Author: Dr Justin Marley

The paper reviewed here is a Norwegian study ”Selection Effects in Psychiatric Epidemiology’ by Nygard and colleagues. In the abstract, the authors conclude that

‘Studies of predictors ought to have a long follow-up, as several years might pass before differences in mortality are revealed‘

In the introduction the researchers discuss some of the varied results from studies looking at the association between mental illnesses and mortality. Some have shown a reduction in mortality, others an increase and still others no difference with samples from the general population. The researchers used a longitudinal design here with an assessment instrument -the Hopkins Symptom Check List 25 – to compare a sample – the OsLof sample with a sample of the general population (from the Norwegian registry database).

Method

The researchers identified a random sample of 5000 people in Norway, over the age of 18. Letters were sent out and in 2726 ‘contact was obtained’. 712 declined to take part and 24 weren’t matched with controls (from a registry study from which 1% of the Norwegian population were sampled). Both samples were followed up between 1990 and 2003. The OsLof sample was stratified according to the Hopkins Symptom Check List 25 score – those above and below a threshold of 1.75.

Results

I won’t comment on all of the results here, just the two I found most interesting. Firstly they found that HSCL-25 scores were a predictor of mortality in the OsLof sample but this only became significant at 12 years (close to the study end) compared to the population mortality rates – 1.57 times higher mortality rates (I think this corresponded to the hazards ratio for men with a confidence interval of 1.26-1.97) . So essentially for 12/15 of the study years there was no significant difference.  The second result of interest was the in the first few years of the study, the OsLof sample had lower mortality rates than the registry sample, the implication being that those included in the OsLof were likely to be healthier supporting some of the other cited studies which examine the health of subjects that aren’t included in studies at the initial stages.

Conclusions

The authors conclude that relative to the healthy sample, those with a score on the HSCL of >= 1.75 showed a signifiacntly increased risk of mortality only after 15 years. They suggested that those who did not participate in the study may have had higher rates of metnal distress on the basis of other cited studies.

Returning to the issue of multiple copmparisons, i’m not sure if it applies here but I thought it could do. My reasoning is as follows. In the results section, the analysis the researchers have calculated the differences in mortality at several points in this longitudinal study. The more points at which this comparison takes place, the higher is the likelihood of a false positive necessitating a correction (e.g the Bonferroni correction). The other point here is the choice of the threshold of 1.75. There are obviously a large number of alternative thresholds that could be used. However I suspect this threshold was used because of  a previous study using this threshold for women and a threshold of 1.67 for men as optimum cut-off point (Sandanger et al, 1998).

The other point of interest here is to what degree a cross-sectional use of a symptom checklist should be used as predictor. The HSCL is being used as a proxy marker of anxiety and depression but there is an argument for a clinical diagnosis to support the results on the HSCL-25. The symptoms themselves may fluctuate over time. Additionally another study provides evidence that the scale should be validated in the specific cultures in which it is to be used (Ventevogel et al, 2007).

In summary, the study shows evidence of a selection effect for health in those included in the study relative to a sample from the population registry. It would be interesting to see the study replicated with a clinical diagnosis supported by quantitative measure of illness severity.  A difficulty in these types of epidemiological studies is that it is difficult to generalise to mental illnesses because this covers such a broad spectrum. The pending changes to the DSM-IV and ICD-10 will no doubt introduce a number of conditions not previously considered and so studies of this type could focus on specific illnesses as a proxy to the broader group of mental illnesses.

References

Nygard J, Klungsoyr O, Sandanger I and Svensson E. Selection Effects in Psychiatric Epidemiology. A 14-year prospective study of the Hopkins Symptom Checklist 25 as a predictor of mortality in the Norwegian general population. Soc Psychiat Epidemiol. 2009. 44. 881-886.

Sandanger I, Moum T, Ingebrigtsen G, Dalgard OS, Sørensen T, Bruusgaard D. Soc Psychiatry Psychiatr Epidemiol. 1998 Jul;33(7):345-54.Concordance between symptom screening and diagnostic procedure: the Hopkins Symptom Checklist-25 and the Composite International Diagnostic Interview I.

Ventevogel P, De Vries G, Scholte WF, Shinwari NR, Faiz H, Nassery R, van den Brink W, Olff M. Soc Psychiatry Psychiatr Epidemiol. 2007 Apr;42(4):328-35. Epub 2007 Feb 13. Properties of the Hopkins Symptom Checklist-25 (HSCL-25) and the Self-Reporting Questionnaire (SRQ-20) as screening instruments used in primary care in Afghanistan.

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The paper reviewed here is ‘Climatic Relationships with Specific Clinical Subtypes of Depression’ by Radua and colleagues. In their abstract the authors conclude that

‘The main findings were a negative 1-month delayed relationship between onset rates of episodes with melancholic features and a climatic factor mainly composed of ambient termperature/sunlight, and a negative 1-month delyaed relationship between onset rates of episodes with psychotic features and a climatic factor mainly composed of barometric pressure‘

In their introduction, the authors note the long history of a proposed association between climate and depression with holidays to specific locations suggested as a treatment as far back as the 19th century.

Methods

In the first part of the methodology section they describe their approach to gathering and analysing the climate data. They used climate data recorded between 1997 and 2004 and the data included

• Daily Mean Ambient Temperature
• Photoperiod
• Accumulated Solar Radiation
• Relative Humidity
• Rainfall
• Barometric Pressure

The clinical data was gathered from inpatients located within a specified distance of the metereological station. Patients included were over the age of 18 years, DSM criteria were used for single and recurrent episodes of major depressive disorder, as well as those with readmissions less than 2 months after a previous admission or where the date of onset of the episode was unclear. Interestingly there were no exclusion criteria for medical illnesses which I thought meant that the sample would be more representative of a clinical inpatient sample. The exclusion criteria above seem to be a sensible means of identifying a strong temporal association between the depressive episode and the climate data. Various types of demographica data were obtained.

The authors then discuss the analysis of the data. Part of the data involved the analysis of the climate data which I am not familiar with and so to a certain extent I wasn’t able to comment sensibly onthe methodological description or the results of this part of the data analysis. Thye used a Principal Components Analysis of climate variables with a particular transformation to produced what they refer to as an ‘Anderson-Rubin climatic factor’. They add in the methodology section that

‘Therefore climatic data were transformed from several highly correlated climatic variables to three uncorrelated climatic factors‘

So they transformed their data into a few factors that could then be correlated with the clinical data. They later state that

‘Relationships between the climatic factors yielded by the PCA and the onset rates of the different clinical subtypes of depressive episodes were tested by means of an Autoregressive Integrated Moving Average (ARIMA) procedure‘

There’s a brief explanation of the procedure here but I didn’t particularly understand the justifications for it from the description so again couldn’t comment sensibly on this aspect of the analysis. SPSS 15 is used for the modelling and Bonferroni corrections are made as multiple comparisons are made between the climatic factors and the subtypes of depression.

