The paper reviewed here is  ’A Comparison of Psychiatric Consultation-Liaison Services Between Hospitals in the United States and Japan’ by Kishi and colleagues and freely available here. As the title suggest, the researchers make a comparison of consultation-liaison services in Japan and the Unites States and in the abstract there are a number of conclusions drawn. They begin with an introduction to their study. The researchers briefly describe some of their expectations of a comparison between the services in the two countries in this section.

The researchers describe their method in the next section. The researchers selected hospitals in Minnesota, USA and Kanagawa, Japan for the study. They write that cultural differences between the two countries might be reflected by the patterns of referrals to liaison services. They also state that the period of study was related to a change in the reimbursement fees for consultations although I wasn’t sure of the temporal relationship between the study period and this change. The catchment area of the Minnesota hospital was 3 million and in the Kanagawa hospital was 1 million. The researchers describe the data that was recorded during the study period. The researchers justify their use of an adjusted Length of Stay (LOS) figure which incorporates the timing of the consultation.

In the results section, there was significantly more men in the Minnesota sample (p=0.040), significantly more of the subjects were married in the Kanagawa sample – indeed almost twice as many proportionally (p<0.001) and significantly more employed in the latter sample (p=0.001). Surgical referrals seemed to be proportionally much higher in the Kanagawa sample than the Minnesota sample while the reverse was true for intensive care referrals although chi-squared and p-values weren’t displayed in the table for these figures. Interestingly almost twice as many referrals (proportionally) in the Minnesota sample had a past psychiatric history and this was highly significant (p<0.001). ‘Chemical dependency’ was the most common cause of referral in the Minnesota sample and ‘evaluation’ in the Kanagawa sample and both were significantly different from their counterpart values (i.e. in the other cities). Delirium was the most common diagnosis in the Kanagawa sample and depression in the Minnesota sample and again both proportions were significantly higher than those in the counterpart populations.

In the discussion, the authors suggest that cultural factors might not play a role in the differences in prevalence of depression between East Asian countries and western countries (however an interesting study is reviewed here). They then suggest that in Japanese culture there is a focus on the collective rather than the individual and that this may influence interactions with mental health services. They also comment on referrals from physicians to psychiatrists for ‘psychosocial issues’ which was a frequent finding in referrals. In their discussion the authors note a number of limitations to the study including the lack of controls which would be helpful in better understanding the cultural differences. Additionally they note that the selected hospitals may not be representative of other teaching hospitals in the respective countries.

As this was a comparison of retrospective data and they were interested in characteristics, the absence of primary outcome measures meant that in effect this was an exploratory analysis and adjustments may help to clarify which are the most interesting findings. The findings with regards to referrers and diagnoses would be areas that would be interesting to follow-up using a different paradigm e.g. case-controlled registry-based studies.

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The paper reviewed here is ‘Somatic Awareness in the Clinical Care of Patients with Body Distress Symptoms’ by Bakal and colleagues and freely available here. The authors describe Body Distress Symptoms thus

‘Symptoms of somatic or body distress (BD), more widely known as medically unexplained symptoms (MUS) or functional somatic syndromes, are characteri(s)ed by patterns of persistent physical complaints for which adequate examination does not reveal specific pathology’

Thus the authors equate Medically Unexplained Symptoms, functional somatic syndromes and symptoms of body distress in their definition. The authors go on to justify their favouring of the term BD and cite evidence suggesting that reattribution therapy which attempts to move the explanation for functional bodily symptoms to a psychological cause does not lead to an improvement in outcome measures. However the article is concerned with BD rather than RT meaning that the efficacy of RT would be explored in more detail in a systematic review which may result in more complex conclusions. The authors then go on to discuss the origins of Bodily Distress Disorder (BDD), discussing the three factor model and then focusing on how core symptoms might relate to the regulation of breathing.

I disagreed with the section on ‘depression and sadness in context’. While it is important to distinguish between ‘normal’ sadness and depression (for which there are many diagnostic criteria) the authors also make some suggestions about prolonged antidepressant use and then finish the section by stating that they do not think that antidepressant treatment is the answer. I would argue on the other hand that appropriate treatments are made only after a carefully considered assessment and that recommendations regarding the optimal treatment strategies should be guided by this individual assessment, the evidence base and the local treatment protocols.

The authors answer some of these points in their section on tacit knowing and somatic awareness. Even here I would argue that they are discussing an area which includes the clinician’s intuition and that where this is carefully honed it should be consistent with related areas such as the clinical evidence base. I would argue that the clinical evidence base is not an area distinct from clinical accumen but is an investigation of clinical data and an attempt to draw meaningful knowledge from this area. The definition of ‘tacit knowledge’ adds an air of mystery by referring to knowledge at the periphery of attention. Within this section, the authors refer to non-verbal material which the physician may use during the clinical process. Such ‘tacit knowledge’ can be systematically converted into explicit knowledge by a close study of such phenomenon and indeed various methods for measuring such factors have long since been developed and employed both in clinical practice and research.

I found the discussion of somatic awareness to be a more interesting contribution if we consider the mind to be both a function of brain as well as being better described by a symbolic system that differs from that used in discussion of the ‘brain paradigm’ (e.g. see here). I was interested however to find out a little more about how the authors intended to align ‘neurobiology’ and ‘consciousness’ as according to the paradigm discussed in the previous sentence this might not be a suitable starting or indeed end point. The authors invoke some of Damasio’s thoughts on the mind-body relationship. My interpretation of what the authors were trying to say was that there is mind-brain-body relationship and that as the body is involved in this relationship it can serve as the focal point for discussions and that this is just as valid as making the mind or the brain the focal points. The justification for this would be that any ‘focal’ point is in itself a simplification of the more complex relationship that occurs between the three and so it doesn’t matter which of the triad serves as this focal point it will still be a simplification and explanations will always return to the complex interactions between mind, body and brain. However by using the body as a focal point for this discussion, the model is apparently made more accessible.

In the final section the authors consider how ’somatic awareness’ might be incorporated into medical practice. Again I disagreed with many of the points in this section. For instance, the withdrawal of medication was difficult to justify as patients may be on a number of medications for different conditions. Although some may not be prescribed as psychotropics they may in some cases have such side-effects and it would be useful to see the management suggestions in such cases where withdrawal is not possible. As above, a blanket statement about medications does not address the complexities of individual needs and even on a theoretical basis there are many counters to this suggestion. Encouraging a focus on introspection and monitoring both symptoms and bodily sensations seems to be a useful approach that could be developed further in a subsequent article again with reference to the evidence base.

In summary, the authors broach psychosomatic issues by consideration of ‘body distress’ although I found a few statements that seemed axiomatic and could be argued to be too simple to address the complexities of individual needs without careful consideration of process, the evidence base and consequences. It is useful however to have discussions in this area.

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The reviewed article is ‘Depression: An important comorbidity with metabolic syndrome in a general population’ by Dunbar and colleagues from 2008 and freely available here. In the abstract the authors conclude that

‘Metabolic syndrome was associated with depression but not psychological distress or anxiety‘

So is it possible on the basis of this study to draw the above conclusions. The researchers completed three cross-sectional studies in rural Australia. The first thing to say is that as the study was conducted in rural Australia the findings might be specific for this population. It seems more likely that this should be generalisable. However if we consider urban versus rural settings for instance a number of other factors come into play ranging from the structure of health service provision through to social networks and lifestyle which might influence either metabolic syndrome or depression or both. Men and women ‘aged 25 to 84 years were selected from the electoral roll’ by a random sampling method. I couldn’t find a reference to the type of random sampling method that was used but it is reasonable to suppose that there was no obvious selection bias as a result other than the self-selection that results from participation. The authors do note however that the study did not include those that had left the region and this is relevant in the context of the above point about urban versus rural settings. The researchers identify a number of outcome measures including psychosocial factors and factors relevant to the diagnosis of metabolic syndrome such as fasting glucose and waist and hip circumference. The criteria for metabolic syndrome were clearly identified. The researchers also used the Hospital Anxiety and Depression Scale, a commonly used scale which aids the assessment of depression in the hospital population. However the authors also used the ‘Kessler 10 measure’ which I wasn’t familiar with and describe it as a five-point likert scale where cumulative scores result in categorisation into low and moderate-high levels of ‘psychological distress’ in the last 4-weeks. The internal consistency values for K10 and the HADS subcomponents were provided ranging from 0.79 to 0.87. The primary outcome measures (or at least I presume they were the primary outcome measures) were clearly stated and the author examined the relationship between anxiety, depression and the metabolic syndrome. The statistical analysis of other relationships between the many variables that were used in the study was also clearly stated. 409 subjects met the criteria for the metabolic syndrome and a comparison was then made between those with and without the metabolic syndrome. I didn’t particularly understand the following within the results section

‘Participants with the metabolic syndrome were more likely to have moderate to severe depression (10 vs 6.9%, p = 0.069)‘

In the remainder of the sentence the authors write that with regards to another measure there was no statistical significance. However the p value above would not be significant either (at the 5% level). However the researchers did find a significant difference between metabolic syndrome and the diagnosis of depression (i.e. without reference to specific subtypes such as moderate or severe) and this time the difference reached a significance of 0.013 and depression scores were 3.41 versus 2.95. Thus there is a mean difference of roughly 1.5 points on the HADS depression subscale (I presume that it was this subscale although not stated explicitly in the sentence) at the group level.

So the relationship appears significant but the direction of this relationship is unclear as it was a cross-sectional study. A longitudinal study might be able to shed light on the directionality of the relationship. The authors speculate that an inflammatory pathway might mediate the link between depression and the metabolic syndrome.

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News in Brief

The National Institute of Clinical Excellence has released guidance on mental wellbeing at work. The document has a wide audience including members of the public (where applicable in the UK) and complements previous NICE guidance in the workplace. The quick reference guide contains 5 recommendations relating to strategic/coordinated approaches to mental wellbeing, assessment of opportunities for wellbeing of employees, flexible working, the role of line managers and supporting micro, small and medium-sized businesses. This has been widely reported with a number of articles looking at how these recommendations might impact on health services themselves (see here, here and here). This comes at the same time as a report by the Chartered Institute of Personnel and Development (CIPD) which produced findings from a survey of 2000 employees which included results relating to mental health (covered here). The researchers in an american study covered here found that of 472 million prescriptions for psychotropic medications prescribed between August 2006 and July 2007, only 1/4 were prescribed by psychiatrists. Virtualised desktops save time in booting up the computer and in this article a proprietary system using virtualised desktops was suggested to save clinicians 30 minutes on average each day

Research in Dementia

There is coverage here of a 20-year longitudinal study published in Neurology which identified associations with the development of mild cognitive impairment and it will be interesting to see how these findings inform further research in this area. This article looks at another study published in Neurology this time on Frontotemporal Dementia (FTD) and finding that 42% of subjects had a family history on the basis of a related outcome measure  (see here for further information). There is coverage of the recent Society of Neuroscience conference in Chicago over at the Alzforum and this featured a number of presentations on Alzheimer’s Disease.

Research in Pervasive Development Disorders

A neuroimaging  study (n=88) compared people with Asperger Syndrome and Autism with controls and found a significant difference between the Asperger and Autism groups in terms of structural MRI findings with the latter group having increased grey matter volume in the frontal and temporal lobes (Toal et al, 2009). However it will be interesting to see this data be included in a meta-analysis with other similar studies as well as to see the findings of larger replication studies. This study is timely given the recent discussion about dropping the diagnosis of Asperger Syndrome (see below).

Research in Psychosis

There is a discussion here of some of the recent genetic evidence of similarities between Schizophrenia and Autism in terms of analysis of copy number variants. The possible role of a form of interneuron known as the gliaform cell in psychosis is discussed in this article.

Publications on Affective Disorders

The National Institute of Clinical Excellence has released guidance on the treatment of depression in people with chronic health problems – the quick reference guide is here. A small case series which looked at deep brain stimulation for severe depression provided some evidence of efficacy although given the sample size, it will be interesting to see the outcome of a relevant systematic review or meta-analysis which incorporates this data.

DSM-V

There was discussion recently of the diagnosis of Asperger syndrome being dropped from the next edition of the DSM and this will mean an expansion of the autism diagnostic category. This was originally discussed in a New York Times article (which requires (free) registration). The article features an interview with Dr Catherine Lord, who is one of 13 members of the working group on autism and neurodevelopmental disorders. The group are considering a number of amendments to the autism diagnosis including the addition of comorbidity that have been associated with the condition including disorders of attention and anxiety. However the suggestion regarding Asperger syndrome has not yet been ratified by the group. There have been a number of responses in the media. This article contains interviews with a doctor who runs a clinic, a parent of a child with Asperger’s syndrome and the president of a non-profit organisation for raising awareness of the condition. There is some information on the DSM-V process here.

Psychiatry 2.0

There is further discussion of the DSM-V Asperger syndrome diagnosis on the left-brain, right-brain blog and at the time of writing there are 87 comments, testimony to the interest this discussion is creating. Dr Grohol also covers this over at Psychcentral. At the ISCI healthcare blog there is an article looking at some of the ways in which twitter is being used in healthcare. MindHacks has another news roundup in ‘Spike Activity‘ and included is a link to an interview with Terry Pratchett about Alzheimer’s Disease. The ‘Heal My PTSD‘ blog contains a round-up of Post-Traumatic Stress Disorder (PTSD) news including the use of a virtual reality environment for re-experiencing trauma as part of a therapeutic intervention. This BBC article looks at some of the ways web 2.0 technology is being used by the research community. Patients in the USA are beginning to carry their healthcare information around with them in iPhone apps as reported in this article. The Science in the Open blog has an article looking at how an open collobarative framework might change science (Science 2.0) with the possibility of the science being separated into data acquisition, data analysis and dissemination of results. An article here looks at recent research which counters the argument that use of the internet has casued people to become more isolated. They cite research which suggests that people are not more isolated than in 1985 and elsewhere that people who use the web regularly are more likely to participate in social activities such as meeting up with friends . See here for more information.

Miscellaneous Research

A study of babbling in babies (covered here) found evidence that after only an hour’s exposure to a new language, the baby’s babbling with the speaker of that new language differed from that with speakers of the native language.

References

Toal F, Daly EM, Page L, Deeley Q, Hallahan B, Bloemen O, Cutter WJ, Brammer MJ, Curran S, Robertson D, Murphy C, Murphy KC, Murphy DG.Psychol Med. 2009 Nov 6:1-11. [Epub ahead of print]. Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study.

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The podcast reviewed here is another in the University of California in Los Angelos grandround podcasts. This could more properly be called a videocast. This episode focuses on the genetics of late life depression and is presented by Associate Professor Warren Taylor. The audio and video quality are both of a high standard and I found it easy to focus on the content of the presentation. Taylor looks at a number of the risk factors for and associations with late life depression. He then focuses in particular on the genetic associations suggesting along the way that these might be indirect, mediated through vascular pathways for example. Taylor then discusses some of his own unpublished research going through some of the primary outcome data as well as the exploratory analysis. I thought this was a useful overview of an expanding area of research. I’ve been impressed by the UCLA grandround podcasts and like the Maudsley debates which are also available in podcast format this seems to offer a very useful model for psychiatry departments to communicate information about some of their activities. This opens up a number of other possibilities that range from seeing what people in the field are doing through to gaining overviews of a more specialised area of interest. It will be interesting to see if this podcasting approach expands into other departments. This episode is another interesting addition to the series.

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The blog reviewed here is ‘FABLE‘ an acronym for ‘Fictional Autobiography of Life Experience’. I first came across the blog via the author Cole Bitting’s Twitter profile after exchanging a few messages with him on Twitter. So here are the results of my look at the blog….

