. The functional links were identified in a neurodevelopmental model and involve interactions of the gene products during migration of neurons. On the basis of their findings the researchers hypothesise that the Amyloid Precursor Protein (APP) acts as a scaffold that interacts with the DISC-1 protein to facilitate migration. The role of the APP in Alzheimer’s Disease is different and so this study is not suggesting a link between the diseases although it is becoming clear that these two proteins have important biological functions.

A small PET study (n=42) using 18F-FDG to assess brain metabolism compared people with amnestic mild cognitive impairment with or without awareness of amnesia. The researchers concluded that hypometabolism in the inferior parietal lobule, superior temporal gyrus and angular gyrus were associated with loss of awareness (anosognosia) of amnesia although it would be interesting to see replication with a larger sample. A small structural imaging study recruited 11 people with PSEN1 mutation associated early Alzheimer’s Disease and compared with 18 controls. The researchers found that there was an increase in cortical thickness in the parietotemporal area and precuneus together with an increase in the caudate volume 9.9 years before the age at which onset was predicted. There followed a period of atrophy. This is a small sample but the study generates a very clear hypothesis. Free and delayed recall were associated with atrophy in the CA1 subfield of the hippocampus in this cross-sectional structural MRI study in 35 people with Alzheimer’s Disease. A post-mortem study compared a sample with Alzheimer’s Disease (n=10) with a control group (n=10) and the researchers found that when examining the microvasculature there was a significant association between increasing capillary length density (length per unit volume) in the temporal cortex and decreasing cortical diameter in this region. A longitudinal study is needed to investigate this further.

The authors of this paper make a number of suggestions about post-operative cognitive decline including a focus on codifying episodes. A large prospective study (n=3824)  investigated the relationship of untreated and treated hypertension. The relative risk of dementia incidence with untreated hypertension was 1.9 compared to 1.5 in the drug treated group and relative to a control group who did not develop dementia. There’s a write-up of a recent study which showed a strong correlation between biomarkers and scores on a family/carer rated questionnaire (AD8) for function in people with Alzheimer’s Disease. A study appearing in the International Journal of Geriatric Psychiatry looked at prescription of antipsychotics in the last 90 days in people living in the community or in care homes in England and Wales by analysing a primary care database. 3677 patients were identified in the community and 2173 in care homes. Antipsychotic prescription was 0.9% in the community and 20.9% in the care homes in the last 90 days although these figures are not contextualised (e.g. the reason for prescriptions). Banerjee’s report on antipsychotics came at the end of 2009 (see here) and it would be interesting to see the figures in 2010.

Study shows association between depression and dementia – others also do although the relationship is complex http://bit.ly/bNKIXn.Percentage thickness changes in the inferior temporal and right fusiform cortices at six-months were associated with reduction in memory performance in this relatively small study (n=142) of older adults. There is a review article here on the three newly classified variants of primary progressive aphasia. A test of olfaction was used to discriminate between performance in people with Alzheimer’s Disease and Mild Cognitive Impairment (MCI) in one study. Optimal unirhinal performance did not discriminate between AD and MCI although suboptimal performance did. There is a review of treatment of sleep disturbances in Alzheimer’s Disease in the International Journal of Geriatric Psychiatry covering non-pharmacological treatments including Bright Light Therapy as well as pharmacological treatments. The authors conclude that more research is needed in this area. There is a write-up of a study which used susceptibility-based MRI to investigate differences between MCI. This imaging technique is effective for investigating the cerebral vasculature and the researchers found evidence of microhaemmorhages in people with MCI compared to a control group. Further research shows an association between adult central adiposity and later life dementia in this study of community residents (n=700). There is a literature review comparing memantine and ACHEI’s tolerability data here.

There was a small study which involved comparing post-mortem examinations of the brains of people who had Frontotemporal Lobar Degeneration (FTLD) and Alzheimer’s Disease with a control group. The researchers concluded that there was a decrease in the protein SNAP-25 in the FTLD group. The group also found that SNAP-25 levels were further decreased by the presence of the APOE4 epsilon 4 allele. The researchers in a small Positron Emission Tomography (PET) study and part of the Osaki-Tajiri project found that administration of Donepezil was associated with both an improvement in visual hallucinations in 50% of participants as well as a reduction in metabolism in the medial occipital cortex in subjects with Lewy Body Dementia. The relationship between acetylcholine and visual hallucinations in other disorders has been discussed elsewhere and it will be interesting to see further replication of this work particularly in terms of the localisation of hypometabolism.

There has been some positive news in Frontotemporal Lobar Degeneration (FTLD) research with two groups independently identifying the role of an FTLD related gene – progranulin in binding to a cell surface protein – Sortilin. There has been a recent PNAS study involving researchers from several institutions looking at the effects of Metformin on Alzheimer’s Disease associated neurofibrillary tangles in mice. The researchers found some evidence that Metformin interfered with tau phosphorylation and that it might have a prophylactic effect against the development of tangles. However it will be interesting to see the results of clinical trials. A post-mortem study examined dementia in the oldest old (90-103 years of age). The researchers correlated Clinical Dementia Rating (CDR) scores with neuropathological findings. They found that with the younger population there was a significant correlation between diagnosis of dementia and a combination of rating of severity of white matter lesions, Braak staging and presence of Beta Amyloid protein deposition. These three factors predicted only 30% of the variation in the CDR scores however.

small structural MRI study (n=68) looked at the relationship between scores on a neuropsychological test  battery (CERAD) and cerebral correlates in 60 people with Mild Cognitive Impairment, 34 people with Alzheimer’s Disease and 32 controls . The researchers found that performance on certain memory tasks (immediate and delayed recall) was significantly correlated with grey matter density in several areas rather than one suggesting these functions had cortical network correlates. The Alzheimer’s Forum have a four part series on a London conference examining research trials for autosomal dominant Alzheimer’s Disease and Huntington’s Disease. Participants at the conference were particularly interested in how drugs targetting amyloid plaques could be used prophylactically in the presymptomatic phase. There was also discussion of how biomarkers could be useful in evaluating disease progression in research trials. The report also draws attention to the Dominantly Inherited Alzheimer’s Network.

Schizophrenia


A recent relatively small study in the Archives of General Psychiatry looked at people with schizophrenia (n=8) and compared them with controls (n=8). They used structural imaging to compare the hippocampal volume after a program of aerobic exercise. There was found to be 12% increase in hippocampal volume in the people with schizophrenia and a 16% increase in the control group adding to the evidence base for the benefits of exercise in both health and illness (see also the book reviewed in this post). There is a special edition of Brain Bulletin on Schizophrenia genes freely available here. This includes papers on the complex traits of schizophrenia and genome-wide associations. Electroretinography has been used to investigate healthy people with a family history of schizophrenia or bipolar disorder and the researchers have found preliminary evidence of a reduction in the responsiveness of the rods in the retina. They compared 29 people with a family history of either Bipolar Disorder or Schizophrenia with 29 healthy controls without a family history of these disorders. They found a significant difference on one of the amplitude measures (23%)(p<0.0001). The researchers interpreted this as suggesting a possible genetic basis for an alteration in the early stages of sensory processing. However it will be interesting to see if these findings are replicated in larger studies and if so then it will complement other lines of evidence showing a relationship between altered perceptual (rather than sensory) processing in the cortex and psychopathology.

