In September 2009, there was a review of an article on the construction of a diagnosis which is topical given the pending DSM-V and ICD-11. There were also reviews on the Delusional Misidentification Syndromes and one of Winnicott’s articles – on primitive emotional development. There were reviews of a number of articles on both delirium and dementia as well as a review of articles on the impact of technology on healthcare. The last of Betts podcasts on Jungian Analytical psychology at the time was reviewed although having said that another has now been added. Books reviewed covered topics including the effects of exercise on the brain and the relationship between therapy and culture. There was also commentary on the use of twitter in association with the blog. Two big studies published in Nature Genetics were reported in the news, both of which looked at genes strongly associated with Alzheimer’s Disease. There was also a look at a study using a new side-effects checklist for antidepressants. There were also interesting findings on the benefits of reminiscence therapy for memory and on communication of information on medications.
Psychology/Psychotherapy Articles Reviewed
Biological Psychiatry Articles Reviewed
Social Psychiatry Article Reviews
News from September 2009
Research in Dementia
Three genes associated with Alzheimer’s Disease were identified in 2 studies published in Nature Genetics. Amouyel and colleagues conducted a two-part study (Amouyel et al, 2009). In the first part of the study they undertook a Genome-Wide Association Study involving 537,029 single nucleotide polymorphism’s (SNP’s) in a French sample of 2032 people with Alzheimer’s Disease and 5328 controls.As there were multiple comparisons, they needed to control for this (with a Bonferroni correction) and a marker in the CLU gene on chromosome 8 (8p21-p12) showed a statistically significant correlation just above the threshold.
They then attempted a replication in the second stage which involved 3978 probable cases of Alzheimer’s Disease and 3297 controls. This second stage involved subjects from Spain, Belgium and France. They confirmed a statistically significant association of CLU with the probable Alzheimer’s Disease subjects and additionally found a significant correlation with CR1 on chromosome 1 (1q32). The researchers then estimated the contribution of each gene to the risk of Alzheimer’s Disease and estimated that the attributable risk for APOE (a well established risk factor for Alzheimer’s Disease) was 25.5%, for CLU it was 8.9% and for CR1 it was 3.8%. Nevertheless the CR1 did not show up in the first stage of the study.
In the second study, Professor Julie Williams and colleagues (including Professor Michael Owen) undertook another two part study. This involved ‘up to 19,000 subjects’ in the initial stages of the study, these subjects being recruited from Europe and the United States. Again, this was a Genome Wide Association Study. After quality control measures, they looked at 529,205 autosomal single nucleotide polymorphisms in 3,941 people with Alzheimer’s Disease and 7,848 controls. They identified one marker in CLU (the same gene identified in the study above) and a second in the PICALM gene on chromosome 11. Importantly both of these findings were replicated in the second stage of the study which involved 2,023 people with Alzheimer’s Disease and 2,340 age-matched controls.They then looked further to see if they could identify which areas within the gene were significantly correlated and produces some candidate regions. The team point out that there are other significant genes which wouldn’t have been identified in this analysis.
Thus the three identified genes were CLU, PICALM and CR1.
The CLU gene (Clusterin) which was identified in both studies encodes an apolipoprotein which together with APOE is found in the central nervous system as well as other tissues. There are many suggested pathways for the involvement of CLU in the pathology of Alzheimer’s Disease. Thus CLU is found in the amyloid plaques found in Alzheimer’s Disease and there is evidence also suggesting that it may be involved in the removal of Beta Amyloid from the brain (by forming soluble complexes which can cross the blood brain barrier) and may play a role in inflammation in the brain.
The PICALM gene which was significantly associated with Alzheimer’s Disease in the second study encodes a protein that is involved in endocytosis. Mutations in PICALM (phosphatidylinositol-binding clathrin assembly protein) may therefore interfere with the transport of materials into the neurons and the team suggest that synaptic vesicle cycling may affected (for another study looking at vesicle cycling see the study below which involved a newly discovered protein – the Flower protein which may be involved in Calcium regulation within the neuron emphasising the importance of endocytosis in neuronal functioning).