Appearance and Design

The title pane consists of the blog title with an effective shadow effect on a woody background. The main background is a slightly off-black colour (i’m not particularly good at naming some of these subtle shades of colouring!) with white text. Individual articles are demarcated by a white dotted line at the end of each post. The reader can navigate by selecting the page numbers at the very bottom of the page. On the left hand side there is a link to a descriptions of songs that Bitting refers to in the text. There is an About section in the title pane and on the left hand pane there are links to an RSS feed as well as links to Web 2.0 resources such as Twitter. There are also occasional images that complement the text.

Articles

The first article is dated 28th September 2009. In this first article, Bitting tells us about fables and our relationship with them. Within this first article Bitting also tells us of the high regard in which he holds Damasio’s work ‘The feeling of what happens. Body, emotion and the making of consciousness’. I, like many people have found Damasio’s writing accessible and extremely interesting and used this in the foundations for the building of a model of the role of the Insular Cortex in emotional regulation as Damasio’s work has influenced people such as Craig in his development of a model of the Insular cortex (see here). In the second article, which is philosophical in nature, Bitting produces one of the statements which will feature again in the blog – the distinction between what is useful and what is truthful. As I understand it, Bitting is arguing that when a narrative is formed does not necessarily represent an underlying truth but instead relates to utility. In this ‘Perspective: Objectify Yourself, Witness Life’ article, Bitting discusses some foundations for the neurobiology of first person perspective and what I found really interesting here was his use of triangle and inverted triangle symbols for concepts creating an effective symbolic shorthand. In ‘Open Up, Confront the Fury’, parts 1 and 2 (of a 3-part essay – with the final part not published at the time of writing) Bitting looks at how writing can be an effective means for confronting and managing disturbing emotions (in psychodynamic terms this is equivalent to sublimation). However this is quite thematic in Bitting’s writing.

Summary

If I were to summarise Bitting’s writing, I would characterise an underlying theme of exploring the neurobiology of narrative therapy using Damasio’s works as a foundation for this process. However, Bitting himself has an elegant style of writing with emotional depth and so the reader is able to enjoy his writing on another level while exploring what is a fascinating area of inquiry.

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The audiobook reviewed here is ‘The Beginner’s Guide to Dream Interpretation’ by Clarissa Pinkola Estes who also narrates the audiob0ok. Firstly turning to the narration, I thought this was exceptionally good. Compared to the narration in the previous audiobooks I have reviewed here, which have also been of an exceptional quality, Estes brings a unique approach.  She uses a style which gave the impression of listening in to her having an informal conversation interspersed with relevant anecdotes and always in a very light-hearted manner. She is able to do this while covering the introductory material to dream interpretation. There was some overlap with material covered by John Betts in his excellent podcast series on Jungian Analytic Psychology (e.g. see reviews here, here, here and here which link to relevant episodes). Thus we see familiar themes such as the benefits of keeping a sleep diary and Estes refers in the work to Jung’s approach to dream analysis. As this is a relatively short introductory guide to dream interpretation it serves the purpose of informing those new to the field as the title suggests and Estes attains this goal succinctly by explaining the central concepts while holding the listener’s attention. What I found particularly interesting in this book was the description of the common types of dreams that occur across many cultures including falling, flying and animals amongst others. Indeed listening to this list triggered one of my recent ‘forgotten’ dreams and perhaps reinforced that many of my dreams would fit into these common themes (although it could of course be coincidence!). However another fascinating resource reviewed earlier on the blog – the Dream Journal (see review here and site here) consists of dream narratives entered by members of the forum. A look at this at the time of writing revealed common themes or content in dreams including friends, relatives, searching, ‘peaceful’, fear, water and driving! While this is not a formal research area and members are self-selected (meaning it might not be representative of the general population) there are sufficiently large numbers of dreams to be able to ask some interesting questions. This site also shows that inquiry into the subject of dreams can follow both a qualitative and quantitative approach and while it is inherently difficult due to the nature of dreams it is not unreasonable to expect that such study will (and has) produced useful results. It is interesting to note that dream analysis has preceded the psychoanalytic movement and indeed the more formal analysis dates back many centuries. Nevertheless the Swiss psychiatrist Carl Jung contributed many valuable insights into this field and as Estes is a Jungian analyst she is able to communicate many of these insights to the reader. I found this to be a very useful resource for those new to the field of dream analysis.

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The article reviewed here is ‘The Alignment of Information Systems with Organisational Objectives and Strategies in Health Care’ by Bush and colleagues. In the conclusion in the abstract the researchers ‘confirm’ that alignment of IT is an important area in healthcare organisations and that

‘Finally, it contributes by suggesting future study of alignment’s predictors and effects in health care organi(s)ations‘

In the introduction, the researchers distinguish between strategic alignment of information systems and short term developments which are responses to new technology and use in other services amongst other reasons. They identify clear research questions such as the process by which healthcare services choose their information systems as well as barriers and incentives for managerial uptake of IT. They then cite evidence which supports their central argument for the importance of alignment of strategy and IT and examples of failure of IT systems when there is no clear alignment.

The researchers then describe the methodology for their study. They have identified ‘20 healthcare organi(s)ations in a mid-western US city’. There weren’t explicitly stated inclusion criteria for the selected organisations and the researchers note that they chose a heterogenous group of organisations to represent variation in healthcare services. A structured interview was used but I thought the methodology for analysis of subject’s responses was not clear. The researchers identified people within the services who procured the IT systems and approached them to participate in the study.

The organisations chosen included a mental health service, acute and chronic care (presumably general medical) settings and outpatient clinics. The data on employee numbers and information system details are included also. There are a large number of sections in the results section corresponding to the components of the interview. They identified a number of strategies within the organisations that were objectives for alignment with IT systems and these included patient safety, growth, technology focus and staff development. They then describe the results for methods that managers used to choose IT systems. These methods included formal evaluation, return on investment analysis and ‘board of directors approval’. They then described the interview results relating to factors which supported uptake of IT systems. The key actions for managers which contributed to uptake seemed to be site visits. With regards to organisational characteristics facilitating uptake subjects most commonly thought this to be the involvement of senior management. Managerial actions which perceived to hinder uptake included involving ’stakeholders too little’, ineffective communication and the decision making process itself. The hindering characteristics of the organisation included a ‘lack of management support’, ‘lack of resources’ and ‘resistance to change’ amongst others. The researchers then propose a system for alignment which involves identifying the organisational strategy, envisioning the information system through to implementation.

The study produced some interesting results although I would have been interested to learn more about the methodology for the analysis of results. The results here are higher level and subsequent research can move in various directions from the use of a different sample set with other specificied qualitative methodologies through to the use of quantitative methodologies including large surveys and cost-benefit analyses of information technology uptake when services have been stratified according to the results of the study.

References

Bush M, Lederer A L, Li X, Palmisano J and Rao S. The Alignment of information systems with organisational objectives and strategies in health care. International Journal of Medical Informatics. 78. 446-456. 2009.

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The paper reviewed here is ‘Follow-up psychotherapy outcome of patients with dependent, avoidant and obsessive-compulsive personality disorders: A meta-analytic review’ by Witold Simon. The title summarises the broad aim of the study and in the abstract, the authors conclude that

‘The study indicates that therapy gains are usually maintained at follow-up for Cluster C clients treated with cognitive-behavio(u)ral and psychodynamic approaches as well as social skills training‘

Just to recap, the DSM-IV cluster C personalities refer to the anxious avoidant personality disorder (AVPD), the dependent personality disorder (DPD) and the Obsessive-Compulsive Personality Disorder (OCPD).  In the objectives section, the authors clearly outline the questions they aim to answer including the efficacy of therapy on specific and general outcome measures, efficacy of follow-up, relative therapy responsiveness of individual personality disorder subtypes and relative efficacy of therapy types. The methodology is clearly outlined incuding databases used, search terms within the databases and inclusion criteria for papers. The researchers have used detailed criteria for describing the papers and students were trained to use these criteria with the papers. The criteria scored highly on inter-rater reliability. The authors identified 15 studies between 1982 and 2006. The authors commented on the heterogeneity of treatment approaches as well as in a number of other variables. For each of the four questions they posed, the authors described the number of randomised controlled trials and non-randomised studies. In the results section they state that all of the treatments except brief dynamic therapy were effective in showing ‘improvements’ by the end of therapy compared to controls and referred to Table IV. However on inspection of Table IV, I noted that effect sizes were given but I wasn’t clear about which outcome measures the effect sizes related to. In the section on follow-up therapy the results are discussed for 3 and 6-month follow-ups and given the range of therapies examined the significant findings cover many therapies in individual trials. I couldn’t identify a statistical pooling of study results in the table or the section on follow-up studies. Indeed on closer examination, I could find no reference to effect sizes in the tables or to outcome measures nor any other indication of the effects of treatment. In the text, again I could find no reference to these measures and instead there are general remarks about individual studies or small groups of studies. In the section on differential effects according to diagnosis, the authors report that these results are ‘inconsistent’ and describe these qualitatively without any obvious reference to a pooled-analysis which might at least offer a statistical answer. A little later in the conclusions, the authors refer again to the effect sizes and here they pool the data for effect sizes using Cohen’s Classification. The effect size they explain refers to the percentage of people getting better with therapy. However it is not clear what ‘getting better’ means as improvement might be considered differently in each study and would make comparisons difficult. I didn’t see any other quantitative results given in the discussion.

In summary, perhaps the most convincing evidence was provided for the follow-up data, and here the authors have included the pooled effect sizes although there still remains the question of what exactly is meant here by ‘an improvement’. There is also the question of how diagnoses have been established in each study. For instance there has been a suggestion that anxious avoidant personality disorder has an overlap with social phobia e.g.  (Tillfors and Ekselius, 2009). If this is the case it would be interesting to see how social phobia has been excluded in these studies although the authors have referred to the heterogeneity of methodologies in the studies. The lacks of explicitly stated pooled effect-sizes in other sections of the paper make this difficult to interpret and one obvious comment is that a meta-analysis should be repeated as more study results become available although this can be said for all meta-analyses.

References

Tillfors M and Ekselius L. Social phobia and avoidant personality disorder: are they separate diagnostic entities or do they reflect a spectrum of social anxiety? Isr J Psychiatry Related Sci. 46(1). 25-33.

Witold Simon. Follow-up psychotherapy outcome of patients with dependent, avoidant and obsessive-compulsive personality disorders: A meta-analytic review. International Journal of Psychiatry in Clinical Practice. 2009. 13(2). 153-165.

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The article reviewed here is ‘Valproate and Neuroprotection Effects for Bipolar Disorder’ by Murad Atmaca. This is a brief review looking at the potential neuroprotective effects of Valproate in Bipolar Disorder (BPaD). There is no stated methodology for this review. The author considers the evidence for BPaD as a neurodegenerative process by focusing briefly on one study showing a reduction in glial cells in area 9. There is then a look at Proton Magnetic Resonance Spectroscopy imaging studies which allow visualisation of cell components (e.g. choline-containing compounds which are found in neurons and glial cells). Atmaca then focuses on one of these compounds – N-acetylsaspartate (which is found in neurons alone) and builds the argument for suggesting that this may not primarily be a proxy marker for neuronal structural integrity one of the assumptions made in the literature as there is a reversibility in lowered NAA levels. However in order to progress, a decision has to be made about what NAA does represent and Atmaca seems to settle on the conclusion that lowered levels of NAA are equivalent to a loss of neurons or related losses (e.g. loss of axonal function). Using this assumption, Atmaca then looks at some of the MRS research in BPaD and notes that in one study the ratio NAA/CHO was lower in controls compared to those on a combination of Quetiapine and Valproate. There is then further indirect evidence of a protective effect of valproate against excitoxicity. A number of cellular mechanisms are then considered – effectively Atmaca attempts to outline some possible pathways through which any such effects might occur before finishing with a look at some evidence of reduced brain volume reduction with Valproate. Although cellular mechanisms would be expected to form the basis for drug effects, the more convincing evidence for drug effects come from sufficiently powered longitudinal randomised-controlled trials preferably over a reasonably long time period. However, this paper is concise and Atmaca puts some pieces of the jigsaw puzzle together although time and further evidence will tell if these are the right pieces.

References

Atmaca M. Valproate and neuroprotective effects for bipolar disorder. International Review of Psychiatry. August 2009. 21(4). 410-413.

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News in Brief

There is preliminary evidence that inflammation in the hippocampus may be associated with schizophrenia although it will be useful to see the results of further studies in this area. In a study (n=109) of people with depression and controls there was found to be an association between depression and overestimated retrospective recall of somatic symptoms and this is just one of many ways in which depression and physical illness may have complex interactions. There was a recent study which used a large number of outcome measures which investigated collectivist versus individualistic cultures and the authors suggest that the former are associated with a lower genetic predisposition to depression. However it is important to note that there are cultural differences in the use of diagnostic classifications (e.g. see this review).

In the BJPsych there is an interesting article by Professor Michael First who writes about the potential for harmonisation of DSM-V and ICD-11 which is a widely discussed topic (First, 2009). There are a number of points of interest in the article and he notes that there are investigators involved with revisions of both systems which should help to contribute to attempts to harmonise both systems. The discussions around these systems will no doubt increase. There is also a supplemental issue to the BJPsych which focuses on long acting injectable antipsychotic medication with review articles and original research*. Articles included a systematic review of RCT’s and observational studies of oral versus long acting injectable (LAI) depots, a review of psychopharmacology and side-effects of LAI’s, a systematic review of second-generation LAI’s and a review of  UK prescribing practice amongst many other articles. There is a recent study which provides evidence of a relatively small difference in the rate of decline of memory in those with Alzheimer’s Disease with or without diabetes. Those with diabetes had a slower rate of decline (although the effect size was relatively small) and it will be interesting to see further replication studies in this area.

Technology review have a collection of images about representing 100 years of visualising the brain. A comedian has been invited to contribute a humorous perspective to a production on mental health by a primary care trust. There is a clip of the performance in the article and the argument is that the comedy can help to overcome stigma through education. You can see the responses of members of the audience in the clip. There is a recent statement from a geneticist Professor Paabo that Neanderthals and humans interbred according to analysis of the Neanderthal genome (see also here). The specific evidence base for this conclusion is not clear** and it will be useful to see further evidence when it is published. However the remaining question is whether or not the Neanderthals contributed to the modern human gene pool which is a separate although related question which may be answered with the completion of the sequencing of the Neanderthal genome. If this were so, it would have many implications. Another paper on genetic material – heterochromatin may in the future help to answer the question of whether the offspring would be sterile.

Psychiatry 2.0

Dr Shock links to an educational video about the redesign of the PubMed interface which is useful for those undertaking literature reviews, database searches and related activities. Sandy Gautam has started a new blog – My 2 Brains and in this post he reflects on twitter including a look at how it relates to the expression of self. MindHacks has his weekly round up here. There is an article here about web-based healthcare. The Journal Cell has an article on twitter and at least one of the scientists quoted in the article found that it was useful in keeping up to date with developments in their field.

** I couldn’t identify a relevant press release at the website

References

*November 2009, Vol 195, Supplement 52

Michael First. Harmonisation of ICD-11 and DSM-V: Opportunities and challenges. The British Journal of Psychiatry. 2009. 195. 382-390.

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Psychiatry 2.0 refers to the Web 2.0 applications which are relevant to psychiatry. Related areas include Health 2.0 and Medicine 2.0.

Last Updated 31st October 2009

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In the 28th October edition of the Nature Neuropod, Kerri Smith interviews researchers who have published recent interesting research in the field of neuroscience. In one of the interviews Smith talks with researcher Ted Abel who has identified a cyclic AMP signalling pathway that is modified in the hippocampus during sleep deprivation such that the levels of phosphdiesterase-4, which degrades cAMP are increased. Further when this pathway was blocked, sleep deprivation-related memory impairment was reversed. There may be therapeutic implications pending further research. There is also an interview with Professor Pasko Rakic who has been looking at the evolution of the central nervous system in mammals. There is  a fascinating interview with Eve Marder about individual differences in the central nervous systems of crabs, moving away from the paradigm of averaging group properties. This question of the difference between individual and group properties is an important one which is relevant to many different areas of research in the life sciences including clinical sciences (see for instance the paper reviewed in this article). There is also a look at research on place cells – which code for spatial locations. The slow pace and clearly enunciation work well for the complex material that is carefully explained for the listeners.