Results

The researchers identified 547 individuals with 770 hospitalisations. After exclusion criteria were applied there were 421 episodes. They found a few significant results. One of these was the relationship between ‘ambient temperature and sunlight’ and onset of unipolar depression with melancholic features with a 13 month delay. They argued that this 13 month delay would probably be due to an ‘artefact’ of a 1-month delay which just happened to fit better with the previous year’s data. When they repeated with a 1-month delay they found a significant relationship supporting their hypothesis. A significant correlation was also found between unipolar depression onset and barometric pressure with a 1 month delay in the former (p=0.003 after Bonferroni correction). They also found a significant correlation between onset of depression with psychotic features and barometric pressure with 2-month delay of the former.

Conclusions

The researchers discuss their results and some of the limitations of the study. I didn’t particularly understand all of the analysis particularly that of the climate data and the rationale behind the ARIMA procedure. Having said that the final results with p-values are easy to understand. This for me is one of the disadvantages of a cross-disciplinary study – that there is more ‘esoteric’ knowledge needed in order to fully understand the results. On the other hand, the potential rewards of such an approach are tremendous and in order to answer such a potentially clinically important question it seems hard to avoid collaboration with scientists from other disciplines. I would go back to what I said in a previous post namely that there should be an associated video file for the methodology which would take the reader/audience through the process of analysis in greater detail than is allowed in methodology section. I would argue that with such material available, hosted on a free service such as YouTube, the audience has a greater chance of fully understanding the analysis.

From this retrospective study, the researchers identify a relationship between barometric pressure, ambient temperature and sunlight and onset of various subtypes of depression as above. It will be interesting to see if this work is further replicated.

References

Radua J, Pertusa A and Cardoner N. Climate relationships with specific clinical subtyeps of depression. Psychiatry Research. 175. 217-220. 2010.

Index

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Disclaimer

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This image was created by Andrew Gillies and is licensed under the Creative Commons Attribution Share-Alike 3.0 License. See here for further details. GPe – External Globus Pallidus GPi Internal Globus Pallidus STN Subthalamic Nucleus SN Substantia Nigra

The article reviewed here is a brief letter titled ‘Catatonic Stupor in a Case of Pontine and Extrapontine Myelinolysis: Clinical and Radiological Dissociation’ by Miyares and colleagues and freely available here.  The authors describe a 23-year old man who presented with confusion, a stuporose state and that

‘During passive movements the limb was kept in the same position for a prolonged period even when the position and posture seemed uncomfortable and bizarre‘

This is a phenomenon also referred to as waxy flexibility. What’s interesting here is that the authors have identified neuropathology from the imaging investigations. Thus there were slow waves on the EEG and on the MRI they have identified T2 weighted hyperintense signals in two regions – the Pons and the Basal Ganglia (the Basal Ganglia are illustrated above in coronal section). Thus in conjunction with the clinical features they conclude that there is Pontine and Extrapontine Myelinolysis. He was treated with Risperidone and improved even though the hyperintense lesions remained.

I thought there were two interesting features here – the association with compulsive eating and the association with Pontine and Extrapontine Myelinolysis. In the draft version of DSM-V, consideration is being given to adding a catatonia specifier to the diagnosis of schizophrenia so that it’s presence or absence would be explicitly stated (see here). Catatonia can manifest in a number of different ways and there are most likely many different causes. In this case, the association of involvement of the Basal Ganglia with waxy flexibility is plausible but on the basis of a single case alone it is not possible to draw any firm conclusions.

A superficial examination of the literature using the Medline database (via PubMedNet) and using the keywords ‘Pontine Myelinolysis’ produces 777 results from 1959-2010 inclusive. A cursory inspection of the most recent abstracts reveals associations including a rapid correction of hyponatraemia (Mastrangelo et al, 2009)(Hawthorne et al, 2009), hypokalaemic nephrogenic diabetes insipidus (Davenport et al, 2010) and rapid correction of hyperammonaemia (Langer et al, 2010) amongst others (there were also cases associated with slowly corrected hyponatraemia, following liver transplantation, surgery for a craniopharnygioma as well as gestational diabetes). The association between a rapid correction of sodium levels and ‘osmotic demyelination’ or ‘pontine myelinolysis’ was emphasised by a number of the authors. Indeed the authors of this case study noted that the sodium levels as well as other urea and electrolytes were within normal limits on the current admission. However during an earlier admission they note that there was hyponatraemia and that this was corrected. Thus there is a possible explanation that encompasses the initial presentation with hyponatraemia through to the development of catatonia with waxy flexibility. It possible to speculate that compulsive eating may have influenced the rate of correction of hyponatraemia.

Is there A Relationship Between Pontine Myelinolysis and Neuroleptic Malignant Syndrome?

In an effort to triangulate these results with catatonia. I used the terms ‘catatonia’ and ’sodium’ for the same years and database but produced only 19 results which didn’t seem too interesting apart from the use of ‘dantrolene sodium’ for catatonia and also the consideration of ‘malignant catatonia’ better known as the Neuroleptic Malignant Syndrome. Could there be cases of Pontine Myelinolysis which result in NMS? Surprisingly the answer is yes. There were two papers identified by searching the same database/years using the terms ‘Pontine Myelinolysis’ and ‘Neuroleptic Malignant Syndrome’ produces one paper in english (Groff et al, 2005) and another in spanish (González et al, 2010). The spanish authors comment in the title on the similarity of the Pontine Myelinolysis presentation with that of NMS while the authors of the other paper note the development of pontine myelinolysis after NMS.

Conclusions

Case reports offer a useful starting point for asking useful clinical questions and starting a line of inquiry in response to those questions. If the DSM-V draft changes come to pass then catatonia will be considered more explicitly and may become a more prominent term in the literature meaning that case studies like this might become more frequent. Searches through medline produce potentially useful findings or associations. For instance one of the papers identified in the searches was about an 11-year old boy who had Pontine Tegmental lesions and who developed auditory and visual hallucinations (Vita et al, 2008). The authors of that study speculated that the lesions were interfering with REM sleep and that the hallucinations were in effect a phenomenon that should have been experienced in REM sleep rather than awake in the waking state  (the hallucinations involved Harry Potter). Interestingly there is another condition where REM sleep mechanisms have been invoked as causal explanations of hallucinations – Lewy Body Dementia which affects both subcortical and cortical regions.

In summary, pontine and extrapontine myelinolysis in this case was associated with catatonia. There is another case described above in which a pontine lesion was associated with visual and auditory hallucinations and may be a useful differential in psychosis. There were some experimental papers on treatment (including returning to the hyponatraemia state in an animal model and some suggestions by a Chinese group including the use of gamma globulins). As in the case report, treatment of Pontine/Extrapontine Myelinolysis would be managed by the neurologists and it is interesting to see how there is a potential for useful interdisciplinary discussion in areas such as this.

References

Davenport C, Liew A, Vic Lau P, Smith D, Thompson CJ, Kearns G, Agha A. Ann Clin Biochem. 2010 Jan;47(Pt 1):86-9. Epub 2009 Nov 25. Central pontine myelinolysis secondary to hypokalaemic nephrogenic diabetes insipidus.

