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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Podcast

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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.

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.

Twitter

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Podcast

You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast).

TAWOP Channel

You can follow the TAWOP Channel on YouTube by clicking on this link

Responses

If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk

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.

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.

Twitter

You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link

Podcast

You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast).

TAWOP Channel

You can follow the TAWOP Channel on YouTube by clicking on this link

Responses

If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk

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.