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The book reviewed here is ‘The Greatest Show on Earth’ by Richard Dawkins. Both Dawkins and his wife actress Lalla Ward narrate the book in an engaging style and in the process convey the awe of nature that permeates the book. Indeed for those unfamiliar with Dawkin’s works – he is a champion of communicating the beautiful and at the same time inexorable logic of evolution while at the same time answering the common criticisms that have been levelled against evolution. In my opinion, Dawkins writing represents the embodiment of rationalism in search of an ephemeral eternal truth about nature which because of the subject of its enquiry takes on a transcendent quality. Dawkin’s latest work references many of his earlier works, reiterating important nuances in evolutionary theory such that it parallels a collection of axiomatic proofs building to a final conclusion. The conclusion in this case is the essence of several billion years of evolution on Earth. Dawkins examines the possible origins of life with a fascinating reference to Darwin’s profound passage on the chemicals in a pond which might contribute to the beginnings of life. He covers artificial, natural and sexual selection and illustrates each of these with elegant examples that reaffirm the concepts. Indeed what it is striking is Dawkin’s ability to effortlessly take such examples which are selected from across vast expanses of time as well as geographically and phylogenetically disparate regions and which reveal a supreme familiarity with the natural world. Indeed it seems that any debate about the underlying principles of evolution should begin with a demonstration on both sides of such familiarity particularly as the significance of the natural world is rarely contested. Dawkins also discusses the gene pool and this part in particular I had found interesting. I had overlooked that the individual and successful genes are part of a gene pool within the organism and this relationship between an individual gene and the remainder of the genome (or genomes if the wider group is considered) adds a necessary layer of complexity. For instance, the small changes in genes which may initially cause problems can be compensated by the actions of other gene products. This is interesting in the light of recent evidence that in people, each generation results in an average of 100 mutations in the genome*. In this regards it was also interesting to note that different parts of the genome have staggeringly different rates of mutational change with such changes being particularly rare in histone-related genes. On further reflection about some of the underlying evolutionary principles, I thought that these might easily be abstracted in mathematical form and this became more evident when Dawkins describes one of the computer programs he had written to simulate evolutionary changes (indeed genetic algorithms have been particularly successful in real world applications). This again testifies to the skills and effectiveness of Dawkins in translating such refined arguments into a format that is easily accessible. He has in the process developed a language which combines the underlying logic of evolution with those additional components of knowledge which reach out to a wider audience**. This is another indispensable work for those with an interest in the wonders of the natural world.

* It is tempting to suppose that multi-gene mutations may produce significant changes in a network effect although such an effect is improbable if such mutations are independent (given the size of the genome)

** It would be interesting to see if such rules could form the basis for an open-source educational and research software paradigm

References

Richard Dawkins. The Greatest Show on Earth. Narrated by Richard Dawkins and Lalla Ward. Random House Audio Books. 2009.

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The blog reviewed here is ‘Doctor Dymphna’s Diliberations‘.

Appearance and Design

The blog has a black background and a slightly off-black background in the central pane on which the white text of the articles is overlaid. The title pane consists of the blog name together with a colourful photo-like design. At the time of writing on the right hand pane there is an ‘About’ section for the blog, links to the associated twitters, blogroll, category cloud, recent posts and links to other websites. The blog can be navigated via an archived index also on the right hand pane. The blog is hosted at WordPress.

Articles

In the first post, there is an explanation of why the blog was started as well. Although there is a suggestion of abandoning anonymity, I couldn’t find a reference to the author’s name although this is apparently identifiable from the related twitter. As I couldn’t find a reference to the same name in the blog, I have refrained from using it in case they’re not equivalent. What I found interesting was that the author uses a combination of mindfulness-based therapy, cognitive-based therapy and pharmacotherapy. Some of the posts broached broader issues which could be argued by some to cross over into other distinct and separate domains. There are also interesting articles such as this on lifestyle approaches based on the research literature. The author also writes about her son’s condition and how this affects her. This article looks at some of the authors reasons for tweeting and indeed it is through the twitter account that I first came across this blog. There are also a number of book and film reviews.

Conclusions

This is a relatively young blog which usually has a few posts every month. The articles are sufficiently long to explore the topic of interest and to present these from the author’s perspective. I found some of the psychotherapeutic posts to be particularly interesting.

Addendum (10.11.09)

The About section has subsequently been updated – the author of the blog is indeed Dr Elizabeth Cordes

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The article reviewed here is a short report in the Lancet Neurology by Adrian Burton on the applications of YouTube in neurology with a particular focus on neurodegenerative conditions (Burton, 2008). Burton looks at a few channels on YouTube and provides opinions on the likely success of such channgels with the helpf interviews with relevant figures in the field. Although a number of channels are discussed, two in particular are focused on – the UK Alzheimer’s Society channel and the UCSF Memory and Aging channel. There is a discussion of whether these channels will remain in the ‘background’ in terms of viewings given the competition they face from other videos on the site which include those from television companies as well as viral marketing videos from large companies trying to reach a global audience.

At the time of writing, the Alzheimer’s Society channel has 53 clips uploaded. In this clip for instance, Neil Hunt, Chief Executive of the Alzheimer’s Society talks about Alzheimer’s Disease. At the time of writing the channel also has videos in Urdu, Punjabi, Hindi and Bengali. There are also interviews with people with Alzheimer’s Disease who describe their experiences and discuss some of the stigma that has been associated with the condition as well as educating viewers about misconceptions which contribute to this stigma.

The University of California San Francisco channel contains a number of videos about dementia including one on cognition in dementia, moral reasoning in Frontotemporal Dementia (FTD), FTD and emotions, and in this video Dr Bruce Miller explains how useful YouTube can be in education about dementia.

I had looked at videos on vascular dementia on YouTube in this post and concluded at that point that it required a lot of searching to find a few videos that were useful (which of course depends on the purpose of the video and the needs of the audience). However it is only a matter of time before this becomes a very useful medium. There are a number of reasons why I would expect this to become a more important medium for education purposes. Firstly it is not unreasonable to assume that the number of videos on YouTube will continue to increase. If a static proportion of these videos comprises useful educational material then such an increase would be expected in such educational material also. Secondly indexing methods may be expected to improve, be this within the YouTube site itself or through external sites which index some of the useful material in YouTube. The assumption here is that the videos will remain on YouTube indefinitely. Thirdly the methods for video production within the general population may be expected to improve with time as more sophisticated technology becomes available to the general population thus facilitating communication. Fourthly the proportion of the population (globally) with internet access will be expected to increase with time and assuming that a certain proportion of this population contributes videos to YouTube this would again be expected to increase the amount of educational material available (which ties in with the first point) but may also improve the drive for video production as there should be a larger potential audience for this material.

The article is a useful starting point for discussion around this topic and it will be interesting to see developments even within the next year in this field.

References

Burton A. YouTub-ing Your Way to Neurological Knowledge. Lancet Neurology. Vol 7. December 2008. pp1086-1087.

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The article reviewed here is ‘Implicit and Explicit Aspects of Sequence Learning in Presymptomatic Huntington’s Disease’ by Ghilardi and colleagues and freely available here. In the abstract, the authors conclude

‘These results suggest that both explicit and implicit aspects of sequence learning may be impaired before the onset of motor symptoms. However, when attentional demands decrease, explicit, but not implicit, learning may improve‘

Thus the authors compare and contrast implict and explicit learning in Huntington’s Disease (HD) for a very specific task. The study revolves around a sequencing task and some assumptions. The assumptions are that in this case, implicit and explicit learning can be demarcated according to different elements of the response to the task. Thus for instance they argue that as learning proceeds, the movements become more efficient, saving energy and that this occurs implicitly. They also argue that the number of anticipatory movements in the task is a proxy for explicit learning. However it could be argued that there can be an overlap. Thus the subject could tire of the movements involved in the task and consciously seek to perform these actions more efficiently. Further these actions could be accompanied by an internal dialogue which could almost certainly be considered an explicit form of learning or it could occur non-verbally where the subject nevertheless attends to this goal. Similarly for the initial period of learning the task involves consideration of the sequence of events but here too it could be asked ‘does the learning take place consciously’ (the same could, I think, be asked of this example where the question could be asked  ‘is this chimp consciously or explicitly aware of what he is doing?’). In effect then, it might be reasonable to ask if implicit or explict learning are continuous rather than discrete functions or even if this characterisation is task specific such that it might not be possible to generalise from single tasks.

The researchers have considered a large number of variables which are given in tables 2 and 3. Interestingly they mention that there is a ‘post-hoc analysis’ and a null hypothesis is not clearly stated although the authors do discuss their interpretation of the different components of the task response. The researchers have corrected for the multiple comparisons by using Bonferrini corrections. On the tasks, the subjects with presymptomatic HD (the number of CAG repeats averaged 41. The greater the number the greater is the risk of conversion) performed significantly worse on the implicit and explicit learning components of the tasks as interpreted by the researchers. My initial impression was that the explicit task involved sequencing and might under Baddeley’s model of working memory be attributed to the central executive. There would be expected to be executive dysfunction if the frontal-subcortical loops are affected by the disease process which is seen in HD. The only question here is whether or not there is interruption of the frontal-subcortical loops as this is prefmanifest HD. The researchers also found that if they reduced the complexity of the task there was no significant difference between the premanifest HD subjects and the controls on the ‘explicit learning’ but there was a significant difference on the ‘implicit learning’ task.

The researchers discuss their results and comment on the possible involvement of the dorsolateral prefrontal cortex and a number of other pathways. They also suggest that implicit memory involves primary motor cortex and supplementary motor areas but it is also interesting to note that the cerebellum is thought to play a significant role in this type of learning for motor tasks. I would be interested to see a larger replication study with clearly delineated primary outcome measures and a range of tasks examining both implicit and explicit memory.

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The paper reviewed here is ‘Beyond the Brain: widespread pathology in Huntington’s Disease’ by van der Burg and colleagues.The article is written by a group from the Swedish Lund Institute Neuronal survival unit and is classed as a ‘personal view’. However there is a small green box towards the end of the article which contains details of the search strategy and selection criteria which thus allows the reader to gain a better understanding of how the article was orginally constructed as well as providing a useful starting point for someone interested in updating the article. The article focuses on non-neuronal aspects of Huntington’s Disease (HD) in keeping with the expression of Huntingtin in such tissues. The article begins with a look at some of the posited functions of the Huntingtin protein which sets the scene for an exploration of non-neuronal manifestations of HD. There is a look at some of the processes that may contribute to weight loss including possible alterations to Insulin processing and adipocytes although much of the work here is in murine models. The potential impact of mutated Huntingtin on gene expression in myocytes, the expression of Huntingtin in cardiac myocytes, possible actions on osteoblasts or osteoclasts and altered immune response are all considered. The authors then return to the question of the cellular basis of these observations before looking at how such a discussion may inform the search for biomarkers and novel therapeutic paradigms. This is a concise review which references 110 papers and thus provides the reader interested in this area with a useful starting point for their investigations.

References

Van der Burg J M M, Bjorkqvist M and Brundin P. Beyond the brain: widespread pathology in Huntington’s Disease. Lancet Neurology. 2009. 8. 765-74.

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Research In Dementia

The researchers found that gamma-secretase, an enzyme implicated in Alzheimer’s Disease pathology binds to a class of  transmembrane proteins known as tetraspanins  (Wakabayashi et al, 2009) as well as to a number of other proteins. The tetraspanins have a number of different functions within the cell and it will be interesting to see how gamma secretase relates to these functions. There is further coverage here.

News In Brief

Experimental evidence has shown that expression of IL-6 in murine brain can lead to removal of amyloid plaque by microglial cells. There has been significant evidence to suggest a role for inflammation in the disease process and these new findings show that the relationship between inflammation and build up of Amyloid Plaques in the brain is complex. In one study there was found to be an association between plasma levels of ABeta42 and risk of conversion from Mild Cognitive Impairment to Alzheimer’s Disease and it will be useful to see further replication of these findings. Levels of a class of transcription factors NFAT’s (Nuclear Factors of Associated T-Cells) was significantly elevated in the hippocampi of subjects with Mild Cognitive Impairment or Alzheimer’s Disease compared to controls and at least one pathway has been suggested between activation by Amyloid plaques and expression of regulated genes.

A study in the BMJ showed an increase in the number of prescriptions of antidepressants from 1993 to 2004 and this was attributed to the use of long term prescriptions. There is further coverage here. In the Proceedings of the National Academy of Sciences there is a paper on the use of a new genome sequencing technology – whole exome sequencing (which focuses on genes coding for proteins rather than the entire genome sequence) in a case which resulted in a rapid diagnosis and it will be interesting to see further developments in this area.

There is also evidence that neighbouring groups of Chimpanzees approach the same problem in different ways which the researchers have interpreted as cultural differences. Such interpretations may have implications for developing models of human culture.

Blogosphere

Over at Science Life there is coverage of the Neuroscience conference in Chicago which amongst other items reports on a talk by Erik Kandel, the genetics of anxiety and neuroscience in social media. October 19-23rd was Open Access week and over at Beta Science, Morgan Langille writes about the use of an open-access website BioTorrents for sharing data and other resources. Over at Medical News Today there is a look at an association between gamma synuclein and depression. Software Advice has an article on iPhone applications for doctors and medical students.

References

Wakabayashi T, Craessaerts K, Bammens L, Bentahir M, Borgions F, Herdewijn P,Staes A, Timmerman E, Vandekerckhove J, Rubinstein E, Boucheix C, Gevaert K, De Strooper B.Nat Cell Biol. 2009 Oct 18. [Epub ahead of print]. Analysis of the gamma-secretase interactome and validation of its association with tetraspanin-enriched microdomains.

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The podcast reviewed here is the October 2009 edition of the American Journal of Psychiatry podcast which is freely available here. I’m not sure if it was the browser i’m using (e.g. the performance of browser specific plug-ins) but the narrator’s voice appeared to me to be fast paced and clipped. A study – the TADS study is discussed. This is a 36-week trial comparing placebo, fluoxetine, CBT or a combination in the treatment of depression in adolescents. The results are complex and discussed in the context of previous trials in this area. There is also a look at the interaction between cluster B traits and suicide. There was a discussion of a curious finding in emotional processing with antidepressants – the researchers in one study found that changes in emotional processing were manifest before changes in mood in response to antidepressant medication. There is also a discussion of binge drinking in middle-aged and older adults. There is a lot of material covered in this podcast, sometimes complex and I found myself listening to parts of it again to gain a better understanding of the material. I found the material to be very informative.

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The article reviewed here is ‘Cognitive Impairment in Multiple Sclerosis: Evidence-based Analysis and Recommendations’ by Jeffrey Rogers and Peter Panegyres. While the review is highly structured, there is no methodology outlined, which might be useful for instance for those wanting to update the review. In the introduction the authors outline some of the associations of cognitive dysfunction in Multiple Sclerosis (MS) including those in the area of employment and rehabilitation. The authors then look at the neuropsychological profile of MS covering processing speed, memory retrieval and attention amongst others. Neuroanatomical considerations are addressed briefly before the authors turn to factors which influence cognitive dysfunction. This was a useful section examining factors such as disease subtype and duration. They then look at screening tools for cognitive dysfunction in MS drawing attention to the performances of the Paced Auditory Serial Addition Task and the Clock Drawing Test. Although there are a number of reviews of cognitive dysfunction in MS and this one is now 2 years old, the subject is sufficiently broad for this to be useful and I found the section on screening to be particularly informative.