González Robledo J, Ballesteros Herráez JC, Chamorro Fernández A, Martín Polo J. Med Intensiva. 2007 Aug-Sep;31(6):342-3. [Central pontine myelinolysis after malignant neuroleptic syndrome][Article in Spanish]

Groff KE, Lam C, Caroff SN. J Clin Psychopharmacol. 2005 Dec;25(6):620-1. Extrapontine myelinolysis resembling neuroleptic malignant syndrome.

Hawthorne KM, Compton CJ, Vaphiades MS, Roberson GH, Kline LB. J Neuroophthalmol. 2009 Dec;29(4):296-9. Ocular motor and imaging abnormalities of midbrain dysfunction in osmotic demyelination syndrome.

Langer JE, Wilson WG, Raghavan P, Rust RS, Goodkin HP. Pediatr Neurol. 2010 Feb;42(2):154-6. Extrapontine myelinolysis resulting in transient cortical blindness.

Mastrangelo S, Arlotta A, Cefalo MG, Maurizi P, Cianfoni A, Riccardi R. Neuropediatrics. 2009 Jun;40(3):144-7. Epub 2009 Dec 17. Central pontine and extrapontine myelinolysis in a pediatric patient following rapid correction of hypernatremia.

Vita MG, Batocchi AP, Dittoni S, Losurdo A, Cianfoni A, Stefanini MC, Vollono C, Della Marca G, Mariotti P. J Clin Sleep Med. 2008 Dec 15;4(6):588-90. Visual hallucinations and pontine demyelination in a child: possible REM dissociation?

Index

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Disclaimer

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

Dementia Reclassification?

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

Mental Disorders Due to a General Medical Condition

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

Personality Disorders

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

Substance-Related Disorders

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

Schizophrenia and Other Psychotic Disorders

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

Mood Disorders

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

Anxiety Disorders

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

Somatoform Disorders

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

Factitious Disorders

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

Dissociative Disorders

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

Sexual and Gender Identity Disorders

There are a number of new diagnoses.

Eating Disorders

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

Sleep Disorders

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

Childhood disorders

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

Impulse Control Disorders Not Elsewhere Classified

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

Adjustment Disorders

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

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

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

General

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

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

‘Addictions’

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

Anxiety Disorders and OCD

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

Intellectual Disability

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

Bipolar Disorder in Children

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

Autistic Spectrum Disorders

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

Eating Disorders

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

Index

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Disclaimer

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The podcasts reviewed here are the 15th and 16th episodes in Hoeven’s series of the Mind Podcast. In the 15th episode (available here) Hoevens looks at three aspects of perception. Firstly he considers the theme of constancy whereby sensory information is used to create constant perceptual features. He discusses a number of mechanisms which make this possible including monocular and binocular processes. For instance with monocular vision it is still possible to identify perceptual features by means of the movement of the object across the visual field for instance. He then discusses some of the processes used in binocular vision in the creation of perceptual features. Hoevens covers illusions briefly before moving onto the subject of learning and perception. Here he looks at a number of experiments which have provided evidence that aspects of perceptual processing can be both innate and learnt. While this is a brief introduction to the field, the listener can get a good feel for the subject from Hoeven’s treatment of the material.

The 16th episode is slightly longer than the average episode at just over 30 minutes (available here). Hoevens looks at consciousness and attention. There is a brief initial discussion of consciousness where Hoevens introduces the terms consciousness, preconsciousness, unconciousness and non-consciousness while also acknowledging the difficulties surrounding the definition of consciousness. Hoevens then looks at attention and describes some models of the processes that might be involved including early and late selection as well as the continuous model. He finishes with a description of some very interesting studies that have been undertaken which have been undertaken in people with an interruption of the interhemispheric connections. In the podcast these are referred to as ’split-brain’ studies but I wasn’t clear on whether these were callosotomies or developmental abnormalities or a mixture of the two that were being described. Nevertheless it was useful to be reminded of how studies in this area can inform our understanding of conscious and unconscious experiences.

Again Hoevens narrates in a relaxed style and uses a background of baroque music and even provides a musical interlude giving the audience space to consolidate their learning.

Twitter

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Podcast

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TAWOP Channel

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Responses

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Disclaimer

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 ‘Nou Stuff‘ by neuroscientist Maria Page. Page has an account on Twitter where she has already posted over 4700 tweets. These are mostly high quality links to articles on neuroscience and in this medium she is one to follow for those with an interest in neuroscience. Page also has this blog where she includes posts in which amongst other themes she has expanded on some of the material from Twitter.

Appearance and Design

The background and title pane feature a graded white-cyan space which evolves into angled and evenly-spaced lines with a plant motif.  There are several articles on each page. Each article features a white background with black text and a blue heading and comments are enabled. The blog can be navigated using features in the right hand pane. Thus the reader can use the search facility, the categories box and access top posts. There are also links to external sites as well as updates from the twitter account, delicious and the blog stats for the site. To move backwards chronologically the reader must click on the next page link at the bottom of each page sequentially.

Content

The first listed article was dated 20.7.09 and is a look which components of music are thought to convey emotion including the key and tempo. This is particularly interesting in view of emerging evidence of a close link between music and language. A neat feature of the articles is the inclusion of links to a series of relevant references providing the reader with additional and useful reading material. Page focuses in detail on some key areas. For instance in this post she looks at some of the possible neurobiological underpinnings of laughter. I found this material interesting in view of an evolutionary theory of laughter (see review here) although it should be noted that in our nearest relatives chimpanzees, smiling is seen as a threatening behaviour. Page also covers case studies of interest. For instance in this post, Page looks at patient H.M (who suffered a profound anterograde amnesia following a bilateral hippocampectomy for intractable epilepsy) and the post-mortem project to produce a virtual dissection. The posts contain a wide variety of material across neuroscience and are complemented by pictures or embedded videos.

Conclusions

This is a good neuroscience blog with articles varying from brief descriptions of new studies with links to detailed articles with useful references. This blog also complements the twitter posts by Page which provide the audience with current and interesting neuroscience posts. Gladwell has written about the number of hours it takes to develop expertise in an area and the evidence seems to point out that it is about 10,000 hours (see review here). Obviously the definition of expertise will vary from one subject to another but it will be interesting to follow Page’s combined blog and twitter postings. Assuming that an average of 5 twitter posts can be produced per hour (after scanning the articles) that would be roughly equivalent to 50,000 twitter posts (assuming all were about neuroscience). We are at the forefront of new social media technologies. What does a person become by posting 50,000 twitter posts about neuroscience? Obviously doing science is the core of being a scientist. Nevertheless the use of twitter involves finding material, reading and filtering material, communicating this and producing an index for this material for future reference. I would speculate that this process contributes meaningfully to the core abilities of a scientist not only in communicating and popularising science but also in receiving continuous feedback from peers. For instance with twitter, I’ve found it useful in quickly tapping into the ‘narrative’ of current events relating to psychiatry and allied disciplines. Thus I would say that the results of a using twitter are complex with many potential benefits. The use of blogging seems to complement this well. Will Page become one of the leading neuroscientists of the 21st century? Time will tell but the skills displayed here could be argued to be integral to the neuroscience team of the 21st century.