Some people with epilepsy may develop psychosis between seizures – interictal psychosis and the prevalence varies between 0 and 16% (Trimble, 1991)(Umbricht et al, 1995). In a Japanese study published in the British Journal of Psychiatry 285 people who had developed both epilepsy and interictal psychosis were assessed (Adachi et al, 2010). The researchers found that the time interval between onset of epilepsy and interictal psychosis displayed a skewed distribution (to the left i.e closer to the onset of epilepsy). The researchers were also able to better characterise the relationship between interictal psychosis and epilepsy in their sample. Thus a family history of psychosis was associated with earlier onset of interictal psychosis as were the generalised forms of epilepsy. The researchers conclude that there were independent risk factors for both epilepsy and interictal psychosis as well as possible shared risk factors.

A widely reported study (e.g see here and here) looked at a murine model of schizophrenia and the researchers provide evidence of a neural substrate for the association of chromosome 22q11 with schizophrenia. The researchers found that the deletion was associated with a disconnection between the hippocampus and the prefrontal cortex. It will be interesting to see if evidence of this disconnection is found in people with chromosome 22q11 mutations or deletions. An Indian group has conducted a randomised placebo-controlled trial of Olanzapine + Placebo v Olanzapine + Topiramate (n=72; 12/52; first-episode) in Schizophrenia showing a significant weight increase versus weight loss in the respective groups  (Narula et al, 2010). These results should be interpreted in the wider context of the considered review process needed for local guidelines. A large study in Acta Scandinavica Psychiatrica (n=1213) compared people with early and late-onset schizophrenia against controls on a number of psychometric measures (Vahia et al, 2010). The authors write that

Early-onset schizophrenia and LOS groups differed from NCs on all measures of psychopathology and functioning, and most cognitive tests

There were differences between the LOS and EOS groups and the authors concluded that Late-Onset schizophrenia should be considered as a subset of schizophrenia. An american study used a grounded theory approach to investigate the responses of 12 African-American families to treatment of a family member with psychosis. The authors identified a number of themes and concluded that

‘The findings suggest that due to fear of the official label of a mental illness, certain coping mechanisms may be adopted by families, which may result in a raised threshold for treatment initiation’

The authors recommend further research and suggest that this may influence future public education campaigns (Franz et al, 2010). There is a small case series (n=2) showing the effective use of fluvoxamine in the treatment of aripiprazole-induced akathisia perhaps warranting a randomised-controlled trial or pilot study (Furuse et al, 2010). Over at the Schizophrenia Forum, the schizophrenia gene database has just been updated with new features including methods for visualising the data. There is coverage of a study providing evidence of a relationship between the DISC-1 and NRG-1 genes both of which are associated with schizophrenia. The research also shows that DISC-1 is expressed in glial cells and the significance of this is discussed further in the article.

The researchers in a 5-year prospective  study published in the British Journal of Psychiatry examined people with schizophrenia or bipolar depression or both, with and without diabetes. For those with diabetes the hazards mortality ratio for schizophrenia was 1.84 (95% CI 1.42-2.40) and for bipolar disorder was 1.47 (95% CI 1.07-2.02). This emphasises further the importance of recognising physical and mental illness comorbidities and this has been the focus of various studies and initiatives. Studies such as these can be helpful in evaluating and influencing such initiatives. A comparison of 56 older adult marathon runners (>60 years) and an inactive control group (n=58) using a neuropsychological test battery (CERAD and Vienna neuropsychological test battery) found a significant improvement on only the five point test for the marathon group. The marathon group did not show increased BDNF levels which has been associated with exercise. However this was a cross-sectional study and a longitudinal cross-over design might offer other insights into the relationship between running and cognition in older adults. Other test components were correlated with single areas. One study examined the experience and opinions of psychiatrists on drug-drug interactions for oral antipsychotics while a large study (n=18,154) compared the incidence of adverse events for Ziprasidone and Olanzapine. Current Directions in Psychological Sciences have an open access edition focusing on Schizophrenia here while there is an open-access review of Aripiprazole in the treatment of late-onset schizophrenia here.

 

Research in Alcohol Dependence


In research into the treatment of alcohol dependence, there has been found to be a strong relationship with Corticotrophin Releasing Factor in a murine model. A number of antagonists of CRF were successful in alleviating alcohol dependence related behaviours and it will be interesting to see the results of human trials.

Research in Mood Disorders


There are preliminary reports that a proprietary combination of Buspirone and Melatonin – BCI-952 is effective in people with depression on the basis of a 6-week trial (n=142) with various outcome measures although this is a press release and it will be useful to see the study in more detail when it is formally published. The significance of this is that the combination has been shown in vivo to stimulate neurogenesis which is hypothesised to be a mechanism of antidepressant action. There is a write-up of a longitudinal study comparing women with depression who were placed on a treatment program focusing either on weight loss or weight loss and treatment of depression. The researchers found that women in the latter group had significantly more weight loss than those on the former program. There’s another paper from the Journal of Clinical Psychiatry that looks at potential future antidepressants that are in the early stages of research and from the following classes

- Serotonergic drugs

- Triple uptake inhibitors

- Glutamergic drugs

- Neurokinin based interventions

- Antiglucocorticoids

- Neurogenesis based drugs

- Nicotinic agents

Drug trials can be found at the Clinical Trials register (see here) where for example a Phase 1 trial of the neurokinin 1 receptor antagonist GSK424887 has just been completed. There is a small 6-week  study (n=54) in the Journal of Clinical Psychiatry examining the use of valproic acid in people with Bipolar Disorder I or II depression. This is a double-blind randomised placebo controlled trial with the valproic acid group associated with 38.5% v 10.7% (placebo) of subjects meeting response criteria (p=0.017 0.17). Depression was assessed using the MADRS although the difference in remission rates (rather than response criteria) has a p-value of 0.208. There is a report here on a recent study in Biological Psychiatry (see here) showing evidence of decreased time to remission of depression in a trial of Scopolamine compared to other classes of antidepressants. Scopolamine is a muscarinic antagonist and the tricyclic antidepressants also act on these receptors in contrast with the SSRI’s. There were 23 subjects in this double-blind placebo-controlled cross-over trial and there was both a statistically significant improvement (p=0.001) and clinically significant improvement (32% reduction in MADRS scores compared to 6% in the placebo in the first phase of the study.

An economic analysis of a stepped-care model of prevention of anxiety and depression in older adults showed that the incidence could be halved and a costing per depression-free year was calculated (Harm van Marwijk et al, 2010). The study was performed in the Netherlands and included older adults over the age of 75 (n=170).  The stepped care model included ‘watchful waiting, bibliotherapy, problem-solving treatment and antidepressant medication’ following a mailing of the Centre for Epidemiological Studies Depression scale (CES-D) to the patient and follow-up call. There is a write-up of a Nature Medicine study involving post-mortem whole-genome tissue scans in 21 people who had been diagnosed with depression and 18 controls and finding a 2-fold increase in the MKP-1 gene product in the brains of the depressed group. MKP-1 has associations with neuronal survival. A JAMA paper outlines details of a successful suicide reduction program in people with depression. In this population, the suicide rate was reduced by 75% and over a 2.5 year period was 0.

In the online version of the Journal of Clinical Psychiatry there’s an interesting study on factors associated with good ECT response in older adults (Oudega et al, 2010). This a naturalistic cohort study with a sample size of 81. The authors found that while white matter hyperintensities or global atrophy weren’t associated with differences in response, Medial Temporal Lobe atrophy (MTA) was. On the Montgomery Asberg Depression Scale, MTA was associated with an almost 50% reduction in response compared to those without MTA and this was significant at the 1% level. This is interesting in terms of other research suggesting an association between ECT response and an increase in hippocampal volume (as in this small study) as well as other research suggesting a role for various nerve growth factors. Nevertheless it would be good to see further replication of these findings and it would be particularly interesting to look at what happens to hippocampal volume (if anything) after treatment in a similar sample population.