The CR1 gene which was significantly associated with Alzheimer’s Disease in the second stage of the first study, encodes a receptor for C3b protein. The C3b protein forms part of the complement cascade and again there is some evidence suggesting that it may be involved in the removal of Beta Amyloid. The CR1 receptor may be involved in the process of phagocytosis – when material is ingested by the immune cells.
Now that these gene associations have been identified it will be interesting to see further replication studies as well as studies examining the possible roles of these genes in further detail.
The N60 region of the RanBP9 protein has been associated with an increased production of Beta-Amyloid production using post-mortem and cell culture data and these findings may lead to the development of novel therapeutic interventions for Alzheimer’s Disease. This protein binds to another protein which is involved in the movement of RNA through the pores in the nuclear membrane. RanBP9 interacts with several other proteins also.
Financial Skills and Risk of Dementia
Predicting which people with Mild Cognitive Impairment go on to develop dementia is an area of current research interest. There are many studies using different methodologies looking into this question. One predictor is that the size of the Hippocampus (size is inversely correlated with dementia risk) which has a robust evidence base. However, a recent study provides evidence that financial skills may be another marker of risk and this has been widely reported in the media (e.g. here, here and here). A research team, just published in ‘Neurology’ found that people with Amnestic Mild Cognitive Impairment who scored poorly on the Financial Capacity Instrument were more likely to develop dementia. The sample group were people with Amnestic MCI and are therefore already a select group who have been assessed as having formal difficulties with memory. They were being scored on a tool which measures financial skills. The size of the study is relatively small (n=163) and of these, 25 people with Amnestic MCI went on to develop dementia.
There was found to be a significant association between a variant in the gene LINGO1 and Parkinson’s Disease and Benign Essential Tremor suggesting that this gene may be involved in both conditions. The gene variant is identified with approximately 5% of people with either condition. A gene sequencing process mrFAST (micro-read Fast Alignment Search Tool) has demonstrated utility in detecting duplicated genome sequences and the researchers have noted an increased number of copy number variants in genes which are located in a segment of the genome which underwent significant duplication in the ape/human ancestor. The process has implications for detection of diseases in which copy number variants need to be estimated and has also been used in the 1000 Genome Project.
Research on Antidepressants
The British Journal of Psychiatry featured two interesting studies on antidepressants. The first featured a patient rating scale for antidepressant side-effects – the Antidepressant Side-Effect Checklist (AEC) which is included in the Appendix for the paper (Uher et al, 2009). The researchers compared this patient rating scale with a clinician rating-scale, the UKU in 811 subjects with depression who were participating in an open-label trial comparing Nortriptylline with Escitalopram. The Nortriptylline was included because of a strong affinity for noradrenergic receptors (it would have been interesting to see whether similar findings would have occurred with Reboxetine). They found that after correcting for the severity of depression, the AEC scores predicted discontinuation of escitalopram (although curiously not the Nortriptylline) and validated the use of the instrument for the purposes of establishing side-effects in antidepressants. In another study, this time qualitative, the researchers explored the emotional side-effects of the SSRI’s. The responses from the participants were grouped into 7 categories and there were many interesting comments from the participants (Price et al, 2009). Both a reduction in ‘positive’ and ‘negative’ emotions were reported and there was some supporting evidence from an analysis of comments on several depression related online forums. The authors suggest further quantitative studies to investigate the findings from this study.
A new finding reported in the journal Cell is that cells are able to move using a newly identified mechanism which involves a folding of the membranes to form filopidia and this involves the use of a protein sRGAP2 which is associated with neurodevelopmental disorders. This may have important implications for the understanding of neurodevelopment.
News In Brief
In analysis of data from the Maastricht Aging Study, 35 healthy older adults without cognitive decline were compared with 30 older adults who displayed cognitive decline (using thresholds on several outcome measures) and in the latter group there was found to be a significant reduction in grey matter volume in the hippocampus, hippocampal gyrus, frontal and cingulate cortices. Some evidence that reminiscence therapy can improve memory in the elderly is provided from a review of reminiscence therapy studies that was published in Scientific American Mind which also looks at other outcome measures. It will be interesting to see the results of a meta-analysis once further studies are available.