References

Jeffrey M Rogers and Peter K Panegyres. Cognitive Impairment in Multiple Sclerosis: Evidence-based analysis and recommendations. Journal of Clinical Neuroscience. 14. 2007. 919-927.

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

The blog reviewed here is ‘Open MRS‘.  Open MRS is an acronym for the Open Medical Record System and is described on the Open MRS website (the main website is found here) as follows:-

‘OpenMRS is a community-developed, open-source, enterprise electronic medical record system platform. We’ve come together to specifically respond to those actively building and managing health systems in the developing world, where AIDS, tuberculosis, and malaria afflict the lives of millions. Our mission is to foster self-sustaining health information technology implementations in these environments through peer mentorship, proactive collaboration, and a code base that equals or surpasses proprietary equivalents‘

The invitation is made to the reader to contribute to this collaborative effort.

Appearance and Design

There is a white background which takes on a graded beige colour towards the title pane region of the page. The articles appear on the left 4/5’s of the page and articles are demarcated by thick blue lines. On the right hand side of the page, the reader can navigate through the site according to categories (‘what people talk about’), RSS feeds for the site, as well as a list of contributors. Previous articles can be accessed at the foot of the page by clicking on the arrow icon which takes the reader to the next page of articles. These have to be clicked through page by page.

Articles

There is no ambiguity here – the articles are highly technical often focusing on the actual code being written within the Open Medical Record System. The blog dates back to October 2005, but the articles start regularly from May 2007. On this page, the author describes the need to create a browser based form for data collection thus outlining a strategic object for the project in a semi-technical language. In an article on this page, Mathew Harrison reviews some useful books for designing open source projects. Vladimir writes his initial thoughts about coding a rule builder for the database. While superficially not sounding particularly interesting to the uninitiated, it is in fact a useful method for giving flexibility to the user in their interactions with the database. The rule builder would enable information to be retrieved from the database and displayed in a specific format. So for instance, they give the example of a list being generated for patients who need their bloods checked that day – logistically speaking this is potentially very useful for a health service. In another post, Matt describes the creation of a layer for allowing mobile phones to access data on the database. With time, more developers are recruited internationally, bringing their skills to bear on the project. Programmer Ime Asangansi joins the project and in an article from April 2nd 2008 describes the modification of an established part of the database interface – Xforms using archetypes. In a June 26th 2008 article the difficulties of correctly identifying patients in the database are discussed and this type of problem recurs in various database applications. At the time of writing version 1.5 of the Open MRS has been released and it is interesting to read about the actions behind the scenes during each part of the development cycle.

Conclusions

This is a highly technical blog about the development of an open source medical database. The blog is interspersed with a number of less technical articles which are able to engage a more general audience. The blog is particularly suited to those with an interest in open source healthcare paradigms as well as those with an interest in health databases. The developers are contributing to a noble cause which hopefully should lead to an improvement in healthcare for people in parts of the world still awaiting highly structured IT healthcare infrastructures with all of their accompanying benefits.

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

The audiobook reviewed here is ‘The Education of Children’ by Alfred Adler. The book is narrated by Robin Lawson who reads expressively and  at a moderate pace. Adler is considered to be one of the founders of psychoanalysis and he has had a profound influence on the subsequent development of psychotherapy and counselling. In this book as the title suggests, he writes about the education of children. I found the work a little surprising. Prior to coming across this title I had not thought of Adler as someone with a particular interest in the education of children although knowing his importance in the development of psychotherapy. Educational psychology on the other hand is a vast subject which comprises multiple domains of knowledge that have been developing over a considerable period of time. Adler’s work consists as with the work of other psychotherapists including Jung, Freud and Winnicott of his ideas and understanding discussed in the context of his experience without obvious recourse to empirical evidence. The book consists of a considerable number of generalisations and in some cases these are followed by educational recommendations from Adler although these same recommendations are now more than 80 years old. I was interested in the book for the insights it gives into Adler’s interpretation of child development. He discusses the concept of the inferiority complex, a concept which has had considerable influence in popular culture. He also discusses the importance of birth order on subsequent psychological development and interestingly there is contemporary research in this area. I found that the book was well narrated, the ideas clearly elaborated on by Adler but that there were many generalisations, the material was over 80 years old and there was an absence of empirical data. The strength of the book is in conveying Adler’s theoretical understanding of psychology as well as giving some insights into Adler’s thinking.

References

Alfred Adler. The Education of Children. Blackstone Audiobooks. Narrated by Robin Lawson. 1991.

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The paper reviewed here is ‘Relationships between 24-hour blood pressures, subcortical ischemic lesions and cognitive impairment’ by Kim and colleageus and freely available here.

In the introduction, the authors give a very interesting overview of the relationship between blood pressure and subcortical lesions. In particular they focus on the nocturnal blood pressure as there is typically a diurnal cycle with a drop in blood pressure during the night – the so-called dipping phenomenon (and hyperdipping depending on the magnitude of the drop). They discuss some of the evidence of risk associations with non-dipping. They also discuss subcortical vascular mild cognitive impairment (SvMCI).

In the study, the researchers compared 24-hour BP values in controls, people with Subcortical Vascular Dementia (SVaD) and people with SvMCI. People with SVaD and SvMCI were recruited from a memory clinic in Seoul, Korea while the controls were recruited from a cardiology centre again in Seoul. I wasn’t clear on how SvMCI was diagnosed and thought it might have been a complex judgement. There are details given in the paper and the authors do acknowledge the difficulties in attributing cognitive impairment to a subcortical vascular cause but they state that other causes have been excluded. Nevertheless the MRI scans in themselves would not be suitable for detecting amyloid plaques that would be present in an AD (although they have looked specifically for other markers of AD pathology on the MRI). Blood pressures were obtained using ambulatory blood pressure monitoring and a 3 Tesla MRI scanner was used for the MRI scans and they use a specific protocol to assess the images for vascular lesions. Cardiovascular risk factors were identified in the participants. The Seoul neuropsychological screening battery was used and a breakdown of this screening instrument is given in the paper. They also state that the

There were a number of exclusion criteria although this didn’t affect the final numbers too much (89 included with SVaD or SvMCI initially and 79 after exclusion). On looking through the methodology and results, I noticed that there were a large number of comparisons being used and the researchers were also using the Tukey’s test – which is used in a post-hoc analysis. The researchers described their main findings as an increased systolic blood pressure variability in the SVaD group compared to the SvMCI group as well as an ‘disruption’ of the nocturnal BP rhythm in the SVaD and SvMCI groups. The researchers themselves note that this is not a prospective study and that the SvMCI diagnosis was made in the ‘absence’ of established criteria for SvMCI. While these were potentially interesting findings, I noted the post-hoc analysis and would be interested to see a larger replication study, prospective in design and using these results to inform the primary outcome measures in the next study.

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

The Neuroscience Information Framework Version 2.0 is now online. The NIF is described as

‘A dynamic inventory of web-based neuroscience resources: data, materials, and tools accessible via any computer connected to the internet‘

The NIF is also described as a National Institute of Health Blueprint for Neuroscience Research initiative (see also this review of a paper on the Neuroscience Information Framework). The NIF Tools include a registry of electronic catalogues of neuroscience resources, a ‘deep web’ resource – the NIF Data Federation, the NIF Web Index – essentially a search tool for neuroscience information on the internet and the NIF vocabulary which includes Neurolex. Neurolex is a neuroscience lexicon which at the time of writing contains 7972 terms. Such a lexicon has implications not just for the ability to find relevant information on the internet but also has potential for facilitating neuroscience dialogue.

A small study of people with Alzheimer’s Disease (AD) compared with people with mild cognitive impairment and healthy controls (n=55) provided evidence that there was a correlation between the PET and CSF markers of ABeta but that they did not correlate significantly with cognitive impairment (Jagust et al, 2009). In a cross-sectional study of symptoms in people with bipolar disorder (n=88) published in the journal of the World Psychiatric Association, the researchers found a significant association between the mixed affective state and negative cognition and hyperactivity (article freely available here).  In a study of people in the Andean highlands in Ecuador (n=167), the researchers used the Spanish version of the Beck Depression Inventory II and identified that the scores on the somatic component of the scale were significantly higher than the cognitive component (article freely available here). The researchers interpreted this as  resulting from the influence of culture on the expression of the depressive illness. There is an interesting article on the National Dementia Research Brain Bank here. A meta-analysis of prospective and case-control studies examining the relationship between smoking and Alzheimer’s Disease which adjusted for a number of factors including tobacco company affiliation of the studies showed that smoking was a significant risk factor for Alzheimer’s Disease (Cataldo et al, 2009). A post-mortem study comparing the brains of people who had Alzheimer’s Disease and hyperphagia with those who did not found a significant reduction in 5HT4 receptors in the former group  (Tsang et al, 2009). In an intracranial electrophysiological study published in Science, the researchers provided evidence that language processing occurs in Broca’s area and is divided into processes for grammar, meaning and articulation with each process being separated by milliseconds.

There is a preliminary report on a new technology which measures electrical signals between the central nervous system and the vestibular apparatus in the ear. The Australian research team state that they are able to characterise responses in a number of central nervous system disorders and they include depression. There is a website which details the technology and which also contains a link to a promotional video. Using Medline, I was able to find 5 studies including 1 on schizophrenia and 1 on depression, although both had small sample sizes they provided data on the application of the technology. It will be interesting to see  further published data with larger sample sizes as this becomes available. Researchers have provided indirect evidence that Macaque monkeys experience the ‘Uncanny Valley‘ effect. This effect describes the tendency for people, or monkeys in this case, to become uncomfortable if computer simulations of members of their species are too realistic. The finding in monkeys suggests an evolutionary basis for this effect. It will be interesting to see if this has implications for social bonding.

Blogosphere

The Neurocritic has an interesting article on ‘Neurocinema Neurocinematics’ here. Professor Charlton has an interesting post on science here.

References

Cataldo JK, Prochaska JJ, Glantz SA.J Alzheimers Dis. 2009 Oct 8. [Epub ahead of print]. Cigarette Smoking is a Risk Factor for Alzheimer’s Disease: An Analysis Controlling for Tobacco Industry Affiliation.

Jagust WJ, Landau SM, Shaw LM, Trojanowski JQ, Koeppe RA, Reiman EM, Foster NL, Petersen RC, Weiner MW, Price JC, Mathis CA; Alzheimer’s Disease Neuroimaging Initiative. Neurology. 2009 Oct 13;73(15):1193-9. Relationships between biomarkers in aging and dementia.

Tsang SW, Keene J, Hope T, Spence I, Francis PT, Wong PT, Chen CP, Lai MK. J Neurol Sci. 2009 Oct 7. [Epub ahead of print]. A serotoninergic basis for hyperphagic eating changes in Alzheimer’s disease.

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In the 15th October 2009 edition of the Nature Podcast there is a look at a study of Colombian Guerillas who learnt to read in adulthood. This was a structural study (although I wasn’t sure if this was a structural MRI study) comparing the guerillas with people who learnt to read in childhood. The team wanted to learn if there were any differences between the two groups in terms of brain structure. Triangulating with the abstract in the Nature paper, the researchers found differences in the angular gyrus, interhemispheric connections and dorsal occipital gyri amongst others. They also suggest that the Angular Gyrus modulates information in the dorsal occipital gyrus although I wasn’t clear on how this was inferred from the structural  data (a post-mortem study might infer this from the directionality of individual synaptic connections). In the 8th October edition of the Nature Podcast, there is a look at a study of personal genotyping in two companies which found differences in the results between the two which the researchers attributed to the use of different gene markers. There is also a discussion of some of the recommendations for such testing. They also report on a genetics conference in Honolulu in which genome wide association studies and linkage analyses in 1000 autism families finding a significant association with a region on chromosome 5. In the 1st October 2009 podcast there is a brief report on a study in people with partial cortical blindness who were presented with faces and who developed examples of physiological mimicry (e.g. muscle twitching in the relevant areas). This has implications for the pathways involved in emotional processing and also the level at which it is undertaken (i.e. conscious versus unconscious).

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The blog reviewed here is the ‘Medical Ethics Blog‘. The blog is about medical ethics as the name suggests and is written by Stuart Laidlaw, a journalist at the Toronto Star (to which the blog is affiliated) and book author.

Appearance and Design

The title pane contains references to the Star and links to other sites on the Star’s website. The blog has a central white pane with cyan panes on the left and right hand side. The articles are written on the right-hand 2/3’s of the central pane and are displayed with black text on a white background. On the left hand side of the central pane, there are numerous links including articles archived by month, links to other relevant sites and article categories.

Articles

The blog starts with the first article listed under May 6th 2008. In this article, he looks at Medical Tourism, a theme which is developed through the blog. In this article, he looks at Wal-Mart’s move into healthcare. This article looks at medical blogs and this one at reporting on drug trials. The interaction between religious beliefs and refusal of treatment is discussed in this article. This article looks at a considered amendment to a UK government bill to enable tissue to be removed from people lacking capacity to be used in research and the story continues to covered in this article,  this article and this article. The ethics of genetic testing for children are covered in an article in which a company makes claims about prediction. This article looks at american Senator Charles Grassley’s investigation into Pharma ghostwriting and states that company executives thought up titles for articles and then employed ghostwriters to draft the articles. I found this article on a fake submission to an online journal quite interesting as the issue of trust between authors and editors appears. This very issue of trust is surely interesting from a sociological perspective as it shows the type of  ’relationship’ issues that influence science away from the theory and must be factored into a ‘comprehensive’ model of science. I was also quite interested to see a debate generated across the newspapers (?news sphere) in Canada about these issues in a similar way to the debates that are generated across the blogosphere. There is a discussion here of whether academic fraud should be criminalised. Laidlaw also looks at the Canadian Journal of Medicine’s decision to make reporting of conflicts of interest for authors more stringent.

Conclusions

I was impressed by Laidlaw’s willingness to tackle very controversial areas. Laidlaw presents difficult issues that are in need of wider debate and I sensed that the blog has gathered momentum in terms of the rate at which articles are produced as well as the nature of the issues that are discussed. There are also a number of articles discussing issues relevant to psychiatry.

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The audio book reviewed here is Dr John Sarno’s ‘The Divided Mind’ narrated by Paul Hecht and John Boles. I didn’t realise there were two narrators until checking the credentials after listening to the book! In any case, I found it clearly narrated and well paced. The material in the book is quite complex and would repay close study for the reader interested in psychosomatic medicine. Sarno originally trained in general medicine and at his website is described as a Professor of Rehabilitation Medicine. I found it difficult to draw conclusions about the material in the book as I think it requires considerable reading around the subject but found it very interesting. Sarno develops some of the underlying theory of Alfred Adler and Sigmund Freud. He maintains that there are a number of mind-body disorders and refers to Adler’s description of the brain giving rise to physical symptoms. Indeed he quotes from Adler who discusses possible mechanisms by which the brain can produce effects on the body. This appears to be the basis for psychoneuroimmunology and he refers to Professor Candice Pert’s work on the ‘Molecules of Emotion’ (see review here). He distinguishes between Freud and Adler in that he states that Freud did not consider the notion that bodily symptoms could arise from the brain for the purposes of ‘distracting’ the brain (or mind) from distressing emotions. Through his work Sarno suggests that these emotions include rage and gives clear examples where anger is controlled at the conscious level only to emerge in symptoms. I wasn’t clear on the abbreviation TMS in the book and only realised it was Tension Myositis Syndrome on looking elsewhere. Sarno’s arguments are logically developed and seem to me intuitively valid. However a quick search of Medline using the keyword ‘Tension Myositis Syndrome’ resulted in four references with one being a 2007 study by Schechter and colleagues. Such a search may not produce all of the relevant studies although it would be useful to see further formal evidence to support both the diagnosis and the treatment efficacy.