Sleep

In a small study (n=18) researchers found that sleep deprivation was associated with a slowing in speech as well as a reduction in the variation of tone. There’s a write-up here of another study looking at sleep in African and Hispanic Americans (n=1107) and finding an association between sleeping either less than six hours or more than 8 hours a day and the accumulation of visceral fat. The study was published in the journal Sleep (see here) and was a longitudinal cohort study with various measurements at 5-year intervals. These findings are potentially important in view of other research showing increased mortality in groups with this amount of daily sleep compared to those who sleep between 6 and 8 hours daily. This new research is examining the pathways involved and in turn this information can be potentially useful in stratifying risk although this would require further research.

Neurotic, Stress Related and Somatoform Disorders


This is an interesting idea. One developer has produced an ‘anti-stress’ pen that detects the movement of the user’s hand and analyses this for evidence of ‘anxiety associated’ movements. The pen is able to provide feedback to the user. Breathing exercises are an effective way to manage anxiety attacks. One study (n=41) has demonstrated an advantage for feedback on carbon dioxide levels using a capnometer when compared to cognitive therapy. This is referred to as Capnometry Assisted Respiratory Training or CART for short. The researchers in a study using Magnetoencephalography looked at a group of US Veterans with Post-Traumatic Stress Disorder (PTSD)(n=74) and a group of controls without PTSD. They identified a characteristic signal in the people with PTSD using what they refer to as the ‘synchronous neural interactions test’. The distinction between this biological marker and a diagnosis of PTSD is discussed over at MindHacks. The authors of a PLOS one study examined flashbacks after presentation with distressing images. Subjects were also asked to take part in either a game of Tetris which involved visual memory or a verbal memory task. They found that those who played Tetris were less likely to experience flashbacks after presentation of the images than those engaged in verbal memory tasks. The researchers suggest that playing Tetris may be useful in preventing PTSD although the events leading to PTSD are considerably different (in the DSM-IV diagnostic criteria) from the research paradigm.

Dyslexia

In a small structural and functional imaging study researchers identified the right frontal region as an important area in differentiating between children with dyslexia associated with improvements in reading over time. This was based on both the functional and structural (diffuse tensor imaging) findings. However it will be interesting to see larger replication studies.

Personality

In the British Journal of Psychiatry, there is a systematic review of pharmacotherapy for Borderline Personality Disorder (Lieb et al, 2010). The researchers identified pharmacotherapy studies of people with a DSM-III/DSM-IIIR/DSM-IV/DSM-IV-TR diagnosis of Borderline Personality Disorder. They included studies which allowed for pooling of effect sizes and grouped the symptom clusters into interpersonal problems, impulsive-behavioural dyscontrol, cognitive-perceptual symptoms and affective dysregulation. In these four clusters, the researchers were able to find clinically and statistically significant effects for specific psychotropic medications which are outlined in the article. They note a number of limitations including the exclusion criteria in the original studies meaning that in a number of studies there may be differences from a clinical sample of people with a diagnosis of Borderline Personality Disorder. They conclude from their study that on the basis of their evidence pharmacotherapy can be directed at symptom clusters and they suggest that their findings can be of relevance to any revisions of APA and NICE guidelines.

Autistic Spectrum Disorders

The use of copy number variants in Autistic Spectrum Disorders is reported on here. There are results from a preliminary study involving the use of Oxytocin in people with Asperger Syndrome. The researchers concluded that there was evidence of increased responses to social cues including the degree of cooperativeness of other players in a ball game. However this was a small study with 13 subjects and it will be interesting to see the results of larger replication studies.

Neurophysiology

There is a write-up of an fMRI study in which volunteers were asked to respond to picture of facial expressions with words superimposed. The researchers found that the subjects would respond less quickly to the words if they were incongruous with the expressions on the faces (e.g the word sad superimposed on a happy face). The researchers also found that when this occurred there was corresponding activity in the left inferior frontal cortex and inferred that this is where inhibition of automatic responses occurred. What is interesting about their finding is that it may lead to insights in another area. Some people with schizophrenia experience what is known as incongruity of mood – they might laugh when they are feeling sad. These findings might be useful in generating a hypothesis about why this might be so.

Neuroscience

Being ‘connected’ with your image of a future self was associated with saving money for the future in one study described here. There’s a discussion of motion sickness in virtual reality settings here. In a small study it was found that the silhouette illusion – an illusion where rotatory movement is perceived – the response is not associated with handedness or personality type. In a very interesting study researchers used two-photon microscopy to observe synapse formation between neurons. Their observations led them to conclude that neurexins were integral to the process of synapse formation.

In a recent well-publicised New England Journal of Medicine study, researchers have found an has been the association of between expected brain activity with and answers to questions about familiar topics in a person with a previously clinically recognised vegetative state. There is coverage of the study here which includes a video showing the location of brain activity in the visualisation tasks in a demonstration. The original paper is here and the supplementary paper is here. This was a continuation of previous research in this area a few years ago. The researchers used fMRI with a 3T scanner in two European sites. The controls and the subjects were asked to visualise themselves hitting a tennis ball or walking from room to room in their home while visualising the scenery.

Tennis Game

These two tasks activated the supplementary motor area (SMA) (motor task) and parahippocampal gyrus (PHG) (spatial task) respectively. The researchers then asked all subjects to associate the motor task with yes and the navigation task with no. They were careful to ensure that the subjects attended to these tasks with a period of sustained attention so that the signal could be distinguished from that associated with more automatic responses. This was done in order to increase the likelihood that the activity represented ‘conscious’ activity. The tasks were repeated on 5 occasions to increase the reliability of the data after averaging the signals. They then presented subjects with autobiographical questions. I wasn’t clear on whether the questions varied from one subject to another. They were then asked to think the correct response – a yes or a no by means of the associated imagery. The researchers averaged the activity for the imagery tasks. They averaged the activity for the responses to questions. They identified the ‘centre’ of the activity for both tasks and calculated the distance of the centres of activity from each other to produce a ‘similarity’ score. The ability of a person to produce activity in the SMA or PHG in response to the researcher’s instructions was inferred as evidence of the will (although perhaps an interruption of auditory or semantic processing may interfere with task responses also). Of 54 patients in the study with a clinically recognised vegetative state, in 5 of those people activity in the appropriate areas were associated with the researchers’ instructions on the imagery tasks. However when it came to the autobiographical questions, only 1 subject produced activity associated with the correct responses. In this subject the expected activity for correct responses was identified in 4 out of 5 of the autobiographical questions.

What was interesting here was that as well as averaging group activity and comparing groups, the researchers focused on the individual results. Perhaps this was necessary as there was only one subject with the anticipated evidence of ability to respond to questions. I wasn’t clear on what the researchers’ thoughts on the ‘incorrect’ response was and which method was used for controlling for multiple comparisons (this time it’s a slightly different type of multiple comparison to that discussed in a previous paper reviewed here) as the tasks were administered to 54 subjects with the above results. It will be interesting to see further results in this area and if this approach proves successful then there may be other conditions which it might be applicable to where there are similar difficulties with communication.