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The book reviewed here is ‘The Philosophy of Science’ by Samir Okasha and narrated by Peter Ganim. Ganim’s narration gives a strong impression of authority being low pitched with clear articulation.

In the first part of the book Okasha looks at Aristotle and his philosophy and its relation to science. He remarks on how some of the assumptions he made would look very unrealistic to us today. He moves onto discuss Karl Popper and his influential view of falsifiability. He notes Popper’s comparison of psychoanalytic theory with marxism and einstein’s theory of relativity. He notes that Popper was impressed with the kinds of predictions that Einstein was able to make. However he goes onto note that there have been theories which have been through some rough times and the proponents have stood by the theories and gone on to show the validity of such theories. Thus a lack of falsification of a theory isn’t necessarily a strength. Popper’s attacks on psychoanalytic theory are discussed. However Freud wrote many books and papers on psychoanalytic theory. He had some very clear ideas on the stages of development but he also identified other phenomenon such as the defence mechanisms as well as the nature of dream material. I would argue that just because the theory has a wide domain and wasn’t explicitly characterised for testability, the concepts contained therein are not invalidated. It is an easy approach to dismiss the theory but altogether more difficult to make a close study and aim towards a refinement. Indeed contemporary research in the area of psychoanalytic theory is doing just that. Perhaps philosophy is more useful in articulating those parts of the theory which should be tested or amended rather than testing their validity which is the role of science.

Okasha then introduces the listener to Hempel’s covering law simplifying it as an explanation of science where valid explanations can be predictions and vice verasa. However Okasha shows this to be incorect with an easily understandable example. He shows that such a law would in practice would be asymmetric rather than symmetric as predicted by Hempel. He goes onto address some of the general flaws in the argument and suggests that the law should be relevant to the phenomenon in question as well as the need for a causal chain. However even here he points out the difficulties with cause and effect invoking the arguments of David Hume a staunch empiricist. Okasha also discusses the debate between the realists and the antirealists. The antirealists believe that science can only draw conclusion about that which is observable. Okasha takes some time to detail the arguments and counterarguments. He seems to come down in favour of the realists or at least I found the arguments in favour of the realists more convincing. One particularly strong argument is that even if things are observable it doesnt mean that they are observed.

Okasha then looks at Kuhn’s ideas from ‘The Structure of Scientific Revolutions’ and details Kuhn’s suggestion that different theories are incommensurable. He also notes Kuhn’s suggestion that perception is altered by the assumptions in a theory. This Kuhn argues causes the scientists to perceive differently (presumably at a top level of perceptual processing). However Okasha challenges this notion by highlighting other arguments that have taken place in this area. Thus Einstein and Newton’s theories require only a partial translation. Okasha also tells the listener that Kuhn suggested that paradigm shifts occurred because there were particularly forceful proponents of a model who were instrumental in their popularisation. Kuhn was apparently criticised in that he was describing a ‘psychology of crowds’. Okasha explains that Kuhn was trying to address the assumptions of the remove the logical positivists who viewed science as rational, progressive and objective. He suggests that Kuhn wanted to use a more relaxied understanding of what a rational approach is. The relationship between science and philosophy is discussed later in the book and Oshama Okasha highlights the debate about the appropriateness of the methods of the natural sciences to social science. Oshama Okasha also discusses the debate between evolutionists and creationists. Sociobiological theories are examined in detail to illustrate the nature of this debate.

Having no training in philosophy, I found Okasha’s book provided a useful overview of some of the debates occurring in the philosophy of science and gives pointers to further reading on the basis of the philosophers discussed here.

References

Samir Okasha. The Philosophy of Science: A  Very Short Introduction (Unabridged). Audible Inc. Narrator Peter Ganim.

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The paper reviewed here is ‘The Operating Framework for the NHS in England 2010/2011′ and freely available here.

There is a foreword by David Nicholson, CBE. Here Nicholson describes the period 2010/2011 as a year of growth in the NHS and refers to a further document which outlines the plan for the next 5 years in the NHS. He emphasises a need for innovation, prevention, quality and productivity. Amongst other issues, he discusses the need for integration and ‘risk management across systems’. In reference to the latter he states that risk is a ‘zero sum game’ with risk remaining even when it is transferred within the system. In the context of risk management he also notes that all NHS organisations will need to be registered with the Care Quality Commission next year to assure specified standards are met. The intention to deliver more services closer to home at the end of the next 5 years is stated. The integration of both services and organisations in some instances is also discussed.

The next section places the operational framework in context. Thus the budget is discussed, the ‘need to generate …from existing resources’, the importance of focusing on preserving the workforce, the need for clinical leadership and the benefits of the national care service for social care delivery. Chapter 2 is about priorities. They identify three tiers within the NHS Vital Signs and also the National priorities. Of interest here is a section on health and wellbeing (particularly interesting in view of the article reviewed here) there is a reference to New Horizons and the emphasis on early identification of mental illness.  In this section, it is also stated that

‘All NHS organisations must play their full part in supporting health research….all providers of NHS care will want to continue to increase their level of participation and performance in hosting research funded by non-commercial and commercial research funders. As part of that, in their Quality Accounts we propose that NHS providers shoud include the number of patients recruited to clinical research‘

They also emphasise the role of Strategic Health Authorities with regards to clinical research and in engaging with ‘the work of the new NHS Life Sciences Delivery Board on the uptake of innovation in medicines and medical technologies’.

The third chapter deals with system levers and enablers. The financial framework is discussed here as is the Quality Framework. Indeed I found the diagram of the quality framework was quite helpful in gaining a rapid overview of the structure. There is also a description of the NHS Performance Framework where it is noted that

‘Mental health trusts: from April 2010 – to include a limited set of additional indicators on organisational governance‘

The final part of this chapter is on informatics where it is noted that

‘Ambitious and innovative approaches to digital technology should underpin the delivery of strategic business and service objectives…Digital technologies will connect all parts of the service together, by enabling access to health services through a wider range of communication channels‘

The last chapter is on planning and includes a discussion of issues such as ‘performance monitoring and assessment’, working in partnership with other organisations (e.g in crime reduction) as well as a timetable for action by Strategic Health Authorities. At various points in the document there are also references to the introduction of patient choice in the NHS constitution.

In conclusion, this 56 page document contains a lot of information which is of interest to various audiences and there is an emphasis in places on detailed financial outlines. There were a few references to mental health services as well as a validation of the importance of research in the NHS and a key role for informatics.