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The paper reviewed here is ‘Mobile and Fixed Computer Use by Doctors and Nurses on Hospital Wards: Multi-method Study on the Relationships Between Clinician Role, Clinical Task, and Device Choice’ by Andersen and colleagues and freely available here. In the abstract the authors draw a number of conclusions including the following

‘Nurses’ work, and clinical tasks performed by doctors during ward rounds, require highly mobile computer devices‘

as well as

‘In selecting hardware devices, consideration should be given to who will be using the devices, the nature of their work and the physical layout of the ward‘

The researchers aims were stated as answering the following

‘(1) which device is used by whom, where, for which clinical task, and in collaboration with whom? and (2) what impact does the design of the device have on its use on hospital wards?‘

The researchers used a complex design for the study which involved direct observation of staff during task completion as well as questionnaires and assessment of the hardware devices (assessed with the usability criteria listed here).  The study was set in 2 geriatric wards in Sydney. It could be argued that these results are generalisable but also that the study’s findings are restricted to this particular type of service (i.e Australian geriatric wards). In favour of the latter, in some services configurations ward rounds may be conducted in one place in which case stationary computers would have benefits over mobile devices with the former typically having more resources per unit cost. Devices included desktop PC’s and devices on wheels as well as tablet PC’s.

The study was conducted over an 18-day period and included doctors and nurses with an average of just under 3-years experience on the study ward. It would have been interesting to see the results if staff had been stratified according to the number of years experience on the ward and it would have been particularly interesting to see the results in those with the most experience (although experience may influence the roles). The observational data collection took place between 7am and 4pm. A number of details were recorded in the study and the clinical tasks documented are listed in Table 1. The authors also include a schematic diagram of the wards illustrating the placement of some of the computers.

Given the nature and amount of data that was collected, there are numerous results in both quantitative and qualitative formats. In terms of the observed tasks, I found the following particularly interesting

‘The most frequently observed tasks were administering drugs (31.4%), preparing drugs (27.9%), and reviewing a patient’s chart (15.4%)‘

Nurses were predominantly using computers-on-wheels for their tasks particularly in conjunction with medication administration. Just under 40% of the doctors were using tablet PC’s – mainly to ‘review charts and view results’. Furthermore the doctors weren’t using the tablet PC’s when not on the ward round. In the questionnaires, several of the staff said they had not received training in using devices such as the tablet PC’s. This raises the important issue of how much these results are dependent on the training staff receive and how much training would have influenced the results reported here.

The researchers have been creative in the design of this study, trying to encapsulate the use of mobile and desktop computers in a hospital ward using a combination of quantitative and qualitative methodology. The study highlights some of the important factors that determine the success of such technology. These factors include the functions of the service, the types of devices, the functions for which those devices are being used, the software that is being used for those devices (although the operating system was specified, the individual software programs were not discussed in detail) and the training for both the software and the devices.

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The paper reviewed here is ‘Striosomes and Mood Dysfunction in Huntington’s Disease’ by Tippett and colleagues and freely available here. The authors write in their abstract that

‘we report here a significant association between pronounced mood dysfunction in Huntington’s Disease patients and differential loss of the GABAa receptor marker in striosomes of the striatum‘

In the introduction, the authors describe the importance of the GABAergic projection neurons in the striatum in the pathogenesis of Huntington’s Disease (HD) as well as noting the initial involvement of those neurons that project to the external pallidum.

In order to arrive at the above conclusions, the researchers compared 35 people with Huntington’s Disease with 13 control cases. This was a post-mortem study, retrospective in nature. The preparation of brains is described in the methodology section and the researchers state that the pathological grading was conducted by a pathologist with expertise in HD. For subjects with HD, the number of CAG repeats (associated with disease severity) in the gene region was assessed. The staining method for the specimens is then described.

As this is a retrospective study and the researchers were interested in correlating clinical features with pathological findings they required an instrument that was capable of capturing clinical features retrospectively. For this purpose they designed questionnaire for assessing motor,  mood and cognitive components of the disease. The details surrounding the construction of this questionnaire are given in the supplementary material. The questionnaire is administered to family members who recall information retrospectively. They validated this questionnaire by testing it in a family with HD who had also undergone testing on other clinical measures including the HADS for depression and anxiety.

Pathological specimens were divided into predominantly striatal loss, predominantly matrix or loss or a mixture of both. The researchers reported that ‘mood dysfunction indices again were significantly higher in the striosome-damaged group at clinical onset’. The striosome damage in this case refers to the loss of GABAa receptor immunostaining in these regions.  Although the CAG repeat correlations reproduced some previously well-established findings, the researchers also found that the average number of CAG repeats was significantly lower in the striosome-damaged group and further that the striosome-damaged group had a later-onset of disease.

This is a difficult paper to read as it covers a number of specialised areas including in particular the preparation and assessment of the pathological specimens. Nevertheless multidisciplinary studies of this type are essential in gaining a better understanding of the illness and correlating pathology with certain clinical features. I didn’t understand the finer points of the preparation of the specimens. I would argue though that striatal loss should be a continuous rather than discrete process and for the purposes of data-analysis there were three groupings (e.g. predominantly striatal loss). However, when it came to the assessment of clinical features, I think it’s not unreasonable to say that there are obvious methodological difficulties with retrospective assessment of clinical features particularly as in Huntington’s Disease they manifest in several different areas including motor functions and cognition. There are well established measures for assessment of motor function in HD in living patients and a prospective design would be much better placed to test the hypothesis generated in the study. In such a design, clinical measures would be repeated at intervals and the most recent could be used in any post-mortem correlational analysis. In this study, one obvious objection would be a recall bias by informants in favour of their understanding of how the disease progresses. This might not tally up with the actual disease progression. However the researchers support their use of this method by the inclusion of a validation study in the supplemental material in a family with HD although even here large replication studies would improve confidence.

The study has generated a number of testable hypotheses. Furthermore these hypotheses place the structure of the striatum squarely in the centre of they hypothesis.

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The article reviewed here is ‘Beyond Mild Cognitive Impairment: Vascular Cognitive Impairment, No Dementia VCIND’ by Stephan and colleagues and freely available here. The abstract reads

‘The concept of vascular cognitive impairment (VCI) has been introduced to describe the spectrum of cognitive change related to vascular causes from early cognitive decline to dementia……………….However very little is known regarding the mildest stage of VCI, generally termed ‘vascular cognitive impairment, no dementia (VCIND)‘

and puts the aim of this paper into perspective.  The review contains no explicitly stated methodology but is divided into seven main sections. The role of vascular disease in ageing of the brain including atrophy is discussed briefly. The authors then look at classification schemes. The importance of Mild Cognitive Impairment (MCI) as a category is discussed as is the associations of vascular risk factors with MCI. The authors then distinguish between the broader term vascular cognitive impairment (VCI) and the more restricted use of the term MCI. The authors emphasise the current difficulties with VCIND as refinements in the diagnostic criteria are still needed and also look at the relationship of VCIND to dementia.  The ambiguity in this relationship makes it more difficult to make the case for a boundary between VCIND and MCI at the current time. The boundary issue however is the subject of the next section and the authors provide neuropsychological, neuropathological and neuroimaging evidence of differences between MCI with and without vascular pathology although the picture is less than straightforward. The authors then focus on the evidence for minimising vascular risk factors for progression to dementia. They suggest that there is relatively little evidence that this prevents MCI or improving MCI if it is already present although adding that modifying vascular risk factors is effective in reducing risk of hypertension and strokes. They conclude by identifying a need for further understanding in this area. The concept of VCIND is relatively young and it will be interesting to see how this develops.

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

I’ve recently started using Twitter. For those not familiar with Twitter, it can be thought of as the SMS of the internet. On opening an account you can enter text into a dialogue box and send it out to the twitter  stream. In other words you can send out your words to the twitter audience, but there is a limit of 140 characters. The reason i’m mentioning this is because I’ve been finding that it has lots of useful applications in keeping up to date. Many organisations including the NHS and the Royal College of Psychiatrists as well as journals and people with an interest in psychology, psychotherapy, pharmacology and neuroscience send out relevant tweets. Although many people have been using twitter to discuss more general issues or ‘chat’ online, twitter also facilitates exchange of current, relevant and useful information on specialised interests. The nature of the medium means that it becomes very easy to discuss the items with each other as well in a free flowing dialogue only a little different to being together in the same room. Here i’ve included a few of these items which I discovered on Twitter and want to thank my fellow Twitterers for providing a lot of useful information.

The American Psychoanalytic Association has developed a diagnostic manual. To quote from their website

‘It systematically describes:

Healthy and disordered personality functioning

Individual profiles of mental functioning, including patterns of relating comprehending and expressing feelings, coping with stress and anxiety, observing one’s own emotions and behaviours, and forming moral judgments

Symptom patterns, including differences in each individual’s personal or subjective experience of his or her symptoms‘

This is a fascinating development and looking at the above, it seems as though the manual relates just as much to healthy functioning as it does to illness. It will be interesting to see how the use of this manual becomes integrated into clinical practice and the relationship of this manual to ICD-10/11 and DSM-IV/V.  An American study provided evidence of the cost-effectiveness of telephone-based Cognitive Behavioural Therapy for depression in primary care (covered here and here) although the application of these results will depend on local protocols and service structure. The study is in the Archives of General Psychiatry. Aaron Beck who developed CBT was awarded the Lasker prize for clinical research.

A prospective California study with 9000 subjects provided evidence of an association between higher levels of cholesterols in people aged in their 40’s and the subsequent prevalence of Alzheimer’s Disease in their 60’s to 80’s. The article is freely available here. Analysis of the data from the Nun study continues with over 500 brains obtained post-mortem. The Nun study followed up several hundred nuns, examining a large number of factors and identifying associations with Alzheimer’s Disease. In this article you can watch an interesting video containing interviews with some of the nuns as well as a post-mortem dissection of a brain with enlarged ventricles. The Nuns have been very generous in ensuring that their brains can be used for research after their death and this type of research is very important in coming to a better understanding of the disease process. A study has provided evidence of a possible association between a virus XRV and Chronic Fatigue Syndrome. In a study of people with Parkinson’s disease using a driving simulator and comparing this group to age-matched controls, the Parkinson’s subjects were significantly more likely to experience a crash under low visibility settings than the control group. There were a number of factors including visual processing speed which were significantly associated with driving performance in the simulator. A phase 1 clinical trial is currently underway to examine the potential neuroprotective role of the antibiotic Minocycline in acute ischaemic stroke.

A prospective study involving 10,094 subjects over 4 years looked at adherence to a Mediterranean diet and new-onset depression and found evidence of an inverse relationship between increasing adherence to the diet and incidence of new-onset depression. A conference on empathy took place at the end of September 2009 and the conference website can be found here. There is an estimate from one study that each person has roughly 100 new mutations in their genome based on an analysis of the difference in genes in two chinese men who shared an ancestor at the beginning of the nineteenth century. A 1 Billion dollar Japanese project to create a supercomputer which will amongst it’s many functions will aim to simulate life is currently underway and is covered here. An fMRI study in monkeys and humans provided evidence of activation of the inferior Parietal lobe in humans alone when watching tool-using activities. There were a number of other areas that were activated in both humans and monkeys when undertaking this task.

The Natural Health Service is an ambitious project being undertaken in the NHS to plant 1.3 million trees which should reduce the carbon footprint of the NHS.

Health 2.0

There is an article here looking at how medical doctors are making use of social media. This article looks at Scientists on Twitter.

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Today is World Mental Health Day.  The World Mental Health Day was started by the World Federation for Mental Health in 1992. The World Federation for Mental Health was set up in 1948 and their mission statement can be found here and includes the following:-

‘WFMH is an international membership organization founded in 1948 to advance, among all peoples and nations, the prevention of mental and emotional disorders, the proper treatment and care of those with such disorders, and the promotion of mental health‘

Their website contains more information on World Mental Health Day here. The theme for this year’s campaign is

‘Mental Health in Primary Care: Enhancing Treatment and Promoting Mental Health‘

A Google news search highlights examples of the recognition of World Mental Health Day including amongst others  Australia, Bahrain, Bulgaria, China, India, Northern Ireland, Pakistan, South Africa and Sri Lanka, The BBC have coverage here and are holding several ‘headroom’ events. In the blogosphere, World Mental Health Day is also covered in the London 2012 blog, Dr Deb’s blog, the Reach Out blog, Dr Samir Parikh’s blog amongst others. Just 17 years on and it can be seen from the above that the World Mental Health Day is already very successful.

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The podcast reviewed here is an Acta Scandinavica Psychiatrica interview with Professor Sir David Goldberg who recently received a lifetime award from the Royal College of Psychiatrists (see here and here) (also see here for a list of 10 books he recommends). This might be more properly considered as a video (which it is) and this is a fascinating interview with a psychiatrist who has made valuable contributions in many different areas. Aubrey Lewis is one of the prominent historical figures in British Psychiatry and there are many insights into his views and practices in this interview. We here his views on the General Health Questionnaire which he developed and which has gone on to become extremely successful being used across the world. We hear Sir Goldberg’s views on a number of clinical issues and there are many example of his wisdom:-

‘you listen not just to what the patient is saying, you listen to the music in their voice….it’s just as informative as listening to the heart sounds‘

He also discusses the book he has written with Ian Goodyear – ‘The Origin and Course of Common Mental Disorders’. While the interview is approximately 30 minutes long it contains many deep insights into psychiatry and provides an opportunity to learn more about Professor Sir David Goldberg and his work.

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The blog reviewed here is ‘Fierce Mobile Healthcare‘. I call it a blog, although it could also be considered as a series of news articles on mobile healthcare technology. This blog is linked in with a number of other IT healthcare blogs and this is a fast emerging area of importance.

Design

The blog contains a white background with articles written in black text on a white background. There is a white and blue title pane which links to other blogs in the series. There are links on the right hand pane to a free newsletter, white papers and events. The left hand pane contains references to press releases, popular topics and recent comments. At the time of writing there are also a number of adverts displayed. There is also a search bar and the reader can see the most e-mailed comments. In order to identify the archived news stories, the reader must click on the more button which brings up a longer list of news items as well as an index at the bottom of the page which orders the articles into pages.

Content

The articles date back to April 28th 2009. The immediately displayed post is a summary of the article. The reader needs to click on a link at the bottom of the page to get to the main article or associated press release.  Indeed this first article is about an award for a very useful piece of mobile healthcare software. I was quite surprised to read that in large scale disease surveillance studies that

‘health workers carried hundreds of thousands of sheets of paper to the field, a process that was inconvenient, expensive and environmentally unsound‘

The software in question, esurveyor, is an open source design (meaning the code is transparent, freely available and developed by a collaborative community) and has improved the efficiency of the data collection process as well as being the most widely used healthcare software for mobile devices. This technology when used in combination with the relevant hardware has enabled a number of organisations in sub-saharan countries in Africa to collect public health data which is then used to inform policy. Articles that I found interesting included the following

Use of a mobile communication system in an Accident Emergency system including devices which could be disinfected

New mobile healthcare technologies including software that analyses text messages to assess the owner’s mood

Using RFID to track hospital equipment covered in this article

An article on technology for older adults nicknamed nana technology (see also this article)

Appointment of an executive director at the UCLA Wireless Health Institute

A Florida trial of patient mobile touchscreen devices with multiple functions

The potential of mobile technology to change nursing practice

GPS Shoes to track people with Alzheimer’s Disease

Through several links – this article on 140 potential uses of Twitter in healthcare

Link to an interview with Jay Parkinson on the impact of internet technologies on health

Wireless Body Area Networks for detecting falls in older adults in the home

Article about a mobile screening tool for depression

Healthwear facilitating early hospital discharge

Article about a US insurance company backing telehealth care

Article on medical students use of mobile technology

Conclusions

This is a fairly specialised ‘blog’ with detailed news updates on emerging mobile healthcare technologies and trends.