Miscellaneous

Researchers recruiting subjects for clinical trials in rural areas have provided evidence that the use of specific metaphors are better than others and that the concept of randomisation can be misunderstood with some metaphors. Researchers conducted a large study on face recognition which provided evidence that face recognition peaks at between 30 and 34 years of age. Professor Richard Williams, is interviewed in this article and discusses some of the effects that the earthquake might have on children in Haiti and approaches to responding to this. The Psychiatric Bulletin familiar to British Psychiatrists has been renamed ‘The Psychiatrist’ and includes articles submitted by allied mental health professionals. There are 2 interesting articles on the recovery model as well as a meta-analysis of low and high-dose quetiapine. The latter article looks includes two studies (combined n=175) and concludes from the evidence that low and high dose quetiapine show equal efficacy in schizophrenia on outcome measures including positive symptom score on the Brief Psychiatric Rating Scale although these were 6-week trials  (Painuly, 2010). There is another interesting article by a nurse and psychologist team reviewing the standard community mental healthcare for people with severe personality disorder. The researchers were interested in the standard management against which other treatments were compared and conclude by recommending further empirical evidence for the standard approach (Koekkoek et al, 2010).

There is a very interesting article in ‘The Psychiatrist’ about the identity of psychiatrists or more specifically the areas of core expertise (Craddock et al, 2010). Craddock and colleagues propose 9 core attributes of the psychiatrist which include a broad biopsychosocial perspective, using a broad knowledge of biology and ‘clinically relevant aspects of neuroscience’ as well as advocating for people with a mental illness. In a small, preliminary study (n=9) looking at the use of blueberry juice on memory there was a significant improvement on a test of paired associative learning and word list recall at 12-weeks in older adults with ‘early memory changes’. However this will need to be replicated preferably over a longer time period and in a well characterised and larger population with randomisation, blinding and a control group. While blueberries are noted to have strong antioxidant properties, the authors suggest that it is the properties of the anthocyanins in blueberries which influences neuronal signalling which may relate to any beneficial effects.  A development in electron microscopy is the use of electron cryotomography. This is the rapid freezing of biological materials to -140 degrees Celsius to preserve the positions of intracellular structures. This article looks at a study published in the Journal of Cell Biology using this technique. The authors note that filaments in the neuron constrain the activity of intracellular vesicles which contain neurotransmitters for release for example. This article looks at a study which investigated the effects of other people with varying degrees of self-control on a person’s own self-control in a variety of experimental scenarios. In these scenarios the researchers found evidence that finding evidence of self-control in others or thinking of those with ‘high’ self-control was associated with a higher degree of self-control in the subject.

There are further preliminary results on vascular decompression in Multiple Sclerosis and it will be interesting to see the results of further research in this area. The use of neuroscience in court cases was discussed at the annual meeting of the American Association for the Advancement of Science and a mock trial was staged and the associated complexities explored. A neurosurgeon commenting in the Journal of the American Medical Association has called for helmets to be used in skiing and snowboarding which to reduce the risk of head injuries in accidents. The authors of a Nature Neuroscience paper have found evidence that A-Type K+ channels and T-Type Ca Channels act together during action potential transmission. An fMRI study provided evidence of different regions involved in learning new verbs (left posterior temporal gyrus and left inferior frontal gyrus) and nouns (left fusiform gyrus) as well as a relationship between hippocampal activity and the efficiency of learning new nouns. This information could be of relevance to a number of conditions which involve disorders of language and memory. For more information on the study see here. A study involving neural prosthetic devices in people provided evidence of the function of the beta and delta oscillations identified in the EEG. Based on their findings about the timing of the oscillations, the researchers concluded that the beta oscillations were strongly associated with anticipating commands for initiating movements. For more information see here. Discover reports on some experimental evidence to suggest that smells and sounds are perceived together as hybrid ‘smounds’ – at least in a murine model. These conclusions are based on the activity of cells in the olfactory tubercle which respond not only to smells but also auditory tones presented alone or in combination with smells*.

There was a recent study (also covered here) in rats which found that suppression of Vasopressin secretion interfered with the ability of adult rats to recognise baby rats. This adds to other research from the same research group which suggests that Vasopressin may be involved in the formation of emotional memories which are important for social interactions. If this is replicated in humans then it would have application in social cognition which in turn is relevant to a number of conditions. In another widely reported study, a team have collected intestinal bacteria from a sample of 124 European subjects and sequenced the genomes of the 160 bacteria identified. The resulting genomes when combined into a ‘metagenome’ are larger than the human genome and the significance of this for human illnesses will surely become clearer with time. There is a fascinating look at a study investigating how ‘fast food’ may generate psychological responses that modify behaviour at ‘We’re Only Human’. The subjects in the study were asked to look at a computer screen and solve a task while very rapid images of fast-food related symbols were flashed up in the periphery. When these symbols were presented (priming) the subjects would respond more rapidly and this was interpreted as they were feeling ‘time pressure where there was none’. There were additional stages in the experiment. When subjects were primed with the fast food symbols they would select more efficient household item designs e.g a four-slice toaster rather than a two-slice toaster.

Finally the subjects primed with the fast food symbols were more likely to accept a small amount of money in the present rather than delay acceptance of a larger amount of money. So the term ‘fast-food culture’ takes on a new meaning.

Wray Herbert looks at a new paper in which psychologist Ibrahim Senay investigated wilfulness and willingness. He used an anagram paradigm:-

But before starting this task, half the volunteers were told to contemplate whether they would work on anagrams, while the others thought about the fact that they would be doing anagrams

The subjects who considered whether they would work on the anagrams completed more anagrams than the other group. The experiment was altered slightly and subjects wrote one of two phrases

Some wrote the words I Will over and over, while others wrote Will I

Again, the group that wrote ‘Will I’ completed more anagrams. The same results occurred when applied to exercise. The subjects were more likely to experience guilt if they willed themselves to complete the anagrams in contrast with those who questioned whether they would. Senay interpreted the latter group as being intrinsically motivated. So if these results generalise, this would suggest that questioning whether to engage in a task will be more effective than goal setting although it would be interesting to see further results in this important area.

Aaron Saenz covers a recent study on facial recognition in twins utilising a number of relevant tasks one of which is demonstrated in the article. The findings showed a 0.7 correlation of scores in identical twins compared to a 0.29 correlation in non-identical twins and thus support a strong genetic component for facial recognition. Dr Grohol tackles the recent New York Times article on psychiatry and draws his own conclusions. The Neurocritic refers to a paper by Carl Friston relating his concept of free energy to a number of Freud’s concepts in a recent paper he has published. Sandy Gautam looks at a remarkable paper on the C.Elegans nematode in which the researchers are able to predict 95% of the variance in the shape of the worm using a simple model. While people are many orders of magnitude more complex than C.Elegans it is a useful proof of principle and suggests that perhaps much further down the road a predictive model of human movement based on neural pathways and physiology may be feasible (there are many developments in this area already particulary in the area of neural prosthetics) which would have applications in a number of conditions. Karen Sternheimer analyses a recent meta-analysis that examines the relationship between violence in video games and aggression in children and gives her justifications for rejecting the author’s conclusions.