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The paper reviewed here is ‘Mental Illness and Well-Being: The Central Importance of Positive Psychology and Recovery Approaches’ by Mike Slade and freely available at the BMC Health Services Research site here.  In the abstract, Slade writes that

‘A new evidence base is emerging, which focuses on well-being. This makes it possible for health services to orientate around promoting well-being as well as treating illness, and so to make a reality of the long-standing rhetoric that health is more than the absence of illness….If health services are to give primacy to increasing well-being, rather than to treating illness, then health workers need new approaches to working with individuals‘

In the 54-page PDF article, Slade begins by discussing the concept of the deficit model of illness and by noting the partial dissociation of mental health and  mental illness implying that the two may require separate approaches. He then looks at recovery – a big topic. He outlines a number of taxonomies – service based recovery, service based user recovery, clinical and social recovery while emphasising the essence of recovery as a continuous and personal process. As a result of this he challenges the use of traditional methods used in management of illness including the care pathway (although I would argue that a more ‘dynamic’ type of pathway would make it possible).

Next he turns to positive psychology. Here he gives the reader a broad overview of the subject and writes about the dimensions that have been used in defining in well-being. He writes about the use of a framework for mental wellbeing which uses the concepts of flourishing, struggling, languishing and floundering and the prevalence of these different states of well-being in the population.  He also describes Seligman’s four types of good life and the subsequent importance of ‘flow’ in lifestyle and that

‘Feeling good is not always necessary for a good life‘

He also describes how goal-setting and goal-striving can be structured within services. What I was particularly intrigued by was the concept that mental illness and mental wellbeing could be addressed both independently and simultaneously.

Slade goes on to draw parallels between the recovery and positive psychology movements. From his description it sounds like a top-down versus bottom-up approach with the recovery movement also having more influence as a result of the approach used. He goes on to ask how this should impact on healthcare services and notes that the assessment process can be modified to incorporate an assesment of characteristics important for well-being. He also considers interventions including CBT, mindfulness-based therapy, narrative therapy and positive psychotherapy.

The last section on societal implications is very interesting and I would recommend a close reading of this section. Here is just one of the interesting insights from this section

‘This opens up innovative environmental approaches to fostering well-being, like the simple act of closing most points of entry to a housing estate which led to an increased sense of community and a 25% reduction in mental illness rates‘

In conclusion, I thought Slade’s article was extremely interesting, rich in content and filled with evidence-based approaches that have the potential to have significant benefits for society. These approaches may well cause a re-evaluation of the ways in which healthcare are delivered and a recognition of this emerging movement which complements the management of illness is essential for a better understanding of the delivery of healthcare in the 21st century.

References

Slade M. Mental Illness and Well-Being: The Central Importance of Positive Psychology and Recovery Approaches. BMC Health Services Research. 2010. 10:26.

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The paper reviewed here is ‘Brain Folding and the Size of the Human Cerebral Cortex’ by Paus and colleagues. In the abstract the authors state that

‘The expansion of the cerebral cortex, and in particular that of its prefrontal region, is a major evolutionary landmark in the emergence of human cognition. Our results suggest that this may be, at least in part, a natural outcome of increasing brain size‘

In the introduction, the authors write that when the logarithmic function is applied to the ratio of the surface area of the cortex to the cortical volume there is a linear result. However humans buck the trend with their expansion of both cortical volume and cortical folding and the resulting ratio. The researchers have developed a novel method for estimating the degree of cortical folding which they use here.

Methods

Firstly the researchers have used a 1 Tesla MRI scanner for structural Magnetic Resonance Imaging. Using T1 weighted images they have acquired ‘140-160 saggital slices’. The subjects for the study were from the Saguenay Youth Study. In the initial phase they included the results from 408 people aged 12-20. After exclusion of scans were cortical thickness could not be reliably estimated the images from 314 subjects remained (164 female 140 male). I couldn’t identify the method by which they excluded images in this manner which thus acts as an inclusion criterion. It would be interesting to see if those excluded could be characterised. The demographics otherwise are not included in this paper although they cite another paper in which the original study was reported. The age range within these subjects is fairly narrow and I was surprised to see no significant age related changes in either the hemispheric surface area or hemispheric volume given that this is a relatively important stage in development (although it was obviously not longitudinal).

A critical part of the study was the use of the novel method for estimating cortical folding. The authors identify the method they use for these purposes. They firstly identify a point on the cortical surface. I wasn’t clear on how this was identified. This might seem a somewhat trivial point but there are in theory an infinite number of points on the cortical surface. For instance if we choose two points on the cortical surface we can take another point midway between them and then repeat this ad infinitum. I presume there are some limitations here determined by the pixel resolution of the scanned image. Moving onto the next stage, the researchers then use the point to construct both a sphere and a circle. At this stage I was slightly confused. The researchers are using the ratio of the pial surface area to that of the disc to produce the ratio of interest. However since it is a sphere that is being considered I was not clear if they were rotating the disc within the sphere and repeating the calculations for each part of the rotation. If so, how many rotations are being performed (presumably the volume is being sampled from a finite number of rotations). Furthermore I was unclear on how the surface area was calculated. It seemed as though the most sensible way was for the software to divide up the circle into small squares and count how many of them were filled and estimate the fill from these. The smaller the squares used for the image the more accurate would be the results.

Results

I wasn’t clear on the meaning of the described formula for estimating cortical folding and so felt a bit uncomfortable reading the results as I could have misinterpreted their meaning. Essentially the researchers go on to state their findings that in larger brains there was a greater degree of folding, that the cortical folding was most pronounced in the prefrontal cortex and then infer that in humans, the pronounced cortical folding in the prefrontal cortex may be a result of the large increase in cortical volume relative to other species.

Conclusions

The researchers’ stated results are undoubtedly interesting although as stated above I haven’t fully understood the meaning of the technique that was used to determine this. This part of the method is described in a number of lines and has an accompanying diagram although I would have preferred a more detailed description spelling out the individual steps. However it may be that other readers were able to understand this without too much difficulty or that there are space restrictions in a printed version of the journal. Here I had a thought. Perhaps it would be useful if in the medical sciences (and biological sciences) researchers were able to record a video of their methodology. This could be encouraged by the journals. Recording a video of the methodology could be accomplished using a digital camcorder. If there is not one available in the department it could be obtained from another department. If even this is not available then a mobile video camera could be used. The video could then be uploaded onto YouTube provided it is 10 minutes or less, or if more then it could be broken down into a series. Once on YouTube, the audience would be able to see a more detailed explanation and demonstration of the techniques that are being used. The ability to use comments on YouTube would make this quite interactive and rapidly so. If sufficient videos of this nature are uploaded then certain videos explaining a particular methodology might prove more successful and researchers could simply refer to that video rather than duplicate the material. In this manner, the audience of the scientific paper would have a better understanding of the approach and the scientists and journals would have a powerful tool for communicating the science overcoming the restrictions of a paper based medium alone.

References

Toro R, Perron M, Pike B, Richer L, Veillette S, Pausova Z and Paus T. Brain size and folding of the human cerebral cortex. Cerebral Cortex. 2008. 18. 2352-2357.

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

These two tasks activated the supplementary motor area (SMA) (motor task) and parahippocampal gyrus (PHG) (spatial task) respectively. The researchers then asked all subjects to associate the motor task with yes and the navigation task with no. They were careful to ensure that the subjects attended to these tasks with a period of sustained attention so that the signal could be distinguished from that associated with more automatic responses. This was done in order to increase the likelihood that the activity represented ‘conscious’ activity. The tasks were repeated on 5 occasions to increase the reliability of the data after averaging the signals.