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The audiobook reviewed here is ‘Linked. Unabridged’ by Albert-Laszlo Barabasi and narrated by Henry Leyva. The narration is clear and I thought engaging particulary as this is a book about mathematical concepts. To elaborate on this, the book is about the mathematics of networks although it is geared to the general audience and does not feature any explicit mathematical formulas which if included would be complicated due to the nature of the medium. Barabasi instead takes the reader straight to the implications of the maths in terms that are meaningful. He takes us through the lives of several mathematicians and physicists  leading up to the important discoveries in the mathematics of networks. In this regards he talks about the findings that were reported before but related to the commonly used term ’six degrees of separation’ which suggests that each of us is linked to everyone else by a maximum of six links. Two important concepts are discussed in the formation of networks – the fitness of nodes and the duration of time with the earlier nodes building more links and these are brought to life in the examples that he gives. I had read a previous book by Malcolm Gladwell – The Tipping Point – a number of years ago and was interested in the concept of connectors – people who have many connections with other people. Gladwell also wrote the book ‘Outliers’ (see review here) and I found some familiar themes taken up from this book including another look at connectors but this time from a mathematical perspective. The curious point that Barabasi made was that the same mathematical laws applied to very different systems from the way genes in Bipolar Disorder operate within networks or key genes in multiple organisms also operate in networks (e.g. some of the most ancient genes form the hubs of intracellular chemical networks in multicellular organisms) to the spread of infectious disease in the population, the growth of the internet and citations in the scientific literature. Barabasi has teamed up with scientists from many disciplines and produced many interesting and varied findings in the process. Barabasi also has the ability to convey this to the reader*.

*It would be interesting to see in what other ways these laws might applied to mental illness.

References

Albert Laszlo Barabasi. Linked. 2002. Narrated by Henry Leyva. Random House Audible.

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The article reviewed here is ‘The Genetic Epidemiology of Neurodegenerative Disease’ by Bartram and Tanzi and freely available here. This is a shortish review article without stated methodology which covers some of the main neurodegenerative disease – Alzheimer’s Disease, Parkinson’s Disease, Lewy Body Dementia, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Huntington Disease and Prion Disease. In the introduction, the authors cover issues including the hypothesis that common gene variants CNV’s contribute significantly to common diseases. They also look at the difficulties associated with interpreting small genetics studies

‘Additional, and commonly cited, problems in finding complex disease genes beyond the most obvious are multiple testing, publication bias, and questionable replication‘

and further that

‘In the case of multiple conflicting reports, metaanalysis across all published studies and/or the evidence for a biochemical/functional consequence of the putative risk allele can help distinguish real disease genes from their harmless counterparts‘

Firstly the authors look at Alzheimer’s Disease (AD) and note the contrast between the genetics of early and late-onset Alzheimer’s Disease. The article covers the well documented associations with early onset AD and also the ApoE4 association with late-onset AD. As this is a 2005 article they will not have been aware of the more recent findings regarding the CLU, PICALM and CR1 genes although the other findings are just as valid today as when the article was first written and the authors provide a concise overview. In the second section on Parkinson’s Disease, the authors contrast the relative success in identifying genes in the early-onset form of Parkinson’s Disease (Parkin genes and Alpha-Synuclein genes) with that in late-onset Parkinson’s Disease.

In the next section they focus on LBD and look at alpha-synuclein, while in the section on Frontotemporal Dementia they focus prominently on the established link with Microtubule Associated Protein Tau. In the section on Amyotrophic Lateral Sclerosis they look at the associations with MAPT (as in FTD), Superoxide Dismutase 1 and ALS2. When considering Huntington’s Disease, they note the importance of the Huntingtin gene as well as a number of gene associations which are thought to influence the onset of the disease. In the section on Prion diseases they look at the PRN gene and the ramifications of various mutations of this gene. While this is four years old, it gives a useful overview of gene studies in the neurodegenerative diseases which can be supplemented by more recent reviews in the area(s) of interest.

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The article reviewed here is an open-access article ‘Differential Cognitive Impairment for Diverse Forms of Multiple Sclerosis’ by Gonzalez-Rosa et al and freely available here.  In the abstract, the authors write that

‘The present results suggest a cognitive impairment in the information processing in all of these patients…..This suggests a silent deterioration of cognitive skills for the BMS [Benign Multiple Sclerosis] that is not usually treated with pharmacological or neuropsychological therapy‘

The main question that can be asked here is how do the results, analysis and discussion in the article fit with the above conclusions?

Firstly the researchers have recruited two groups of Multiple Sclerosis subjects. One group has the relapsing-remitting form of Multiple Sclerosis characterised by periods of deterioration and then improvement while the other have received a diagnosis of ‘Benign Multiple Sclerosis (BMS)’ (see Appendix for link to another study on Benign Multiple Sclerosis). I wasn’t clear on how the diagnosis of Benign Multiple Sclerosis had been arrived at. I could not find an explicit reference to the sampling method for the three subject groups and I note that the sample sizes are relatively small with 45 subjects included in the study.

The Posner paradigm was used. This involves a visual display which shows an arrow. A target appears on the screen at the location of either the valid position (indicated by an arrow on the screen) or the invalid position and the subject has to respond by pressing the appropriate button. Both the accuracy and speed of responses are measured and both right and left hands are used which I assume is to avoid any bias from handedness. The underlying assumptions for this paradigm are that it taps into attentional mechanisms – disengagement from gaze target, movement to new target and engagement with new target. They also presented the subjects with standard stimuli and measured the evoked potentials in 4 leads.

Figure 1 shows a comparison of the measures for the invalid and valid trials. The confidence intervals for all of the pairings appear to overlap suggesting that amongst the many possibilities there could be no significant difference between the means. In other words the distinction between valid and invalid trials wasn’t particularly interesting.  Figure 2 shows the Evoked Response Potentials in the four leads in the different groups and the authors note the lack of a certain response – the N1 response in both MS groups. Figure 3 shows a 3d scatterplot of the three subject groups on axes denoting amplitude of frontal N1, response time and latency P300. The three groups are separated into clusters and although I found it difficult to judge the locations of the clusters from the diagram, it appears that the benign MS groups values lie further from the control group than the relapsing-remitting group. This apparent relationship from the visual inspection of the scatterplot also appears to hold for both % of correct responses with the RRMS and controls appearing closer to each other than the BMS group to either. The same holds for the reaction times and this suggests the importance of understanding the methodology of the selection of subjects for the study.

Nevertheless when the researchers performed an ANOVA on the comparisons they found that the control group responded significantly faster than either the RRMS or BS groups. They also found that the valid reaction times were significantly faster than the invalid reaction times using this analysis. Although there were interesting findings in terms of the evoked potentials, the authors draw conclusions about the cognition. In terms of the conclusions given in the abstract it can be stipulated that they researchers have demonstrated a significantly worse performance on a very specific task which involves focusing on a simple visual cue and responding to a visual target that appears on the screen. The magnitude of the increase in reaction times for the BMS group is somewhere in the region of an extra 50ms and so in this study at least it can be argued to be of significance. It would be interesting to see a larger replication study with use of additional psychometric tests.

Appendix

Article on Benign Multiple Sclerosis by Hawkins and McDonnell, 1999.

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The paper reviewed here is ‘Autophagy in Neurodegeneration and Development’ by Winslow and Rubinsztein and freely available here. As the title suggests, the authors discuss the role of autophagy in neurodevelopment and neurodegeneration. As in a number of other review articles that have been discussed here, there is no stated methodology although such articles represent an effective method of communicating important areas that have been selected based on the authors expertise. The paper is divided into 9 sections. In the first section the authors introduce the reader to the two main degradation pathways for proteins in the cell – the specific ubiquitin-proteosome pathway and the non-specific autophagy-lysosome pathway. In the second section they examine Yeast studies. I was intrigued to read that autophagy is induced during periods of starvation in Yeast. The authors summarise the main steps in autophagy that have been identified from Yeast studies. In the third section, the role of autophagy in development and health is examined and again the authors show the important role that autophagy plays in the stress response and deficiencies in components of the pathway can lead to neurodegeneration through the build up of proteins and the lack of nutrients derived from amino-acids. In the fourth section, the authors look at the interactions with other cellular processes and the impact this can have on autophagy proposing that

‘A number of diseases have been shown to manifest a deficiency in autophagy, identifying autophagy as an important secondary disease mechanism‘

In the fifth section, the motor function of dynein in autophagy is discussed as well as the association of under or over-representation of dynein with neurodegeneration which is possibly mediated through impaired autophagy. In the sixth section, the endosomal sorting complexes required for transport (ESCRT for short) are discussed including their association with Frontotemporal Dementia and their role in the processing of integral membrane proteins. In the seventh section, the role of the lysosome in degrading the cargo of the autophagosomes is examined as well as the pathological accumulation of autophagosomes. In the eighth section, there is a look at potential therapeutic interventions aimed at the autophagy pathway and in this regards they consider Rapamycin and intriguingly also Lithium as well as Carbamezapine and Valproate before concluding in the final section that

‘With its implicated roles ranging from viral infection and cancer to liver and cardiac disease.. autophagy’s importance in the maintenance of health is just beginning to be realised‘

The authors have written a review which is elegant in its simplicity and efficacy in communicating the significance of complex cellular processes with many pieces of the ‘jigsaw’ still missing. The authors have also shown the potential relevance of this system to a number of neurodegenerative processes.

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An in-vivo study has provided evidence that Dimebolin has a high affinity for the Serotonin 5HT6 receptor in vivo (Schaffhauser et al, 2009). Dimebolin under the name Dimebon was trialled in Alzheimer’s Disease and showed promising results. There may be a focus on this receptor for therapeutics if these results are replicated.  In this article, there is coverage of a prospective cohort study in Honolulu which includes post-mortems to clarify the processes leading to the dementia. The study has been going on for many decades and the researchers have now accumulated data from close to 800 autopsies and are able to compare this with neuropsychological and other data. NHS Choices discuss a study involving Olive Oil and finding that it binds to A Beta-derived diffusible ligands (ADDLs) and influences in turn their binding to synapses which may have implications for the disease process in Alzheimer’s Disease. In America, a group of neurologists have developed consensus guidelines for the use of cognitive enhancers in adults without dementia. Another study involved contacting retired American Football (NFL) players and conducting a survey over the phone. The researchers found a much higher prevalence of dementia in the NFL players than the national average.

There has been a relative large study comparing people with Tourette’s and OCD with healthy controls and finding no significant evidence of the former conditions with Streptococcal throat infection. There is contrary evidence which suggests that Strep throat infections can be associated with autoimmune processes which involve the central nervous system and these are termed PANDAS.

Scientific American have coverage of some studies supporting the hypothesis that long term relationships foster creativity. In the studies they contrasted analytical with creative thinking. The types of relationships considered were tested indirectly by the use of imagination or by presentation of words with subtle meanings related to the paradigm. However it could be argued that the relationship status of the subject would provide more convincing evidence. Steve Peters, psychiatrist and coach for the Olympic Cyclists is appearing on a television program to work with members of the public to improve their fitness. In this article that covers the story, Steve Peters discusses some of the underlying theory he uses (which appears to relate to evolutionary psychology). An anthropological study looked at old world monkeys and found that increasing neocortical size was associated with the ability to form large social networks.

References

Schaffhauser H et al. Dimebolin is a 5-HT6 antagonist with acute cognition enhanching activities. Biochemical Pharmacology. Vol 78. Issue 8. pp 1035-42. 2009.

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The podcast reviewed here is one of the UCLA Psychiatry Grand Rounds podcast series titled ‘Bringing Psychology’s ‘Positive Psychology’ into Psychiatry’ and freely available here. This is a video of a presentation by Professor Vaillante who has undertaken considerable research into the recovery process from several illnesses including schizophrenia. In this talk, Professor Vaillante examines ‘positive emotions’ and at the beginning of the talk he mentions provocatively the active ingredients of a treatment of ‘faith, hope and love’ in contrast with the psychodynamic exploration of feelings such as anger, guilt and shame.  The talk covers a broad range of topics which fit under the theme of ‘positive emotions’. I was interested to hear Vaillante talk about Autism as a disorder of attachment. He takes a look at the Limbic System and raises the possibility that this may have distinguished the dinosaurs from the mammals with the former group facing a mass extinction. Could emotions have played a role? (However there are a number of alternative hypotheses to explain this extinction which have taken centre stage). He also takes a look at the Insular Cortex (see here for the beginnings of a model on the Insular Cortex) including the Spindle cells and Mirror Neurons. Indeed he notes the much discussed hypothesised relationship to empathy. Vaillante brings together a number of findings including those from recent studies, encouraging the audience to examine possible connections and reappraise the role of ‘positive emotions’.

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The blog reviewed here is the ‘New Media Medicine‘ blog.

Appearance and Functionality

The blog has a professional look, with photographs used in the title pane and articles at the time of writing. The articles are written on a white background and the articles themselves appear over a grey background. There are tabs underneath the title pane – home, e-Learning, web design, forum, blogs and videos. At the time of writing, I found a number of videos under the video heading. Those listed included lectures on integrated biology. The articles in this blog are indexed according to time period and category and these links are found on the right hand pane.

Purpose

The about section is here and describes the founders of the site. Dr Paton has another blog on health informatics (reviewed here). There are also a number of colloborators. The blog is associated with an online medical community.

Articles

The blog begins with this introductory article which explains that it will update the reader on new media medicine. Articles I thought interesting

This article on RFID looks at how these devices are being used to track patients (see this review here for another paper on this subject)

This article links to medical Podcasts

This article links to a video of one of the originators of ARPANET, the precursor to the modern internet

This article links to free health software for mobile devices

This article looks at a text-messaging service for making appointments

This article links to a site about Doctors Gadgets

Summary

The posts are very brief but usually contain links to valuable resources on the internet. I found these links very useful and some were not only working 2 or 3 years after they were included there, but the sites themselves had developed. The reason I mention this is because links can become broken reasonably quickly depending on the sites that are pointed to which gives blogs a transient edge to them.  I’ll probably be making use of some of these resources myself. It’s a pity there are currently no posts after 2007. Maybe it will be updated in the future with more valuable links.

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The audiobook reviewed here is ‘Outliers’ written and read by Malcolm Gladwell. Gladwell is a journalist and established author who has had success with books such as ‘Tipping Point’ and ‘Blink’. Regarding the narration, Gladwell speaks slowly, clearly and persuasively through the audio. Turning to the content, Gladwell looks at the effects of ‘cultural legacy’ on success. In essence he is helping to answer a question about the influence of the environment in shaping our lives. The outliers in the title refers to people who lie outside the two standard deviations of the population and who have attained extraordinairy success. As in other popular science books that have emerged recently, Gladwell develops the theme of the 10,000 hours needed to attain expertise in a subject ( Indeed in medicine, changes to the working conditions of junior doctors has reduced the number of available hours for training and this has provoked considerable debate). His interpretation of the success of the Beatles will surprise some. He argues that not only is a considerable amount of hard work required to develop success, but also the right opportunities are needed to ensure that hard work is met with success.

Here a very subtle theme in his book emerges – that these circumstances take a considerable time to arise and it make take even centuries. He is not afraid to take anthropological and sociological research findings on a variety of cultural issues and condense them into simple and persuasive arguments. As an example, Gladwell looks at the results of children across the world on maths tests and notes that there are parts of Asia where the children emerge a clear standard deviation ahead of children in other parts of the world. I was reminded of the book Spark (reviewed here) which looked at how children in one school in America who utilised a sophisticated exercise program were able to buck the national trend (although there have been other interpretations of this also). He relates this to cultures in which persistent hard work are encouraged and that this has been encouraged over centuries. He brings counterexamples to support his argument. He also brings his own story into the work. I thought that writing in this way was quite courageous as it can be very difficult to write publicly about such personal material. He outlines how the conditions experienced by his Jamaican ancestry were needed to culminate in the experiences he needed to arrive at where he is. Gladwell takes the issue of environmental influence on behaviour and gives it a new lease of life, communicating the ideas convincingly and at the same time espousing the influence of cultural legacy and hard work as well as also raising the possibility that we can as a society move towards an environment which affords the needed (good enough) opportunities for all.