In a widely reported BMJ study, the use of checklists – care bundles – for 56 conditions was associated with a marked reduction in mortality rates at a North London NHS Trust. There is coverage of a paper here which suggests that linking Electronic Healthcare Records with DNA databases can accelerate the identification of relationships between genes and disease. The UK government has set aside an extra £2 million for funding mental health services for war veterans to be allocated to a range of services including community psychiatric nurses, GP training and helplines. A widely reported neuroimaging study provided evidence of frontal cortex activity being divided between hemispheres for two tasks compared to one. Additionally the authors concluded that there was a deterioration in allocation of resources for more than two tasks. A small PET study shows evidence of hypometabolism in the Superior Temporal Gyrus in people with Temporal Lobe Epilepsy (TLE) with deja vu compared to healthy controls and people with TLE without deja vu. The authors of a paper in the open access journal Trials look at unpublished Stroke trial data which if published has the potential to influence practice. The insertion of artificially-synthesised DNA into a bacterial cell with subsequent establishment of viability has been widely reported in the media (see here, here, here, here and here) and will lead to substantial debate about the ethical implications as well as leading to a vast array of applications. An interesting soundbite from Venter’s presentation is

This is the first self-replicating species that we’ve had on the planet whose parent is a computer

One group has identified details of Lithium mediated anti-inflammatory pathways which may contribute to an understanding of Lithium’s mechanism(s) of action. The authors of this study have called for psychiatrists to be included in ‘disaster first-response’ teams on the basis of their findings. A group of physicists have predicted that the magnetic fields associated with ball lightning would be sufficient to stimulate phosphenes, visual experiences secondary to cortical activation which would likely influence the perception of lightning. Also an ambitious scientist is attempting to detail the wiring of the brain in what is referred to as the connectome project.  There is a write-up of a Nature paper in which a research group demonstrated a change in Blood Brain Barrier permeability using pharmacological modification of pericytes. A merger between the National Prescribing Centre and the National Institute for Clinical Excellence is taking place and scheduled to complete by April 2011. The National Prescribing Centre informs Government on the economic implications of medication prescribing. There is a link to an interesting BPS article on ‘scientific discounting cognitions’ at this week’s Spike Activity at Mind Hacks. The article features a discussion with Professor Munro who has found that a person’s reception to new findings in science is influenced by their underlying values and the details are explored further in the article.

Ed Yong has an ‘missing links‘ article with interesting general science links and draws the readers attention to recent results from the 1000 Genomes Projection Consortium. There are more details on this at Nature and just to quote from the abstract

On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders

and also

‘From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10−8 per base pair per generation’

This first figures are really interesting. If we can generalise from this data to the wider population that we would each have about 300 genes that aren’t functioning (I wasn’t clear on whether these are inherited or if they are de novo mutations).  Since mutations are the mechanism through which we become genetically differentiated, each mutation can produce a change which can lead to successful adaptations to the environment. Switching off a gene here or altering a gene there might in some way give a person a selective advantage that better enables them to pass on their genes. On the other hand there were an average of 50-100 genes that have been associated with ‘inherited disorders’. At the moment, the genome sequencing technology is not widely available and people might learn of an inherited disorder after clinical suspicion is raised and appropriate investigations are undertaken. However this technology will be widely available in 10 years time and we have to look realistically at the possibility that clinical practice will be transformed. Thus in ten years time, the general population might go to private companies to have their genomes sequenced, receive the results and then present to their doctors with a list of 50-100 variants asking for advice. This would have implications for primary and secondary care that will need to deal with both realistic and unrealistic expectations.

One paper that has been widely reported in the media (see here, here and here)  is the use of transcranial magnetic stimulation in a group of students which was associated with improvements in performance on mathematics tasks. The paper is freely available here. This looks like a pilot study as the sample size is small (n=15). Five students were adminstered a current in one direction across a region including the parietal lobe, another group received the current in the reverse direction and a third group acted as controls receiving a small current which was considered to have no effect. There were 3 tasks involving learning the value of symbols which must be discriminated according to magnitude, discriminating symbols according to size and mapping symbols to physical space. There were six training sessions over 7 days and the stimulation was applied during the course of the training session. There were clear and significant advantages for one treatment group over the controls in the symbol learning task but in the other tasks the results were complex and different learning effects were described in all three groups. The researchers have generated a clear hypothesis which has been reported widely in the media and it would be interesting to test this specific hypothesis with ‘real-world’ examples in a larger sample sufficiently powered to investigate the effects of age.

The researchers in a french study drew a number of conclusions about the ‘Activities of Daily Living Scale’ and suggested areas for improvement. The authors of a recent study looked at participants who had enrolled in a research register. They found that for older adult participants, transport was the biggest barrier to participating in the research.There is a write-up here of a study involving participants in their 20′s, 40′s and 60′s. The researchers found evidence that the older adult group were better at reappraising negative events positively but that the other two groups scored more highly on tasks that involved ‘detached appraisal’ in which events are viewed while dissociating feelings. Evidence for efficacy of tool that measures pain in non-verbal population – (open access) http://bit.ly/cTFLi7. A lady with panic disorder is reported to have spent 4 months in a hospital car park highlighting the morbidity that can be associated with this disorder. Slowed reading speed found with an e-reader v printed book in one study http://bit.ly/9VEf1H. There’s a write-up of some recent research which provides evidence that neurons form local and global networks through synchronous firing. There’s a write-up of another interesting study here in which the researchers provided evidence that career choice is associated with the brain region that undergoes atrophy in people with fronto-temporal lobar degeneration. The inference is that career choice will determine the nature of the work that is undertaken which in turn will determine the brain region which is regularly used although this relationship is unlikely to be straightforward. An fMRI study in 33 volunteers provided evidence that reduced activity in the dorsal striatum (associated with reward) in response to drinking a milkshake was associated with weight gain at six-month follow-up and the researchers hypothesise that overeating is associated with reduced pleasure from eating. In a study investigating volition, stimulating the left side of the brain with transcranial magnetic stimulation in 33 volunteers was more likely to lead to them ‘choosing’ to use their left hand in choice tasks.

Psychiatry 2.0

The Frontier Psychiatrist has a very interesting interview with psychiatrist Dr Iain McGilchrist. Over at Psychotherapy Brown Bag there is a very interesting article on the relationship between experience and efficacy in psychotherapy. Professor Dunbar, who coined the Dunbar number has been looking at Facebook relationships. The Dunbar number – 150 – indicates roughly how many relationships people can manage effectively. Professor Dunbar followed up his earlier work by looking at Facebook and has suggested on the basis of his analysis that there is evidence that this number remains. Even when people have higher numbers of friends, they effectively manage the core group of about 150. He also found some gender differences in relationship maintenance. The Hawaii Medical Association is now offering patients virtual appointments with doctors and this will no doubt be followed with interest by other organisations. An american study looked at census data between the years 1990 and 2006 in the state of Virginia and concluded that socioeconomic status was strongly inversely associated with mortality and that if the mortality rates of the 5 most affluent states and cities were applicable throughout the state there would be a 25% reduction in mortality.

DSM-V

The draft changes for DSM-V have been published by the American Psychiatric Association Draft Development Team for DSM-V here. I might have overlooked something but it looks as though it is an overview of the changes being suggested for specific conditions that are being presented.

Dementia Reclassification?

Firstly I was interested in what amounts to a wholescale reclassification of the dementias and related conditions into major and minor neurocognitive disorders. There are some nice ideas contained within this move including the consideration that it is not only memory which needs to be affected. However I was unclear on reading the descriptions of whether it would include the subtypes as I could find no mention of this. However it would be unusual if the various subtypes of dementia for which there is an abundance of evidence were not included as subtypes within this framework as this could be considered a step backward. Additionally I couldn’t find any mention of the term Mild Cognitive Impairment (although there are some broad similarities with minor neurocognitive disorder) and the various subtypes for which there is an emerging evidence base and which is the focus of research in the hope that a better understanding could lead to prevention or amelioration of subsequent dementia.

Mental Disorders Due to a General Medical Condition

There were very few changes here. One suggestion was to use a catatonia specified elsewhere instead of catatonia secondary to a medical disorder.