They then presented subjects with autobiographical questions. I wasn’t clear on whether the questions varied from one subject to another. They were then asked to think the correct response – a yes or a no by means of the associated imagery. The researchers averaged the activity for the imagery tasks. They averaged the activity for the responses to questions. They identified the ‘centre’ of the activity for both tasks and calculated the distance of the centres of activity from each other to produce a ’similarity’ score. The ability of a person to produce activity in the SMA or PHG in response to the researcher’s instructions was inferred as evidence of the will (although perhaps an interruption of auditory or semantic processing may interfere with task responses also). Of 54 patients in the study with a clinically recognised vegetative state, in 5 of those people activity in the appropriate areas were associated with the researchers’ instructions on the imagery tasks. However when it came to the autobiographical questions, only 1 subject produced activity associated with the correct responses. In this subject the expected activity for correct responses was identified in 4 out of 5 of the autobiographical questions.

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

A recent relatively small study in the Archives of General Psychiatry looked at people with schizophrenia (n=8) and compared them with controls (n=8). They used structural imaging to compare the hippocampal volume after a program of aerobic exercise. There was found to be 12% increase in hippocampal volume in the people with schizophrenia and a 16% increase in the control group adding to the evidence base for the benefits of exercise in both health and illness (see also the book reviewed in this post).

Electroretinography has been used to investigate healthy people with a family history of schizophrenia or bipolar disorder and the researchers have found preliminary evidence of a reduction in the responsiveness of the rods in the retina. They compared 29 people with a family history of either Bipolar Disorder or Schizophrenia with 29 healthy controls without a family history of these disorders. They found a significant difference on one of the amplitude measures (23%)(p<0.0001). The researchers interpreted this as suggesting a possible genetic basis for an alteration in the early stages of sensory processing. However it will be interesting to see if these findings are replicated in larger studies and if so then it will complement other lines of evidence showing a relationship between altered perceptual (rather than sensory) processing in the cortex and psychopathology.

Researcher Kausak Si teamed up with Eric Kandel to investigate the role of a protein called CPEB in slugs. The CPEB is located in neuronal synapses. When the researchers targetted antibodies to CPEB they interfered with the ability to form new memories. They found that CPEB was similar to prions found in Yeast and have speculated that self-replication might play a role in memory formation (although they didn’t have evidence from this study for that particular hypothesis). Prions have been identified in a number of pathological conditions including Creutzfeld-Jacob disease. rather than in health.

News Round-Ups

MindHacks has another spike activity including a link to an article about the recent study showing evidence of grid cells in humans.

Psychiatry 2.0

The Frontier Psychiatrist has a very interesting interview with psychiatrist Dr Iain McGilchrist

Evolutionary Psychiatry

Music has a strong relationship to language and recent research covered here highlights the close relationship between the two. This relationship has a number of possible implications in a wide number of areas which involve language. A recent study (from a few months back) looked at music appreciation in cotton-top tamarins (a form of New World monkey) and the researchers found that they were responsive to music written specifically for them but not to human music. The music can be heard at the link above and was based on the tamarin’s own calls and other vocalisations. For anyone curious about what cotton-top tamarins look like, I’ve made two short videos (here and here).

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The podcasts reviewed here are the 13th and 14th episodes in Hoegen’s MindPodcast series. In Episode 13 (available here), Hoegens discusses perception. He looks initially and very briefly at agnosia before turning to Gestalt theory. Hoegens discusses figure-ground articulation with reference to a polar bear in the ice. He also looks at several gestalt principles including proximity and closeness  using the example of moving lights. The link to the grouping principle wasn’t working at the time of testing but there is an interesting post for further reading over at Scholarpedia (see here). In Episode 14 (available here) Hoevens looks at a number of perceptual theories – using templates, top down and bottom up approaches. Hoeven’s material in this episode is very good and he’s obviously read widely around this subject which is also quite abstract but of relevance to many areas. He details the use of templates and points out one of the difficulties with this theory. He then looks at a number of variations on the bottom-up theories proposed by people such as Marr before finishing with a look at top down approaches and the mixing of the two in practice. 1 of the 5 links in the post was broken which is remarkable given that the post was published in 2005! The links provide the reader with examples of optical illusions to support the main material. Hoegens retains the familiar and effective formula of a relaxed discussion with Baroque music playing quietly in the background.

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The blog reviewed here is the ‘O’Really’ blog. I was first directed to this blog by Hope Leman author of the Significant Science blog (see review here).  The blog is by Duncan Hull, a software engineer at the European Bioinformatics Institute.

Appearance and Design

In order to move through the blog, the reader must move to the bottom of the page and click on ‘next page’. This is a very quick method for getting to recent articles but is slightly trickier for much older articles. There is an outer gray-white graded background and the articles lie on a white background with black font in the main body of the text and blue title font and blue hypertext links. The articles are accompanied by small pictures. Top posts and recent comments are visible on the right hand side of the screen.

Content

The first post I could identify is from May 2006 and which informs the reader of an impressive programme catalogue built up by the BBC in relation to it’s archive of radio and television programmes. The details of the creative commons license used for this blog are also outlined in this initial page. There’s a great question in this article which is can there be too many databases. I thought that Hull’s concept in this article is very creative – the visual representation of bionformatics using familiar solutions (but familiar in another context). This post ‘Who owns science?’ is neat and reflects on the nature of science in terms of various interested groups. There were a few useful links such as this one to chemical entities of biological interest and also a description of the open biomedical ontologies.

Conclusions

This is an accessible blog which covers some tricky bioinformatics topics in a relatively non-technical style enabling Hull to reach a wider audience. There are a variety of article categories ranging from reports on conferences through to a discussion of databases. I found a number of the articles to be highly original, exploring topics in detail and presenting a different spin on familiar subjects.

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The audiobook reviewed here is ‘Darwin and Evolution (Unabridged)’ by Dr Michael Ghiselin and narrated by Edwin Newman. Firstly Edwin Newman the narrator speaks clearly and slowly and the rich timbre of his voice conveys a sense of authority as well as maintaining the interest of the listener. There are a number voices for figures portrayed in the book including Darwin and Linnaeus which I thought was quite creative and again maintains interest for the listener. As the audiobook is relatively brief at just under 3 hours and as there is a great deal of material to cover, I was impressed at Ghiselin’s ability to do so concisely by conveying the essence of Darwin’s theories including quotes from Darwin himself. Ghiselin gives a background to the other important figures in the story which include Linnaeus, Huxley (nicknamed ‘Darwin’s bulldog’), Owen, Wilberforce and Wallace who was due to publish a theory of evolution himself and had apparently received ideas by reading Darwin’s book on the ‘Voyage of the Beagle’ (see review here).

