Monthly Archives: January 2010

Review: Hypocretin and Neurological Disorders

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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News Round-Up: January 2009 3rd Edition

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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Podcast Review: Mind Podcast Episodes 9 and 10

The podcast reviewed here is the Mind Podcast. In episode 9 Hoeve looks at hearing. This is a brief episode in which Hoeve introduces the reader to the auditory system covering the basic anatomy and physiology as well as looking at conductive and sensorineural deafness. In terms of the physiology he discusses the theories of neural coding of auditory information according to the position of the nerve cells as well as their firing frequency. In episode 10, Hoeve looks at taste and smell. He suggests that by listening to a large number of podcasts on psychology the listener can become a psychologist but I suspect that this is his sense of humour which would be in keeping with his relaxed style. This is a very brief episode and there is a focus on a few interesting findings about each – the adaptation of taste, the number of taste receptors, gender differences in sensitivity to certain smells and the effect of solutions on subsequent experience of ‘neutral’ taste stimuli. Again Hoeve provides a basic and very relaxed introduction to the material. I think for more advance listeners it can be useful to go over some of the basic concepts again as there is always scope for reinterpreting the basics after having assimilated more advanced knowledge depending on the listener’s needs.

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Blog Review: Significant Science

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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Book Review: The Meaning of Life: A Very Short Introduction (Unabridged)

The book reviewed here is ‘The Meaning of Life: A Very Short Introduction (Unabridged)’ by Terry Eagleton and narrated by Jan Snyder. Firstly the narrator’s voice has a rich timbre and he speaks slowly, clearly and is able to maintain the listener’s interest throughout. Eagleton’s choice of subject, the meaning of life, is a big subject and one which has impacted on certain forms of psychotherapy. While I might have missed this, my experience of listening to the audiobook several times was that it was difficult for me to understand the overall structure of the book. Broadly speaking Eagleton tackles the definitions of meaning and of life in order to better frame the question of the meaning of life. He introduces the reader to notable philosophers who have commented on the topics he is discussing such as Camus, Sartre, Wittgenstein and Russell. Having no training in philosophy and only a little background knowledge, I found that certain points were covered too quickly and assumed a certain knowledge of the reader as in the meaning of postmodernism. My experiences of the book differed markedly throughout. In some parts there were references to meaning in popular culture and I thought that some of the points had been much discussed in this forum. In other parts Eagleton argues cogently about meaning. What I found quite powerful was not the rational arguments but rather the experiences that they evoked. This caused me to speculate that philosophy doesn’t necessarily have to be about rational arguments as much as about using the stream of consciousness to identify valid truths in a way which can be reproduced by others. At the same time, I suspect that this suggestion has probably been discussed before  and who knows – even debunked. That is the difficulty of reading about a familiar subject which is being explored using an unfamiliar discipline but is balanced by the new insights that can be brought to bear on an understanding of that subject. Another suggestion by Eagleton is that our lives are imbued with meaning whether we agree or disagree with meaning itself. We are thus born into a world of meaning constructed by others.

There was one part which I disagreed with and that is his brief discussion of happiness and disability. I disagre with his assertion that disability must impact on happiness. Here the answer is to go on and speak to people with disabilities and find out what their experiences of happiness or satisfaction is. Various people have already done this and found that the relationship between disability and satisfaction with life is a complex one that is dependent on many factors (e.g. (van Campen and Cardol, 2009)). There are numerous examples of people with significant disabilities living fulfilling lives and indeed challenging prejudices in society has been important in this regards. This also shows the importance of evidence in challenging prejudices and the risks associated with reasoning dissociated from empiricism (at least as stated in this case). While Eagleton doesn’t draw any firm conclusions about meaning he does move towards the values of agape and happiness as reasonable values of choice and here I thought that this fitted with positive psychology (see reviews here and here).

In conclusion, Eagleton tackles a difficult question from multiple perspectives giving insights from philosophy and although there were a few points on which I had disagreements with Eagleton as above, I found this a useful starting point for further reading.

References

Terry Eagleton. The Meaning of Life: A Very Short Introduction (Unabridged). Narrated by Jan Snyder. Audible Inc. 2009.

van Campen C and Cardol M. When work and satisfaction with life do not go hand in hand: health barriers and personal resources in the participation of people with chronic physical disabilities. Soc Sci Med. 69(1). 56-60. 2009.