Personality Disorders

There are some big changes in the Personality Disorders. These have been reduced from 10 to 5. One of the difficulties with the current Personality Disorder types is the diagnostic overlap. A person may fulfill the criteria for more than one type of personality disorder. There are a number of changes to the criteria which should improve reduce the number of comorbid personality disorder diagnoses. A simple likert-scale is used for quantifying personality and personality traits and the five types are Borderline Personality Disorder, Antisocial/Psychopathic Type, Avoidant Type, Obsessive-Compulsive Type and Schizotypal Type.

Substance-Related Disorders

There are a large number of new diagnostic labels being considered for inclusion and subsuming current labels. For instance alcohol dependence syndrome may be subsumed under alcohol-use disorder. Cannabis withdrawal is another diagnosis being introduced. The discussions around the terms ‘addiction’ and ‘dependence’ are discussed below.

Schizophrenia and Other Psychotic Disorders

There are big changes to the diagnosis of Schizophrenia with a proposal for removing subtypes including paranoid schizophrenia, disorganised and catatonic schizophrenia. Changes are being suggested in order to bring DSM-V into closer alignment with ICD-10. Proposed changes to the criteria for Schizoaffective Disorder are meant to increase reliability. ‘Psychosis Risk Syndrome‘ is being introduced (see further discussion below) and a Catatonia Specifier is being suggested. This is apparently because catatonia is ‘often not recognised’.

Mood Disorders

Mixed anxiety and depression disorder is being introduced with criteria that avoid ambiguity. This is currently included in the appendix of DSM-IV. There is a proposal to rename Dysthymic Disorder as chronic depressive disorder. There is a proposal to replace Bipolar Disorder Most Recent Episode Mixed with a mixed specifier. There are a number of changes in the criteria of Manic Episode particularly around energy levels.

Anxiety Disorders

The proposal is to include Obsessive-Compulsive Disorder under a new category of ‘Anxiety and Obsessive-Compulsive Spectrum Disorders’. The changes here are further discussed in the ‘PsychBrownBag’ Blog and the ‘OCD Center of Los Angeles’ Blog below.

Somatoform Disorders

There is a proposed amalgamation of four conditions into ‘Complex Somatic Symptom Disorder‘ but for further discussion see the ‘OCD Center of Los Angeles’ Blog below.

Factitious Disorders

The proposal is to reclassify Factitious Disorders under Somatic Symptom Disorders.

Dissociative Disorders

Theere is a proposal to subsume Dissociative Fugue under Disssociative Amnesia. Similarly there is a proposal to remove Dissociative Trance Disorder and integrate the criteria into the diagnosis of Dissociative Identity Disorder which has a number of other proposed changes.

Sexual and Gender Identity Disorders

There are a number of new diagnoses.

Eating Disorders

A new diagnosis of Binge-Eating Disorder is recommended (for further discussion see below). In Anorexia Nervosa there is the proposal to remove the criterion of amenorrhoea whilst in Bulimia Nervosa there are some proposed changes to the frequency of binge eating episodes and the purging criteria.

Sleep Disorders

There are a number of new conditiosns (a number of which subsume other conditions) including Klein-Levin Syndrome, Primary Central Sleep Apnoea, Primary Alveolar Hypoventilation, Rapid Eye Movement Behaviour Disorder and Restless Leg Syndrome amongst others. There are a number of changes to the criteria for narcolepsy including hypocretin deficiency.

Childhood disorders

There are a large number of suggested changes including the removal of Rett’s Disorder, a number of proposed changes to the Attention Deficit and Hyperactivity Disorder criteria, the inclusion of Post-Traumatic Stress Disorder in school age children and Temper Dysregulation Disorder with Dysphoria which is further discussed below. Interestingly the wording for Separation-Anxiety Disorder may be changed so that it can be used with adults also. This is because there is evidence for an adult separation-anxiety disorder.

Impulse Control Disorders Not Elsewhere Classified

There is a proposal to include Pathological Gambling with substance-related disorders. There are proposed changes for Trichotillomania further discussed below.

Adjustment Disorders

There is a proposal to move Adjustment Disorder to a grouping of Trauma and Stress-Related Conditions.

Discussion of the Draft DSM-V Changes Elsewhere in the Media

Links to some of the discussions elsewhere in the media are given below.

General

The Time article looks at a number of proposed changes for DSM-V which includes the criteria for making a diagnosis of depression,use of a continuum and the case for autistic spectrum disorders, the possible grouping of non-dependence inducing substances together with dependence inducing substances in the addiction and related disorders, reducing the number of personality disorder types and making some amendments to some of the sexual disorders. Over at PsychCentral, Dr Grohol looks at a number of features of the DSM-V draft. He is encouraging of the inclusion of Binge Eating Disorder, but is critical of the criteria used in minor neurocognitive disorder, behavioural addictions and also temper dysregulation disorder whcih has a narrow time period fo 6 to 10 years for diagnosis. Over at the ‘Psyche Brown Bag‘ blog, Joyce Anestis comments on the restructuring of the multiaxial system as well as the arrival of a number of new disorders including ‘hoarding disorder’, ‘olfactory reference syndrome’, ‘skin picking disorder’ and ‘psychosis risk syndrome’ amongst others and is also confused by the proposed changes to the personality disorders. The Times has a look at a number of the proposed changes including ‘sluggish cognitive tempo disorder’. Web MD has an article on the changes and features an interview with Dr First who is critical of the utility of the diagnosis of ‘Psychotic Risk Syndrome’.

Dr Dan Carlat has a discussion of the proposed criteria on his blog and seems fairly positive on these (however I would just add that there are neurobiological criteria for a number of disorders in DSM-IV/DSM-V draft e.g hypocretin deficiency in narcolepsy above). He notes that temper dysregulation disorder is being favoured as it would avoid a diagnosis of bipolar disorder in children in a number of cases. He’s in favour the use of addiction in place of dependence or abuse and also the use of the concept of binge-eating disorder. The New York Times has a piece featuring interviews with several psychiatrists and 230 comments at the time of writing. Integral Options cafe has links to a number of posts including those on the NPR site. An article at the NPR website examines the limits of the checklist approach and how severity might be measured when using a dimensional approach. The Economist has a piece on the history of the diagnostic criteria but also cover some of the disputes that have taken place. ‘DSM-V and ICD-11 watch’ have some interesting links as well as a brief look at suggestions for medically unexplained symptoms. Dr Finnerty has an overview of proposed changes as well as some useful links. Mind Hacks has coverage here and here. The APA have a facebook site that interested readers can join.

‘Addictions’

Stanton Peele covers the proposed use of the term addictions in this ‘The Huffington Post’ article.  The ‘Join Together‘ website features an interview with Dr Charles O’Brien who is chair of the APA’s DSM substances related disorders workgroup. He explains the distinction between dependence and addiction and the consideration of including the term addiction in DSM-V. They also discuss the possibility of collecting behavioural addictions together with alcohol and other drug related disorders.

Anxiety Disorders and OCD

Tom Corboy director of the ‘OCD Center of Los Angeles’ writes about a number of proposed changes over at the ‘OCD Center of Los Angeles’ blog. Thus Corboy discusses the suggested use of an ‘Anxiety and Obsessive Compulsive Disorder Spectrum’. Corboy is also critical of the suggestion of agaraphobia without panic disorder, in favour of moving Body Dysmorphic Disorder into the ‘Anxiety and Obsessive Compulsive Disorder Spectrum’ and adding a muscle dysmorphia variant, critical of the aggregation of 4 somatoform disorders including hypochondriasis, in favour of the relabelling of trichotillomania as ‘hair pulling disorder’ and also for the inclusion of skin picking disorder.