A meta-analysis of prospective studies of people with cancer and comorbid depression found that depression was associated with a significant increase in mortality and the paper is freely available here at the time of writing as well as being reported on here. A PET study of 53 people with ADHD compared to 44 healthy controls provided evidence for reduced dopamine receptors in the Nucleus Accumbens.
Two large studies ( n=2978 and n=1760) published at PLOS Medicine, looked at how patients make choices regarding medications and amongst the findings, people were best able to understand medication outcome information if this was presented in simple frequencies (e.g. per 100 of the population). Further information on the trials can be found here and here together with a discussion of shared decision making here. An emergency mobile text message system for people unable to use their voices in calls is being trialled by a number of UK telecommunication companies.
There is evidence from a small Japanese study (n=48) that male teenage young offenders are more likely to misinterpret disgust as anger than male teenage non-offenders. An interesting study provided evidence that early stages of the visual perception process were influenced by cue associated emotions and memories. Subjects were presented with faces showing different expressions and the subject’s rating of the emotions in the expressions was correlated with the activation of their own facial muscles when the same faces were re-presented after having been modified to exhibit a neutral expression.
A comparison of longitudinal and retrospective studies provides evidence that people underestimate their experience of mental illnesss retrospectively. An American study of physician-patient interactions in primary care practices in Baltimore found a significant difference in communication-related outcome measures between white and black patients in areas including psychosocial interactions in consultations relating to blood pressure control. The researchers suggest that interventions focusing on doctor-patient communication may influence ‘racial disparities in the care of patients with high blood pressure’ although such research may have benefits in other areas of health care. The BMA has released a new document on ‘the effect of alcohol marketing on young people‘ and there has been wide reporting on this in the media.
A new gene association with deafness has been identified. Loxhd1 mutations impair functioning of hair cells and subsequently with hearing. Mutations of this gene were found in some families with deafness (in a genetic database with genetic samples from hundreds of families with deafness). A protein – called the Flower protein – has been recently identified and found to play a role in the processes of endo and exocytosis whereby neurotransmitters are packaged into vesicles, released from the neuron and the membrane resorbed. Aggregates of the protein form channels which allow the entry of calcium into the cell and the research team suggest that this protein could be responsible for the close and necessary coupling of endocytosis and exocytosis.
Evidence has been found that a species of New World Monkey – the Cotton Topped Tamarin are able to distinguish between ‘affiliate’ and ‘fear’ music produced by other monkeys. Such studies are useful for debates in Evolutionary Psychology. In a fascinating anthropological study of the fairy tales Little Red Riding Hood shows that this fairy tale probably has a very ancient origin. There were subtle differences across the world – for instance in China the wolf is replaced with a tiger. The most closely related versions to the modern European were those from Nigeria and Iran. There are many forms of analysis of fairy tales including psychoanalysis (see here, here and here for instance. A study published in Science (n-192) and using a public goods game paradigm (used in the study of group behaviour) provided evidence that using a reward strategy for ‘good behaviour’ produced better outcome (e.g. contributions to the group) than with the use of punishment for ‘bad behaviour’. A team looking into the extinction of Neanderthals have found the remains of late ice age animals in a cave in Torquay and the remains include what could be a 25,000 year old Hyena.
An application – healthii – has been developed with the intention of improving the well-being of people engaged in social networking online. A recent trial on Twitter at the end of August and the findings should be reported in the near future. A Twestival Local (a local festival on twitter) is taking place (see the site here) to raise money for charity. There are two types of festival – one is global and the other involves individual cities which are identified on the map here. This shows one of the many extraordinairy ways in which Twitter is impacting on society globally. A study looking at twitter provided evidence that 20% of twitters involve exchanging information about ‘products’. Epi Collect Software on mobile devices has been piloted which enables ‘citizen scientists’ to gather data for science projects incorporating their location within the data.
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