I was interested to hear quotes from Darwin placed strategically close together in the book and explaining some of his thoughts behind natural and sexual selection quite clearly. Ghiselin goes onto describe some of the developments after Darwin’s death. I was surprised to find that sometime later that there had been a loss of interest in Darwin’s theory of natural selection and that a resurgence occured after this. What was also interesting was that Darwin had in his time addressed many of the alternatives to natural selection and rebuffed them with appropriate evidence, alternative theories that continue to be proposed albeit in different forms. Ghiselin discusses the work of Haldane in reconciling genetics and natural selection

I thought this was a well constructed audiobook which concisely explains essential features of Darwin’s important theories and I thought it was sufficiently informative to be useful for repeated listening.

References

Dr Michael Ghiselin. Darwin and Evolution (Unabridged). Narrated by Edwin Newman. Blackstone Audiobooks. 1993.

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The article reviewed here is ‘Risk factors for Dementia’ by Jen-Hua Chen and colleagues and freely available here. The authors begin with an introduction to dementia and the prevalence of the main types. They then outline the methodology for the paper identifying the databases used and the search period. However there is no mention of the search terms that were used and the search strategy beyond this including exclusion criteria for considered papers. The authors do not state the number of papers identified. They begin with a look at genetics including the strong associations with the APOE4, presenilin-1 and presenilin-2 genes. Presumably due to the submission date they have missed out on the recent findings from the Genome Wide Association studies last year showing three new candidate genes. In the next section they identify the strong association with age as well as looking at some of the controversy over an association with parental age at birth. Gender differences in prevalence are then examined and figures are cited showing that these vary between countries. The authors then discuss some of the evidence showing a strong protective effect for physical activity against dementia and cognitive decline in dementia. The controversies over smoking are discussed and the need for further studies (there was a study from last year which I thought provided convincing evidence against smoking as a protective factor in dementia for instance).

They then discuss the role of drugs as risk factors and include some evidence of benzodiazepine use as a risk factor while also mentioning some conflicting evidence for statins before moving onto antihypertensive medication which is quite topical given a paper published in the BMJ last month. They then discuss some further conflicting data on a potential protective role of HRT and NSAIDS. I think that the antihypertensive medication that is getting a lot of attention at the moment. The protective role of education is discussed briefly but there is probably an interesting story behind this association that is yet to be told. The authors identify the controversies in the evidence for alcohol use as protective factor and they suggest that focusing on wine rather than considering all types of alcohol together would address some of the conflicting findings. The authors identify a differential relationship between BMI and risk of dementia according to age stratifications. The section on comorbidity is brief and after considering some associations they speculate that inflammatory pathways might represent a common theme on the basis of two meta-analyses. They then consider environmental factors lumping together exposure to metals and diet. Again there has been more recent evidence of a protective role of the Mediteranean diet which might have just missed the submission date. Factors such as social relationships are not considered.

This is a brief review in which the authors group risk factors into a number of useful categories and this would be a starting point for a more definitive treatment of the subject.

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I have been invited to preview a new feature on Medpedia and to let my readers know about this feature. Readers can now access information in the Clinical Trials database from Medpedia. The database is accessible from sites such as PubMed. However the neat point in Medpedia is that the database interface is embedded in the encyclopedia articles themselves. So for instance, a quick search for Alzheimer’s Disease produces the following article here. On the top right hand corner of the page there is a hypertext link to the Clinical Trials database interface. Clicking on this link takes the reader to another page which lists 604 articles at the time of writing, a number of which are displayed on the page. The search interface is also displayed on the page so that the searches can be further refined. The bottom line is that the information on clinical trials is available in a single mouse click from the article page which enables information to be rapidly identified. The idea behind this is to raise the visibility of clinical trials particularly those that are recruiting (see press release here). Published articles based on the clinical trials are also displayed as references which is another neat feature.

Conflict of Interest

The articles in this blog appear in the News and Analysis section of Medpedia

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On twitter I came across the following article posted by Maria Page. The article is ‘Development of Structure and Function in the Infant Brain: Implications for cognition, language and social behaviour’ by Paterson and colleagues and freely available here. Since developmenal processes in the infant brain are integral to many aspects of the adult brain I thought this was a very interesting article for consideration of both the infant and adult brain. In the abstract, the authors state that

‘This paper aims to provide an overview of four domains that ahve been studied using techniques amneable to elucidating the brain/behaviour interface: language, face processing, object permanence and joint attention, with particular emphasis on studies focusing on early development‘

On reading the paper I wasn’t able to identify a methodology section although this isn’t always used in review papers. I was impressed however by the highly structured layout of the paper and the abundance of interesting ideas resulting from consideration of overlap of different methodological approaches and research findings.

In the introductory section, the authors discuss the importance of considering multiple lines of evidence in producing an understanding of the relationship between mind and brain during the developmental process. They identify a number of established and emerging imaging techniques of varying degrees of temporal and spatial resolution. They discuss briefly some of the findings on the sequence of myelination of different brain regions. They also consider the use of examination of changes in neuropsychological function with time in providing part of the necessary information to answer the questions posed. The subsection on the relationship between brain and social behaviour is slightly more complex and it will be interesting so see how this develops as the nature of social behaviour and related phenomenon (e.g social cognition) become better characterised.

I found the section on auditory processing to be particularly useful with the findings from electrophysiological studies providing interesting findings. Some of these findings are further supported by functional and structural neuroimaging studies. The section on the planum temporale reminded me of some of the discussion used in Crow’s theory of schizophrenia. In the section of face processing, the authors provide evidence that this occurs in subcortical structures in early development and then switches to other networks identified in adult studies. I was intrigued as to whether some of the findings of face processing in infants were confounded by the changes in general aspects of visual processing between 6 and 12 months although these will have most likely been controlled within the studies.

In the test of object permanence I was intrigued by the description of the experimental paradigm as this was similar to aspects of a classic ‘theory of mind’ task in which the child must discern where an object is hidden but in doing so must anticipate where fictional characters have placed the objects. In this discussion of a more basic task, the authors emphasise that this is a test of short-term memory (STM) and is used in the assessment of cognitive impairment. Again the ‘theory of mind’ tasks will no doubt have controlled for cognitive impairment although I must admit I haven’t thought specifically about STM in my previous reading of these studies. The EEG findings in the frontal cortex I thought were also interesting. I found it trickier to interpret the findings in the section on attention other than to note that they focus on visual and auditory pathways. Could these be more generally described as perceptual rather than attention pathways?

The authors then integrate the material in their general discussion. While the paper is from 2006 and there will have been many advances in understanding of the topics discussed here, an integration of findings from multiple lines of evidence offers the opportunity of triangulation and the possibility of identifying more robust assumptions for model building. Another interesting aspect of this paper was that the authors have considered not just a static model of the relationship between mind, behaviour and brain but a dynamic one introducing a temporal course to the proceedings. This makes it not only more complex but also more aligned to the reality of the changes that occur during the course of child development and beyond. To assume for instance that the adult brain should be considered a static structure would be a mistake as the transition to old age occurs.