References

Malcolm Gladwell. Outliers. Read by Malcolm Gladwell. 2008. Hachette Audio

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The article reviewed here is a review article – ‘The Accuracy of Prevalence Rates of Multiple Sclerosis:A Critical Review’ by Poser and Brinar. There may be psychiatric comorbidity with Multiple Sclerosis including depression and cognitive dysfunction. Epidemiology plays an important role in the management of illnesses identifying trends, clarifying associations and establishing the illness burden at a population level which can be used in resource allocation. In this paper, the authors set out to critically review the literature on prevalence rates in Multiple Sclerosis (MS). One of the authors was involved in the establishment of one set of diagnostic criteria. In the introduction, the authors write that

‘Hundreds of epidemiologic studies measuring MS prevalence rates (PR) have been published all over the world‘

The authors state that is their intention to demonstrate uncertainties over the established prevalence rate of Multiple Sclerosis. There is no stated methodology for the review and it is possible that by setting out to demonstrate this point that there is a risk of selection bias in the cited studies. Indeed for this reason, a meta-analysis with clearly stated inclusion and exclusion criterion for papers could be justified when attempting to answer questions about the prevalence rates. A number of review articles do not necessarily follow a systematic approach and instead focus on established experts in the field identifying relevant papers and trends. In this paper, the authors argue that there are a number of factors which confound the establishment of prevalence rates for Multiple Sclerosis. The confounders are illnesses which share features with Multiple Sclerosis. Thus a significant proportion of the review is concerned with the distinction between Multiple Sclerosis and Disseminated Encephalomyelitis (DEM)  (including the recurrent form). This discussion is quite involved and includes evidence from neuroimaging as well as a comparison of the clinical course of both illnesses. The authors argue that in a number of studies, DEM has been included under the label of MS.  The authors also consider the overlap with Neuromyelitis Optica and MS as well as the occurrence of silent MS.

The paper shows some of the considerations that are taken when establishing prevalence rates. They would also be relevant to diagnostic construction. The questions here could be further tested using a meta-analysis.

References

Charles Poser and Vesna  Brinar. The Accuracy of Prevalence Rates of Multiple Sclerosis:A Critical Review’. Neuroepidemiology. 2007. 29. 150-155.

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

The featured paper is ‘Cognition in Multiple Sclerosis: A Review of Neuropsychological and fMRI Research’ by Genova and colleagues. As the title suggests the authors examine the characteristics of cognition in Multiple Sclerosis. I could not identify a stated methodology. However the authors cite 140 papers throughout the paper which is reflected in both the breadth and depth of  relevant material covered. Broadly speaking the paper is divided into a section on neuropsychological profiles and another on the findings in functional MRI studies. In terms of neuropsychological profiling, the authors cover constructs ranging from working memory through to fatigue. They focus on the relationship of processing speed to a number of other constructs and suggest that clarifying this relationship further would be an important aim for future research as it would have implications for therapeutic strategies. Essentially if processing speed impacts on working memory and complex task completion then research in this area would be expected to inform therapeutic strategies. On the other hand, if there are confounders then they suggest that this would necessitate multiple treatment approaches. The authors explain a number of concepts as they cover material and I found this quite helpful. I find that this approach works really well in review articles and more so in those that cover many domains. With regards to fMRI studies, the authors emphasise the neuropsychology. Again their arguments are easier to follow as the article is to some extent self-contained allowing referencing to previously explained concepts. The authors draw attention to some of the conflicting findings in the field and the reader is able to use this information to facilitate selection and interpretation of future studies in this area.

The authors have written a clear exposition of the subject, carefully explaining important concepts and leaving the impression that the subject has been comprehensively covered in the neuropsychological domain. The relevance of processing speed to cognitive dysfunction looks to be one of the big questions in this field at the moment.

References

Genova H M, Sumowksi J F, Chiaravalloti N, Voelbel G T and DeLuca J. Cognition in multiple sclerosis: a review of neuropsychological and fMRI research.

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[archives]

The article reviewed here is itself a review article ‘Frontal-Subcortical Dementias’ by Raphael Bonelli and Jeffrey L Cummings. Cummings is a prominent figure in the field of Subcortical Dementia and has edited a book on the subject. This article is what I would term an expert review. Although there is no stated methodology there is a carefully considered overview of the field with the authors demonstrating a deep understanding of the field. They argue for the existence of a frontal-subcortical dementia. Thus they group an extensive list of conditions under this heading for the purpose of identifying common clinical features. While the section on anatomical circuits of frontal-subcortical dementia is useful, I found the discussion of neuropsychological features in the frontal-subcortical dementias to be particularly interesting. One of the tables in the paper covers ‘contrasting characteristics of cortical and frontal-subcortical dementia syndromes’ and distills a lot of material into an easily understandable format. The two types of dementia are contrasted in domains such as memory, visuospatial skills, calculation and mood. Even the simple presentation of the material in this way offers the reader a new perspective on a heterogenous conditions which they demonstrate have just as many shared properties as they do differences. The concept of a frontal-subcortical dementia may become more influential and it will be interesting to see how this develops.

References

Raphael Bonelli and Jeffrey L Cummings. Frontal-Subcortical Dementias. Review Article. The Neurologist. Vol 14. Number 2. 2008. 100-107.

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Research on Antidepressants

The British Journal of Psychiatry features two interesting studies on antidepressants. The first features 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.

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.

Blog Round-Up

Just to mention that the dead salmon study is generating a buzz in the blogosphere. The question is why the salmon’s brain activity showed up on the fMRI scan. Three issues affecting the interpretation of fMRI data are described in Developing Intelligence’s article – multiple comparisons, cluster comparisons and independence of multiple tests. For the interested reader, the pdf of the poster is located here. The authors presented the salmon with photographs followed by a ‘rest’ period and then analysed the change in BOLD signals in voxels. They performed one analysis without corrections. This ‘revealed’ a region of activity in the Salmon’s brain. They then carried out two types of comparison that are routinely used in the analysis of fMRI data using software packages such as SPM2. These corrections are necessary because if there is ‘random noise’ then some voxels should be firing above the threshold level just by chance. Thus you need to correct for both the combination of chance and the large number of voxels that are being examined. The two methods that are routinely used and included as a default in one statistical package are family wise error rate correction and false discovery rate correction.The debate that is currently taking place revolves around some posts which have likened these results to those of another study originally called ‘Voodoo Correlations in Social Neuroscience’ (reviewed here) and provoking much scandal before it surreptitiously changed its name to ‘Puzzling High Correlations in fMRI Studies of Emotion, Personality and Social Cognition’ (reviewed here). The point made in the Developing Intelligence article is that the ‘Voodoo Correlations in Social Neuroscience’ paper focused on independent tests whereas this paper focuses on multiple comparisons and thus a number of bloggers have misrepresented the paper. I would argue that both sides are probably right. Thus (and at the risk of sounding slightly pedantic), the Voodoo/Puzzling paper takes a broad swipe at fMRI study methodology from the statistical analysis right the way through to the way in which the analysis is presented within the papers. Thus

1. They do explicitly at one point, mention within-subject comparisons (i.e. changes occuring between tasks in the same subject)

2. In the second part of the discussion, the authors specifically ask the rhetorical question

‘Is the problem being discussed here anything different than the well known problem of multiple comparisons raising the probability of false alarms?’

In their response, the authors state that ‘The problem we describe arises when authors then report secondary statistics on the data in the voxels that were selected originally‘ before then adding ‘In the case discussed in this article, correlations are both the selection criterion and the secondary statistic‘.

3. However, most telling is Vul et al’s response to the responses to their original paper (available here) where they state explicitly that

‘6. We pointed out that although most studies used appropriate multiple comparison corrections (and thus identified voxels that do indeed have nonzero correlations), these methods are not always correctly applied, even in articles that have passed peer review’

One salmon tries to leap over a large waterfall while the other jumps into a hungry bear's mouth

However, taking the study a little further in a slightly tongue-in-cheek fashion, one interesting question to ask is

‘Why was any activity being picked up at all?’

The fMRI scan typically picks up oxygenated-Haemoglobin and it is the change in oxygentation of the Haemoglobin with delivery to the brain tissue that produces the signal. So if the Salmon was dead, we could safely assume that there was neither blood flow nor any delivery of oxygen to the brain tissue. So where is the change coming from? Well, I thought there was something fishy going on here and I was unsurprised to find a paper on the analysis of Salmon blood (freely available here). After looking very briefly at this paper, it appears the researchers in the fMRI study have omitted some crucial details for the interpretation of the data. Thus we do not know if their selected Atlantic Salmon was caught in fresh water or bracken water, as the corresponding temperatures would affect the oxygen dissociation curves of the salmon’s haemoglobin. We also need further information on the temperature of the room at the time of the scanning as well as the period of time for which the salmon had been deceased.

There is one possible explanation for the BOLD signals. They could represent a dissociation of the oxygen from the Haemoglobin with time. When the dissociation occurs, the magnetic properties of the Haemoglobin are altered and this will be picked up by the MRI scanner (oxygenated Haemoglobin is diamagnetic and deoxygenated Haemoglobin is paramagnetic). On moving from the presentation of the photographs through to the rest period there may be a continuing dissociation of oxygen from the Haemoglobin and it is this which is being picked up by the scanner. More interesting (and a very remote possibility) is that the authors of the poster have picked up deoxgenation in the Salmon’s Substantia Nigra, a region which is associated with Parkinson’s Disease in humans. The reason I mention this region is two-fold. Firstly, on the admittedly low resolution image of the Salmon’s brain on the poster, in the sagittal section, the activity is located close to the spinal cord and may therefore correspond to the midbrain (although I know next to nothing about Salmon neuroanatomy. I did however find a reference to the Substantia Nigra in Salmon). Secondly, in humans at least, the Substantia Nigra contains Haemoglobin which may offer it some protection during periods of anoxia and which also gives it the has a characteristic dark stained appearance (hence the name Substantia Nigra*). Salmon do a lot of moving about (as in the above picture) and the Substantia Nigra is involved in the regulation of movement. However against this hypothesis, the corrections in the statistical analysis eliminated the activation patterns, and there were at least two areas of activation in the uncorrected analysis.

Human Substantia Nigra - From Gray's Anatomy 20th Edition

So in summary, there’s a remote possibility that the imaging study was picking up the dissociation of oxygen from Haemoglobin in the Salmon’s Substantia Nigra post-mortem or as they infer, the activity was due to their incomplete analysis (particularly as the differences disappeared after the necessary corrections were made).

* The characteristic dark appearance of the substantia nigra is from the melanin in dopaminergic neurons.

Addendum

There may be another explanation for the findings. Thus if there is a mix of red blood cells (RBC) of varying levels of oxgenation, then the scanner may causes a realignment of the RBC’s according to their magnetic properties. If the magnetic field is applied as a pulse, then there will be further realignments when the magnetic field is changing. This may produce eddy currents, in which the Haemoglobin generates a reactionary magnetic field which will then ‘resist’ the next pulse of the scanner. If this were the case, it means that Haemoglobin molecules would undergo a more marked change in alignment during the initial part of the scan and this might explain the difference.

On a slightly different note, the brightest light in the known universe – the Diamond Light Synchrotron (see Podcast review here) is being used to examine iron deposits in Alzheimer’s Disease and together with the finding of Haemoglobin in the Substantia Nigra A9 cells, this is a very current area of research.

Addendum (4.10.9)

See the comment below from the author of the poster – Craig Bennett (also author of the blog at prefrontal.org) on the interpretation of the results.

References

Price J et al. Emotional side-effects of selective serotonin reuptake inhibitors: qualitative study. The British Journal of Psychiatry. 2009. Vol 195. No 3. 211-217.

Uher R et al. Adverse reactions to antidepressants. The British Journal of Psychiatry. 2009. Vol 195. No 3. 202-210.

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

The podcast reviewed here is Nature Neuropod – August 2009 edition featuring Kerri Smith. The sounds quality is very good as would be expected from a Nature production. I couldn’t hear any background noise (e.g. clicks) and the dialogue is very clear and features interviews with neuroscientists. The podcast can are also displayed in segments, so that you can play individual parts of interest rather than listening to the entire podcast.

The August edition features an interview with a members of a team that is constructing a multimodal map of the brain. They have significant ambitions to replace Brodman’s map with something far more sophisticated and which will superimpose neurotransmitter data and fMRI to produce what they describe as a ‘Google Map’ and presumably means that information on different brain regions will be easier to locate. Mind Hacks also covers the podcast here. An intriguing post looks at ‘jumping genes’ or transposons/retrotransposons in the hippocampus. The transposons are genes that move about within the genome and are thought to be drivers of evolution. For instance in this Science Daily article there is a report on research into grapevine transposons and a comment on how they might have impact on genetic diversity.

In the Neuropodcast there is also a look  at a study of synaptic formation in the retina. In the study, the researchers challenge the notion that competition is required for shaping synapses between bipolar cells in the retina and offer a potentially new paradigm for synaptic formation.

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The blog reviewed here is ‘The New Social Workers Blog‘  which is a companion to a free American online quarterly magazine ‘The New Social Worker‘ a magazine written for social worker students and recent graduates. 

In terms of the presentation, the title pane is a white on blue background. The general background is a light green colour while the posts contain black text on a white background. At the bottom of the main pane, there is a Blog Archive which indexes articles according to the month they were posted. At the time of writing there are two right-hand panes. The first has a green background and contains links to sites related to the blog and magazine. The second, lower pane has a white background and links to the twitter account for the New Social Workers, as well as containing links to the blog authors, followers, a blog-roll and the RSS feed. The blog archive dates back to 2008.

The first post is written by Ms T.J who has written almost all the blog articles and here explains that she is doing a full-time Masters in social work. Ms T.J writes about her experiences both on the social work course and in her own life. We hear about the sad deaths of a number of her close friends, the completion of course work assignments, Ms T.J’s other role as a writer for a magazine amongst many other postings. 

Here are just a few of the posts (and links) I liked

A post about National Social Work Month. This got me thinking. Maybe there’s a place for a National Psychiatry Day!

A post about the use of technology in social work with some comments about how web technology is already making an impact.

How the Homeless stay connected online. A post about a homeless man who runs an online forum as well as maintaining a significant online presence while sleeping under a bridge!

A link to this article on some ways in which technology is impacting on social work.

The ‘New Social Workers Blog’ gives the reader an insight into the experiences of  an American social work student and it will be interesting to see how the blog progresses with the course that Ms T.J is undertaking. 

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The audiobook reviewed here is ‘One Nation Under Therapy (Unabridged)’ by Christina Hoff Sommers and Sally Satel and narrated by Dianna Dorman. Dorman narrates clearly and with expression. I found that the narration made the material easy to listen to and helped to keep my attention focused.

As I wasn’t familiar with the authors before listening to this book I performed a quick Google search. Christina Hoff Sommers has been a Professor of Philosophy and has a Wikipedia article (a.k.a internet biography) which covers some of her other works as well as her views on gender and equity feminism. These views have apparently provoked much discussion. Dr Sally Sattell is a psychiatrist who is also widely published and amongst her other works is a look at political correctness in medicine. Sattell also has a Wikipedia article.

I found the content very interesting. Some of the material might be considered controversial but it can be argued that such dialogue is necessary as it facilitates reflection on and appraisal of practice. The authors focus on a number of issues relating to therapeutic intervention. One of the themes they explore is that of vulnerability of children. Thus they argue that children in schools are being increasingly ‘cushioned’, for instance being given less homework or parents responding to PE lessons that are considered too difficult. The authors are referring to the American schooling system in their work although it can be argued that it can be difficult to generalise as there will be heterogeneity not only between schools but also between pupils within the same school.