Intellectual Disability

Over at the blog ‘Mental Incompetence and the Death Penalty‘ there is a guest post by Dr Watson. He criticises the proposed criteria for intellectual disability on the basis that there doesnt appear to be a consideration of the standard error for IQ testing meaning that there is what he describes as a ‘bright light’ cut-off point of 70 or below whereas in practice there is a group that are scored over 70 who would still be included amongst a number of criticisms.

Bipolar Disorder in Children

Over at the NPR website, there is a wider discussion of the diagnosis of bipolar disorder in children as well as the more recent ‘temper dysregulation disorder’.

Autistic Spectrum Disorders

The Left-Brain Right-Brain blog compares the criteria in DSM-IV with those in DSM-V for autistic disorder and autistic spectrum disorders respectively and links to a number of other articles on the subject. There is another discussion of the autistic spectrum disorders proposition here. There is further coverage here and here.

Eating Disorders

Time has a piece on orthorexia which hasn’t made it into the draft version of DSM-V. There is also coverage of the proposed changes at the Ed-Bites blog (with 15 comments at the time of writing).


Dr Dan Carlat takes a further look at the DSM-V draft proposals here. Dr Charles Parker has further coverage here and also over at the Corpus Callosum blog. There is a look at grief in the draft DSM-V proposals at Psychotherapy Brown Bag.

Evolutionary Psychiatry/Human Evolution/Origins of Civilisation/Cultural History

In an podcast/article at the Guardian there is a look at a new book looking at the inner lives of animals. There is a brief description of tree snagging – the tendency of orang-utans to jump from a falling tree at the last moment which has been likened to ‘thrill-seeking’. Colin Blakemore argues in this piece that the human brain increased in volume dramatically as a result of a new mutation at around the time of mitochondrial Eve 200,000 years ago rather than through gradual cumulative culture-associated changes. In another proposal Professor Bruce Yankner speculates that an increase in energy utilisation by the human brain could explain why humans are susceptible to Alzheimer’s Disease which is not identified in other species (even those with large brains). While not directly related to mental illness but instead to models of human evolution, the Laetoli footprints have been analysed and in this paper the authors state that they are the earliest evidence of hominid bipedalism (3.6 million years ago). There are theories that suggest that bipedalism was accompanied by adaptive cognitive changes. There is an interesting piece on cultural transmission in chimpanzees at the primate diaries here. Determining ape evolution from environmental clues secondary to antelope teeth wear patterns 8 million years ago. 58,000 year old glue and colour production in Southern Africa is discussed here. Fossil evidence suggests that fish and crocodiles feature in diet of Homo Erectus ancestors. The earliest British Neanderthal artefacts dated to 100,00 years ago although controversial but later being predated by an Essex finding.

Historian’s analysis suggests Plato used musical code to signify important parts of his text http://bit.ly/95io47. Mitochondrial analysis and the peopling of North America is discussed here http://bit.ly/97Wm8M. Computer deciphers ancient language in a few hours http://bit.ly/aL81Wy. There is evidence that multicellular life began 2.1 billion years ago http://bit.ly/cU6wzt. Fast adaptation to the environment in Tibetans provoked a lot of media interest and is covered here http://bit.ly/9ZlGAK. There is a Discovery piece on Neanderthal teeth dating study http://bit.ly/apkTeW. Music has a strong relationship to language and recent research covered here highlights the close relationship between the two. This relationship has a number of possible implications in a wide number of areas which involve language. A recent study (from a few months back) looked at music appreciation in cotton-top tamarins (a form of New World monkey) and the researchers found that they were responsive to music written specifically for them but not to human music. The music can be heard at the link above and was based on the tamarin’s own calls and other vocalisations. For anyone curious about what cotton-top tamarins look like, I’ve made two short videos (here and here). One of the factors that influences evolution is culture. There is a subtle but intriguing insight into a phenomenon which influences environmental pressures. In this article on Primatology.Net, there is a look at how cultural practices influence the interactions between humans and local macaques in Sulawi Sulawesi.

There was a study at Twycross zoo showing evidence that Orang-Utan gestures may signal intention http://bit.ly/dBpoMi. The discovery of a 3.6 my old A Afarensis partial skeleton produced a lot of discussion http://bit.ly/bSgmdI. A computer simulation and teeth analysis suggest Neanderthal/human divergence 1/2 million years earlier http://bit.ly/dk7elI. Orang utan learning to swim is covered here http://bit.ly/aNbYp5. Chimpanzees engage in territorial warfare http://bit.ly/bwcf04. A possible new hominin species has been discovered and the findings reported in the journal Nature. A finger bone was found in Siberia and an analysis of the mitochondrial DNA was undertaken. There is a suggestion that this species would have lived 30,000 years ago and could have coexisted with humans, neanderthals and Homo Floresiensi. There is detailed coverage in this article and a critical perspective is given here. If the above is confirmed by further analysis then it has been suggested that there were multiple waves of migration out of Africa rather than the two classically described. The relationship to mental illness is more tenuous as these findings are relevant to generic models of human evolution e.g adaptation to cohabitation with a competing hominin species which in turn can be used to interpret illness. A finding of general interest for human evolution is the skeleton of a child in a cave in South Africa which has been named as a new species – Australopithecus Sediba and is estimated to have lived between 1.78 to 1.95 million years ago . Although there is suggestion that this species may be intermediate between Austrolopithecus  and Homo Sapiens, critics have argued that further work remains to be done to examine a number of standard morphological features before conclusions can be drawn.

In a widely reported study (see here, here and here) presented at the American Association of Physical Anthropologists, researchers looked at regions of DNA in the genomes of 1983 people from Europe, Asia, Africa, the Americas and Oceania. These regions are known as microsatellite regions and vary between populations. By looking at the degree of variation, the researchers were able to produce a corresponding evolutionary timeline factoring in variables such as estimated mutation rates. The researchers predicted two time periods during which interbreeding with another species was necessary to account for their findings. These periods were 55,000 years ago for the Eastern Mediterranean and 45,000 years ago for Eastern Asia. The candidates for interbreeding include Homo Neanderthalensis and Homo Floresiensis. Such interbreeding could potentially explain the recent finding of a possibly previously unknown hominin – Denisova hominin – found in Siberia. The estimated periods of interbreeding also correspond approximately to the finding of pigmentation on clam-shells in Spain which are thought to have been used as body paint by Neanderthals. Needless to say if these findings are confirmed by a soon-to-be complete analysis of the Neanderthal genome then they would have wide ranging implications. The period of approximately 60,000 years ago corresponds to the lower limit of a hypothesised bottleneck of human evolution in which the human population may have been on the verge of extinction with only a few thousand members although this is a controversial hypothesis.

Team undertaking 3-d analysis of 1.5 million year old footprints probably Homo Erectus. A 2nd 4000 year old figurine from the Orkneys was discovered while 200,000 year old stone ‘knives’ were found in Israel. An extinct but interesting monkey species found in underwater carribean dive. A Wooden henge near stonehenge was a big discovery. A new theory of human evolution involving caring relationship for other species is discussed here. Google funds a 1 year project to open out ancient texts online. There is more on an important fossil primate find here http://bit.ly/9dc1tK. Gorillas playing tag? http://bit.ly/cSEn5c. There has been a lot of media coverage of the recent finding of stone tools suggesting that a human ancestor was present in Norfolk approximately 800,000 years ago. This raises all sorts of questions. For instance, if the environment was similar to present day Scandinavia then how would they survive without clothing? If they did use clothing that would be fairly significant as this is nearly 1 million years ago and would force a reappraisal of milestones in development of human intelligence. There is a video interview with the archaeologists here http://bit.ly/dC3IOg. John Hawks looks at the recent suggestion that the Neanderthal had very powerful musculature and challenges some of the assumptions about hormones by referring to the recently sequenced Neanderthal genome. At the Primatology blog there is a great article on whether animals keep pets. There is a discussion of a paper on personality in non-human primates here. Was Leonardo Da Vinci the pioneer of palaentology? http://bit.ly/d1jPjC … no – he was preceded by Mayans by 1000 years! http://bit.ly/bSvtH8.