This is a complex and interesting way of looking at the relationship between mind, behaviour and brain and it will be useful to reinterpret some aspects of this paper in light of more recent advances in imaging.

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The paper reviewed here is ‘Hypocretin/orexin Disturbances in Neurological Disorders’ by Rolf Fronczek and colleagues. The search strategy is not described, but the authors state in the abstract

‘In this paper we first review the current methods to measure the integrity of the hypocretin system in human patients‘

and also write that they will be looking at the findings in a number of neurological disorders. There is a relatively brief introduction before the authors discuss the form and function of the hypocretin system including the alternative name of orexin and the production of hypocretin within the dorsolateral hypothalamus. They then discuss the techniques for assessing the function of hypocretin and here the reader is able to see the complexity involved as measurements in the CSF, in brain tissue and assessment of hypocretin containing neurons all have their own difficulties. Further there are reasons why there may not be a simple relationship between these measures and the function of hypocretin. Indeed it becomes apparent through the review that the issue of partial depletion of hypocretin does not always result in the expected physiological consequences.

They then look at a number of disorders starting with Narcolepsy. Essentially the findings of an association between hypocretin deficiency and narcolepsy. In particular the authors note that it is narcolepsy with cataplexy that hypocretin deficiency is strongly associated. They then look at a number of disorders included amongst which are Huntington’s Disease, Parkinson’s Disease, Alzheimer’s Disease, Lewy Body Dementia and Progressive Supranuclear Palsy. From their discussion I found the described results of a reduction in hypocretin in late stage Parkinson’s Disease and in post-mortem studies in Alzheimer’s Disease the most convincing. They cite one study of reduced hypocretin levels in multiple sclerosis with hypothalamic involvement, with the levels increasing after treatment with steroids. They also discuss Guillan Barre syndrome and traumatic brain injury.

They finish with a discussion of the possible functional relevance of partial hypocretin depletion and point out the difficulties of fully establishing a causal pathway between the reduction in hypocretin and physiological associations. They suggest that studies with a hypocretin agonist would be useful in this regards. I thought this was a well written article which introduces the reader to the subject area and provides a clear structure for reviewing the research that has taken place. The association with narcolepsy with cataplexy seems quite convincing and the associations with Parkinson’s Disease and Alzheimer’s Disease were quite interesting although this would be one of many pathophysiological pathways in these conditions.

References

Fronczek R, Baumann C, Lammers G, Bassetti C and Overeem S. Hypocretin/orexin Disturbances in Neurological Disorders. Sleep Medicine Reviews. 2009. 13. 9-22.

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Research in Dementia

There have been a number of interesting developments in therapeutics. A neurosurgical study is underway which involve gene therapy for Alzheimer’s Disease. A nerve growth factor will be delivered to cells in the Basal Nucleus of Meynert using an adenovirus vector. A drug 7,8-dihydroxyflavone has been identified which acts on the trk receptors just as Brain Derived Nerve Growth factor does and may therefore stimulate neurogenesis and it will be interesting to follow further studies in this area. A molecule Nmnat2 has been identified which is necessary for survival of neurons in vitro. Increasing levels of this molecule was associated with protection of neurons against insult.

Lansoprazole, more commonly used in the treatment of gastro-oesophageal reflux and gastric ulcers has found a new use this time for research in Alzheimer’s Disease. Lansoprazole has been found to bind to a pathological form of tau-protein which is found in the plaques associated with Alzheimer’s Disease and it’s use as a radioligand in PET studies is now being investigated.

Research in Alcohol Dependence

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

Research in Mood Disorders

There are preliminary reports that a proprietary combination of Buspirone and Melatonin – BCI-952 is effective in people with depression on the basis of a 6-week trial (n=142) with various outcome measures although this is a press release and it will be useful to see the study in more detail when it is formally published. The significance of this is that the combination has been shown in vivo to stimulate neurogenesis which is hypothesised to be a mechanism of antidepressant action.

News Round-ups

MindHacks has another episode of Spike Activity and includes links to a review of Jung’s Red Book and a mention of a pending meta-analysis on psychodynamic psychotherapy which apparently compares favourably other forms of psychotherapy on a range of disorders. The Clinical Cases and Images blog mentions a study comparing Lithium monotherapy, Valproate monotherapy and Lithium + Valproate in combination for prevention of Bipolar Disorder.

Psychiatry 2.0

The Hawaii Medical Association is now offering patients virtual appointments with doctors and this will no doubt be followed with interest by other organisations.

Evolutionary Psychiatry

One of the current questions in recent evolution is whether Neanderthals contributed to the human gene pool which would have many implications. A recent radiocarbon dating of a site in Portugal revises the date of the last Neanderthal remains to 37,000 years ago. This is significant in terms of the evaluation of a 30,000 year-old child’s skeleton which has properties of both Neanderthals and humans. In a recent study, Chimpanzees and Bonobos were compared on food tasks. The Chimpanzee infants performed differently to the Bonobos on tasks which involved identifying where food was located. The Bonobos were described as delayed in development relative to the Chimpanzees. Chimpanzees are more closely related to humans than Bonobos as Chimpanzees and Bonobos diverged some 1.3 million years ago. Slightly off-topic but the remains of a 7000-year old amputee in France shows evidence of surgical amputation without subsequent infection.

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The blog reviewed here is ‘Significant Science‘. In the About section, we learn that the author is Hope Leman and is intending to cover topics such as Health 2.0, Medicine 2.0 and Science 2.0 in the blog.

Appearance and Design

There is a white background and a central pane containing the articles. The articles consist of black text on a white background with light blue headings. At the time of writing, each page consists of several articles and the reader must scroll down to reach the index. The index allows the reader to navigate the blog by month or category.

Content

The first article dated October 14th 2009 is a look at how social media such as twitter can be used to recruit subjects for research and Leman looks at a case study. A tremendous strength of Leman’s blog is that she takes the time to approach and interview people relevant to her main themes. So for instance, this post features an interview with Chris Tryzna from the MyClinicalTrials who explains how social media are being used in the recruitment of research subjects as well as discussing some of the broader aims of the website. There is another interesting interview here, this time with Jon Brassey about the trip database. There is a very interesting interview with e-patient Dave which includes a look at participatory medicine, the concept of involving patient communities in the process and this will undoubtedly be a very interesting area to follow. The subject of Open Science is the topic of discussion in this post which features an interview with Anthony Williams from ChemSpider, which is an open science project focusing on chemistry. I thought the methods used to overcome ‘linkrot’ were extremely interesting. So for instance, how do you deal with blog posts that have disappeared from the web but which you have linked to? Williams has an interesting solution. There is also another interesting interview here, this time with Cameron Neylon about open science and particularly open access. Incidentally there is a short video interview with Hope Leman here.

Conclusions

In conclusion, this is a  young blog which contains relatively few articles. However the articles are of a very high quality and usually involve interviews with influential figures in the open science/health movement. There is a lot of very useful information geared to those with an interest in open science. Leman has a good sense of who the key players are in this emerging area and if past articles are anything to go by this is the blog to follow to keep a finger on the pulse of the open science movement.

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