They also discuss how bereavement theories developed by Colin Murray Parkes, John Bowlby and Elizabeth Kubler-Ross (‘On Death and Dying‘) have been misinterpreted and also refer to Freud’s Mourning and Melancholia. Thus they argue that following bereavement, the bereaved will not necessarily follow a strict phases but that there will be considerable variation between individuals and that abnormal’ bereavement necessitating treatment occurs in a relatively small percentage of the bereaved (see also this review on Art Therapy and Bereavement). They also comment on what they describe as a movement towards providing counselling in those that have been recently bereaved despite the above although again this may be too fluid and heterogenous to characterise.

During the discussion of Post-Traumatic Stress Disorder there are many references to British Psychiatry including Professor Simon Wessely and an interesting quote from Aubrey Lewis who noted that the number of new cases of neurosis did not seem to increase during the Blitz in Britain. They consider the origins of PTSD in detail and look at some of the issues in the empirical research. They consider situations in which treatment for traumatic experiences is not warranted.

The term they use through the book is that of therapism, which is a movement they trace to therapists such as Carl Rodgers. They consider historical aspects of the origins of the person-centred movement that filled the gap created by the decline in the popularity of psychoanalytic psychotherapy. They argue that some of the values found within this movement have permeated society through various educational programs and that this perspective can create difficulties in establishing moral responsibility.

The authors raise many issues in an uncompromising and engaging style and this is a work which may continue to provoke much needed discussion.

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The article reviewed here is ‘Exploring the Persistence of Paper with the Electronic Health Record’ by Saleem and colleagues. The advent of the computer brought with it the promise of a revolution in the way that we work and visions of endless tasks that could be automated and data that could be stored out of sight and called up at any time from multiple locations. Much of that vision has been realised but paper based systems still persist even when electronic alternatives are available. This applies to health services as well as other sectors. The researchers in this study wanted to find out why health care workers continued to use paper based systems when electronic alternatives were available. They used a qualitative approach and in the paper’s abstract they conclude that 

‘In several cases, paper served as an important tool and assisted healthcare employees in their work. In other cases, paper use circumvented the intended EHR design, introduced potential gaps in documentation, and generated possible paths to medical error‘

The authors have therefore found both advantages and disadvantages to the use of paper from their study although their conclusions include the qualifiers ‘potential’ and ‘possible’. Furthermore, these results represent the healthcare worker’s opinions and experience of working within the system and therefore tell us about the system itself indirectly. Ideally this information could have been used to generate simple hypotheses which could have been tested using data from the system itself. Even so, it’s interesting to hear from the people using the system as their views may be translatable to similar services elsewhere.

What was the methodology?

The researchers conducted 20 semi-structured interviews with ‘key informants’ consisting of multidisciplinary professionals including doctors, nurses, pharmacists, IT and administrative staff. They provided an interview script in the Appendix. The term CPRS given in the example questions refers to the computerised records system. The questions were grouped into those for clinical staff and those for IT personnel. An example of a question for the clinical staff is 

‘What is your ideal workflow during your clinical work and how does it relate to CPRS?‘

An example of a question for the IT and administrative staff is 

‘Are there workflow improvements that you envision that could eliminate or reduce production and storage of some paper forms? Please explain‘

The questions were exploratory. This meant that the researcher could respond with further unscripted questioning depending on the subjects answers. 

What were the results?

The results were grouped into themes. They were difficult to summarise given the heterogenous responses elicited but some of my highlights are given below

1. Efficiency. Doctors would prefer to handwrite complex orders as this was thought more difficult using the system.

2. ‘Knowledge/skill/ease of use’. In some cases clinicians were simply uncomfortable using the system and in other cases were unaware that tasks could be completed within the system.

3. Memory. This was interesting. Some clinicians used paper to help them remember things.

4. Sensorimotor preferences. Subjects would sometimes like to hold the paper as it was ‘tangible’ and a physician expressed the view that it would impair communication with the patient if used during the interview (although from the comment, I think this rests on the assumption that the clinician would have to face away from the patient while using the computer).

5. Awareness. In some cases, staff would ask the patient to hand their blood pressure measurements in paper form to the physician

6. Task specificity. Sometimes the system would present the physician with information relevant instead to their colleagues. One physician therefore ensured that only alerts relevant to him/her were printed out and stored.

7. Task complexity. At times the system could not manage certain complex tasks at all and a paper workaround was necessary.

8. Data organisation. Clinicians sometimes needed to view the data in different formats that were unsupported and moved instead to paper.

9. ‘Longitudinal data processes’. The researchers cite the example of viewing longitudinal INR values which was not possible on the computer system.

10. Trust. Paper was viewed by one clinician (secondary source) as providing ‘proof’ that they had documented an item.

11. Security. Due to use of a university e-mail account, paper print-outs were used in one case to avoid use of the e-mail.

Conclusions

The authors discuss the results above and draw a number of conclusions including the following:-

‘Paper-based processes are not always inefficient or inferior to corresponding computer processes. However, paper processes may circumvent the intended use of the computer system, increase the opportunity for losing clinical information, and create new potnetial paths to medical error‘

However, there are a number of limitations to this study. Firstly, the researchers did not conduct further tests to verify the results objectively. For instance, they could have observed subjects engaged in tasks and quantified their work patterns as further supporting evidence. Thus these results serve to inform further studies. Secondly, there is a small sample set consisting of professionals from a number of different disciplines. Doctors form a small sample of this group. Thus to gain more useful information specific to a profession such as doctors, further studies would be required. Thirdly, the study relates to a very specific computer system at a specific point in time and therefore a number of the results may become redundant as the system is further refined through time. 

In conclusion, the study provides preliminary evidence that paper has many useful properties which have not been translated into one example of a computerised patient record system. Perhaps this is unsurprising, given the amount of time which paper has been used in civilisation.

References

Saleem J J et al. Exploring the Persistence of Paper with the Electronic Health Record. International Journal of Medical Informatics. 78. 618-628. 2009

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

The paper reviewed here is ‘Development of Criteria for a Diagnosis: Lessons from the Night Eating Syndrome’ by Stunkard and colleagues. The authors of this paper argue for the inclusion of a syndrome ‘Night Eating Syndrome’ (NES) in DMS-V. DSM-V, although not yet published,  has already produced a lot of interest. Many groups recognise this as an important time to influence the classification of mental illnesses. In their abstract, the authors conclude by writing that

‘..research on NES supports the validity of the diagnosis and its inclusion in DSM-V‘

So the question to ask on reviewing this paper is ‘Do the authors justify their conclusions?’.

The authors begin by quoting Blashfield et al’s 5 criteria for inclusion in DSM-IV. As I wasn’t familiar with Blashfield’s work I performed a quick internet search and found that he is a Professor of Psychology who has a particular interest in diagnostic classification. He was part of the working group for Personality Disorders in DSM-IV. He’s written a number of papers on diagnostic classification and has developed evident expertise in this area. Blashfield’s criteria are 1. ‘There should be at least 50 journal articles on the proposed diagnostic category in the last 10 years….’ 2. Diagnostic criteria should ‘include self-report measures, structured interviews and rating scales’ 3. ‘There should be at least 2 empirical studies by independent research groups demonstrating high interclinician correlations’ 4. ‘The proposed category represents a syndrome of frequently cooccurring symptoms, described in at least 2 independent studies’ 5. ‘There should be at least 2 independent empirical studies showing that the proposed category ” can be differentiated from other categories with which it is likely to be confused’.

Before looking at how the authors have addressed each of these 5 criteria, how useful are these criteria? Turning to the first point – ‘there should be at least 50 journal articles’ -  this seems like an arbitrary number. Why not 100 or 25? Does it matter which journals the articles appear in? What kind of articles should they be? Do editorials count? or reviews? or letters? The qualifier that they should be ‘in the last 10 years‘ also raises other issues. This qualifier means there should be, on average, 5 papers a year for those 10 years. Practically speaking there are going to be certain people or groups that are interested in specific syndromes. If this is so, then it would mean that they would need to have a high and consistent output for at least 10 years in the area of the syndrome. If they wanted the syndrome of interest to make it into DSM they would need to adopt a long-term perspective with sustained investment of (probably) significant resources.  This means that there would be a 10-year delay before new diagnoses make it into DSM and if you add the time between publication of DSM editions this could be up to 15 years. This means that people may not have commonly agreed diagnostic criteria for well over a decade and may use alternative diagnostic criteria. Within the dementias for instance, Lewy Body Dementia is one diagnosis that has more recently emerged and would benefit from the support of diagnostic classificatory systems such as ICD and DSM.

Turning to point 2, this seems entirely reasonable. The aim here presumably is to triangulate the evidence base for the diagnosis and it could be argued that this should be taken even further. Point 3 raises similar issues to point 1. Why the choice of 2 empirical studies? Surely there is a more subtle use of the empirical data which could be used in place of this. Although they refer to interclinician correlations perhaps a reference to construct and face validity might be more useful or instead of 2 empirical studies – a threshold value for inter-rater reliability. Point 4 also makes reference to 2 studies while also referring to ‘frequently cooccurring symptoms’ which is a defining feature of a syndrome – a symptom cluster. Finally Point 5 refers to the differentiation from other categories. It can be argued that this is a very useful feature as ideally it would mean that syndromes included in DSM should have little diagnostic overlap. However, many illnesses do have an overlap and the distinguishing features may take a while to emerge offering another perspective on cross-sectional empirical studies which demonstrate good diagnostic separation.

Even though these shortcomings can be raised, there has to be a starting point. The authors proceed to work through each of the criteria showing how the data has been accumulated to satisfy most of the points. The diagnostic criteria are described thus

‘1. evening hyperphagia (the consumption of at least 25% of daily food intake after the evening meal)

2. three or more nocturnal awakenings with ingestions per week, or

3. both behaviors (1 and 2)’

On the third point however they recognise a need for multicentre trials with independent investigators demonstrating good inter-rater reliability. They then add some supporting features for the diagnosis. They argue that it may act as a ‘pathway to obesity’ and that there is ‘psychiatric comorbidity’. In this regards I was intrigued to see an associated with ‘depressed mood’ but the authors note that

‘many night eaters become more depressed in the evening‘

I presumed that they italicised the word ‘more’ in order to distinguish it from the low mood that is characteristically described in the morning in depression. If this is the case, then it should be noted that the diurnal mood variation described in depression is characteristically described in the mornings but can occur in the evenings also – the important feature is that there is a consistent change in mood. So the next question to ask is ‘Can night eating form part of the clinical picture of depression?’. If it can then that has implications both for depression and for the night eating syndrome. There are further arguments in support of the diagnosis including features of the circadian rhythm.

I would be more convinced if there were substantial arguments to distinguish this syndrome from ‘healthy behaviour’. ‘Healthy’ might not be the right word here but what I mean by this is why does someone getting up at least 3 times a week and eating constitute an illness behaviour? I think it is reasonable at this stage of an illness construction to provide arguments to distinguish this ’syndrome’ from healthy thoughts, feelings and behaviours. People might for instance wake through the night for other reasons and the eating becomes associated with this period of wakefulness.

The ‘midnight snack’ in the UK became a cultural icon occurring in clever marketing campaigns for certain drinks, foods.

The R Whites campaign even won an international award for their campaign in the early 70’s. The authors also show that the SSRI’s can be useful in managing this syndrome and this emphasises the importance of distinguishing this from healthy behaviours.

While the authors provide lots of supporting evidence, it is precisely at this stage that the diagnosis needs to be examined critically and wider dialogue engaged in.

References

Stunkard A J et al. Development of Criteria for a Diagnosis: Lessons from the Night Eating Syndrome. Comprehensive Psychiatry. 50. 2009. 391-399.

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The article reviewed here is ‘Distinct MRI atrophy patterns in autopsy-proven Alzheimer’s Disease and Frontotemporal Lobar Degeneration’ and is freely available here. In the abstract, the conclusion reads

‘Compared with FTLD, AD patients had decreased gray matter in posterior parietal and occipital cortex, whereas FTLD patients had selective atrophy in anterior cingulate, frontal insula, subcallosal gyrus, and striatum (p<.001, uncorrected). These findings suggest that AD and FTLD are anatomically distinct, with degeneration of a posterior parietal network in AD and degeneration of a paralimbic fronto-insular-striatal network in FTLD‘

There were a lot of findings in this study which obviously generated a lot of data. However the conclusions above focus on answering a specific question from the data set – is there an anatomical difference between the brain atrophy that is seen in Alzheimer’s Disease (AD) and that seen in Frontotemporal Lobar Degeneration (or FTLD for short)? The researchers are quite clear in their conclusions. In AD there is degeneration in a posterior parietal network and in FTLD there is degeneration in a fronto-insular-striatal network. The temporal lobes are presumably being omitted from the conclusions because the temporal lobes are affected in both conditions.

In terms of selection of subjects, the researchers have excluded Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP) due to the pattern of anatomical involvement (see (Sha et al, 2006) for a discussion both for and against the amalgamation of FTLD, PSP and Corticobasal degeneration). This exclusion would be expected to reduce the parietal involvement in the FTLD group however as the researchers note that CBD has  an asymmetrical parietal lobe involvement. The researchers then sample a subgroup of subjects that had undergone postmortem at the University of California San Francisco Memory and Aging Centre with confirmed diagnosis of AD or FTLD. I wasn’t entirely clear on how the sampling was done (e.g. was it consecutive post-mortems?) and so there may be another source of selection bias. A number of subjects were excluded for a variety of reasons including movement artefact during the antemortem MRI studies. Antemortem dementia severity was assessed using the Clinical Dementia Rating Scale. Diagnosis was obtained antemortem using the NINCDS-ADRDA criteria for AD which I understand are quite robust and the Neary consensus criteria for ‘FTD clinical syndromes’ (other criteria for FTD have been developed subsequently).

A 1.5 Tesla MRI scanner was used and the earliest scans for subjects were included in the analysis. The authors used a previously described protocol for the Voxel Based Morphometry. Multiple comparisons were made of the voxels – AD with FTLD, AD with controls, FTLD with controls and so on. The researchers corrected for multiple comparisons by using family-wise error correction and the analysis was undertaken using SPM2. A protocol was also used for the post-mortems and the researchers specify NIA-Reagan criteria for AD and McKhann work group diagnostic algorithm for FTLD. SPSS was used for the statistical analysis and ANOVA, t-tests or Chi-squared tests were used depending on the data type.

The results of the VBM are displayed very succinctly. Comparison of AD and FTLD were shown very clearly. Both AD and FTLD had regions where the grey matter volume was on average greater than in the other group.  However I was surprised to see what was written about the correction for multiple comparisons. After the correction for multiple comparisons the only significant finding was that the grey matter volume in the striatum was larger in AD than in FTLD.

So does this negate the conclusions drawn in the abstract quoted above? It seemed so to me. I double checked the results and then looked at the discussion. In the discussion, the researchers actually comment on the correction for multiple comparisons. They write that the uncorrected anatomical differences between AD and FTLD fitted with their a priori hypotheses. These same conclusions though surely go against the assumptions in the methodology. If the correction for multiple comparisons is unimportant, why include them?

I wasn’t convinced and came away thinking that the main finding was that striatal degeneration may distinguish AD and FTLD. There are clauses though, even with this conclusion. Ultimately there was a small sample size. The confidence interval would have been wide for the volume differences which may have explained the lack of significance after multiple comparisons. The researchers give nice explanations for their hypothesised differences between AD and FTLD and it may well turn out that they are right but I don’t think this is the study to show that. Maybe this data can be aggregated with other data in a later meta-analysis (a case for an open-source imaging database for dementia studies (as in the Alzheimer’s Disease Neuroimaging Initiative).

References

Sha S, Hou C, Viskontas IV, Miller BL. Nat Clin Pract Neurol. 2006 Dec;2(12):658-65. Are frontotemporal lobar degeneration, progressive supranuclear palsy and corticobasal degeneration distinct diseases?

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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. 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.

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