A reinterpretation of Mesoamerican civilisation is being brought about by the finding that while Mesoamericans were producing rubber 3600 years ago  they had developed further chemical processes to refine the rubber at this time. They used the rubber in shoes among other applications. There is also an ongoing debate about Ardi (13) – the ‘find of the century’ – around the issue of whether he was more man than ape and whether he was living in woodland or savannah. There is good coverage here. One of the current questions in recent evolution is whether Neanderthals contributed to the human gene pool which would have many implications. A recent radiocarbon dating of a site in Portugal revises the date of the last Neanderthal remains to 37,000 years ago. This is significant in terms of the evaluation of a 30,000 year-old child’s skeleton which has properties of both Neanderthals and humans. In a recent study, Chimpanzees and Bonobos were compared on food tasks. The Chimpanzee infants performed differently to the Bonobos on tasks which involved identifying where food was located. The Bonobos were described as delayed in development relative to the Chimpanzees. Chimpanzees are more closely related to humans than Bonobos as Chimpanzees and Bonobos diverged some 1.3 million years ago. Slightly off-topic but the remains of a 7000-year old amputee in France shows evidence of surgical amputation without subsequent infection.

A structural imaging study published in Nature Neuroscience replicated findings in other primates – that the size of the Amygdala correlated with the number of people in a person’s social network. So now we have some convincing evidence that the Amygdala is playing an important role in social networking and it will be interesting to see how models of social functioning incorporate these findings. Chimpanzees in the wild have been observed carrying around sticks until they have offspring. The researchers inferred that they were treating the sticks as a human child would treat a doll and then argued that gender specific roles have a strong evolutionary basis. Shopping is reframed as foraging in evolutionary terms and discussed in this article. Australian aboriginal cave artwork has been found to contain living material in the form of fungus and bacteria and it is thought that this would have replaced the original pigmentation and would account for the difficulties in dating the artwork.

An interesting finding has been the interpretation of a 50,000 year-old Neanderthal clam shall which contains remnants of yellow and red pigmentation together with a black mineral substance. The researchers have concluded that this pigmentation was being used as make-up. Since humans did not arrive in Europe till much later, it was concluded that this is evidence of a Neanderthal culture and this adds to other evidence about Neanderthal intelligence (see here also). This also raises possible questions about the transformation of human art on entering Europe. The most interesting question however is whether Neanderthals are part of our genetic heritage and that question will hopefully be answered with the sequencing of specimens of the Neanderthal genome. The recent sequencing of the Chimpanzee y chromosome suggests that chimpanzees have between one-third and one-half of the genes in the human genome and that the y chromsome has undergone rapid changes relative to the other chromosomes which have been sequenced in both humans and chimpanzees. This should have implications for the kind of inferences we can draw.

While not directly related to humans, this news article involves an interview with a researcher and looks at the ‘evolution’ of stray dogs in russia. The dogs have to adapt to urban conditions. It does raise the question of how much urbanisation impacts on evolution although the selective pressures on dogs will be significantly different from people in these environments (it was interesting to see that the dogs have learnt to ride on the underground!). A mathematical model has been constructed to investigate the coevolution of the hands and feet in humans basing some of the assumptions on measurements in the humans and chimpanzees. The model supports the hypothesis that changes in the feet could affect the shape of the hands (and vice versa) and is interesting in view of the recent publication of the Ardi find (the authors of the Ardi publications took 17 years to prepare the material before publication!) a distant human ancestor which moved through the trees as well as walking upright.

There is an interesting write-up on a recent hypothesis by Professor Wheeler that cooking food may have led to an increase in brain size. The essence of the argument is that cooking reduces the amount of energy needed to digest food. In moving from Austrolopithecus to Homo Erectus and Homo Habilis there was a reduction in the size of the intestines and an increase in brain volume. The argument is that these anatomical changes were causally related to corresponding behavioural changes which enabled a significantly higher proportion of the body’s resources (i.e energy) to be allocated to the brain. Indeed this has been the subject of a Horizon programme which is available for a limited time here. There’s another interesting write-up, this time of a conference examining the ‘Origins of Human Uniqueness and Behavioural Modernity’. Discussion took place around a number of subjects including the possible role of gifts and adornements particularly in the role of signalling social status. The Primatology blog has a look at a recent study on the length of Macaque ‘conversations’.

Johan Lehrer has written a piece on evolutionary psychiatry – ‘The Upside of Depression‘ (the full article is in the New York Times here) and which has produced a lot of debate. In the article, Lehrer explains the analytic-rumination theory which suggests that depression may have an adaptive advantage associated with improved performance on ‘intelligence tests’. However there are a number of difficulties with this. For instance with depression, clinicians can see a deterioration in cognitive performance and problems with memory and concentration are two of the diagnostic criteria for depression. Here is one study for instance that shows significant impairment on cognitive tasks in people with depression compared to a control group.  There are other complications however. For instance depression can manifest differently and has multiple aetiologies meaning that it is a heterogenous disorder. As such, any successful theory is likely to explain only a proportion of cases. Clinical depression as distinct from normal sadness is associated with impairment in a number of domains and can be associated with considerable distress. On the one hand, it is encouraging that a model for depression is being discussed in a wider forum as models of illness are extremely important in generating an understanding and moving towards improved treatments. Indeed the interest raised has moved the discussion of this model forwards very quickly. On the other hand any discussion should be tackled sensitively as there are many people with depression (and their families) who have experienced significant suffering as a result of their illness. The key to this debate is in understanding that it is several steps removed from decisions about treatment. If there are any conclusions that would influence treatment then the relevant studies would need to be undertaken in order to move from speculation to evidence-based decision making. The debate has moved forwards with several people responding. For instance Dr Ronald Pies responds here and here, with Lehrer responding here. There is also another perspective over at neuron culture here.

Appendices

Appendix 1 – References

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Craddock N et al. Core Experise of the Psychiatrist. The Psychiatrist. November 10. Vol 34. Issue 11. pp457-459. 2010.

Franz L, Carter T, Leiner AS, Bergner E, Thompson NJ, Compton MT. Early Interv Psychiatry. 2010 Feb;4(1):47-56. Stigma and treatment delay in first-episode psychosis: a grounded theory study.

Furuse T, Hashimoto K. Ann Gen Psychiatry. 2010 Mar 6;9(1):11. [Epub ahead of print]. Fluvoxamine for aripiprazole-associated akathisia in patients with schizophrenia: a potential role of sigma-1 receptors.

Gauthier S, Juby A, Dalziel W, Réhel B, Schecter R. Curr Med Res Opin. 2010 Mar 15. [Epub ahead of print]. Effects of rivastigmine on common symptomatology of Alzheimer’s disease (EXPLORE).

Harm van Marwijk et al. Cost-effectiveness of a stepped care intervention to prevent depression and anxiety in late life: randomised trial. The British Journal of Psychiatry. 2010. 196. 319-325.

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Appendix 2 – Open Access Resources

Appendix 3 – Miscellaneous Resources


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