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Review: Mental Health Services in Mexico

The paper reviewed here is ‘Mental Health Services in Mexico’ by Berenzon and colleagues. This is a concise article which runs to just over 2 pages but which gives a useful overview of the subject. The authors describe the structure of health services in general which are broadly divided into three categories – those funded by social security for employees, private service providers for those able to afford it and provision for the poorest members of the population funded by the popular insurance scheme. Within this context, the mental health services operate and follow mental health policy and legislation from 1983 followed by a Mental Health Program of Action initiated i in 2001 and a National Health Programme that commenced in 2007. The article continues with a look at the resources in Mental Health Services, the organisation of these services, training in psychiatry, research and a look at future challenges. There were two items in the article that I found of particular interest. The first was a breakdown of resources sourced from the WHO  – 44 psychologists (presumably in mental health) per 100,000 of the population compared to 2.8 psychiatrists per 100,000 of the population. The authors have included a table that allows comparison with other countries in the Americas including the USA and Cuba both of which have substantially more psychiatrists and psychiatric beds per 100,000 of the population. The other point I found quite interesting was that in rural areas there is limited access to the psychiatrist and people may instead consult ‘traditional doctors and informal agents’. Discrepancies between rural and urban mental health care extend to other countries where solutions such as telehealthcare have been adopted in an effort to utilise limited resources more efficiently. The authors note the relative concentration of mental health resources in Mexico City. After reflecting on this, I thought it would be interesting to see what relationship exists between the size of a city and the proportion of a country’s mental health resources that are accessed by the same city. So for instance, is there a linear relationship between the proportion of mental health services and the proportion of the population contained within a city or is there a non-linear relationship (e.g quadratic). In practical terms, if the population density is higher then there might be less far for both parties to travel to the consultation which in turn might impact on DNA rates. On the other hand, patients might live further away from the consultation centres or it might take longer to travel to the centres meaning that this question would benefit from an analysis of the relevant data. Similarly could such issues impact on the type of research that is carried out in different locations. These types of questions could be important. For example if we wanted to compare services between countries, would we need to compare urban centres against urban centres and rural centres likewise against their counterparts in the country of interest.

The authors have written a concise article which raises a number of questions and allow for a relatively rapid (but limited) qualitative comparison of services between countries.

References

Berenzon, S, Senties H and Medina-Mora E. Mental health services in Mexico. International Psychiatry. Vol 6. Number 4. October 2009. pp93-95.

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Review: The Anterior Temporal Lobes and Semantic Memory

The paper reviewed here is ‘The Anterior Temporal Lobes and the Functional Architecture of Semantic Memory’ by Simmons and Martin. The authors review the evidence for three competing theories of the role of the Anterior Temporal Lobes (ATL) in semantic memory. There is no stated methodology for this review article but instead it appears to represent a review of the literature guided by the expertise of the authors in this area. This topic is potentially important for diseases such as semantic dementia. In the introduction, the authors outline three competing theories for the function of the ATL’s in semantic memory

1. The ATL links together areas in the brain containing semantic information

2.The ATL contains information about unique objects

3. The ATL stores ‘social conceptual information’

They then go on to explain some of the subtleties within these classifications including the neat idea that the temporal lobe might not actually store the information itself but could point to this information elsewhere – in effect acting as a signpost. They alos highlight the possible roles for the ATL’s in storing broad or narrow categories of objects and specific objects or broader categories of objects.

The authors then go onto look at the some of the neuropsychological evidence for the role of the ATM in semantic memory. They comment on studies with transcranial magnetic stimulation in which the lateral surface of the ATL is targetted and where there is an impairment in object naming response. However they note that the TMS can have effects areas other than those directly targetted and so it is difficult to confirm a simple causal relationship between the two. There are similar arguments with other types of study and they also outline some of the counterarguments that have been developed.

The authors then look at neuroimaging data particularly fMRI studies. There is a focus on the conclusions of these studies rather than the methodologies and so this would be a useful starting point for further reading. The results cited included

- ATL activation on viewing familiar faces

- ATL activation on viewing famous faces

- ATL activation on inferring mental states and emotions in others

- Right ATL activated on ‘viewing photgraphs depicting scens with moral connotations…versus nonmoral control scens’

- Right ATL activated in relation to ‘socal abstract concepts such as courage or generosity’

as well as a number of other findings. They comment that there are no direct comparisons of all three competing theories in a single neuroimaging study. In their conclusions, the authors suggest that comparisons of the different theories could be tested within the same study and also comment on the possibility of using alternative methodologies to test the theories. One suggestion which I thought was particularly interesting was the use of cortical surface recording. This has already proved useful in investigating the role of the speech and language areas and perhaps it might be useful in asnwering these types of questions.

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