Crow on Genes in Schizophrenia

Today’s paper is by Professor Crow – entitled ‘Craddock and Owen v Kraeplin: 85 years late, mesmerised by polygenes’. The paper is a fairly brief one, running at 5 pages including the references and essentially allows Professor Crowe to state his position.

The question being asked is how should we view the psychoses – as a dichotomous form i.e. between schizophrenia and bipolar psychosis or as a single continuum. Professor Crowe suggests the latter. Indeed he writes that within the research community many of the people that contribute to the literature on classification support the concept of a continuum in schizophrenia.

Crowe quotes papers by Endicott (1982), Gershon and colleagues (1988), odegaard (1972) and Penrose (1991) in establishing the importance of affect in psychosis as well as the continuum theory. However in 1991, figures such as Murray, Tyrer and Roth are identified as supporting the binary model.

Crow then goes on to describe the essence of his theory which states that there is a continuum of psychosis which is secondary to an epigenetic phenomenon such as the binding of DNA by histones. This wouldn’t be detected through a linkage analysis. He further posits that this change would affect language which he adds is differently manifested in males and females and depends upon an asymmetry of the brain.

Model
Model

I had always been puzzled by the asymmetry argument. If an asymmetry of the brain was required, then how would a boy with a hemispherectomy have been able to attain language particularly after the critical learning period (This was a famous case about 8 years ago and I had asked this question at a presentation on lateralisation of brain function in language). The answer as I understood it was that the boy had been able to attain language but that it was apparently not fully developed although I know no more details than that.

Professor Crow’s review here is elegant. Within the space of a few pages, he has provided a succinct historical overview of the field as well as identifying key figures within the research area. He then provides supportive evidence for the continuum theory and finishes with his theory. The paper is a lesson in economy.

The model does however raise a few questions. Firstly if there is a small difference in the prevalence of schizophrenia between males and females, is this better explained by culture than by a fundamental biological difference. Secondly the recent genetic studies in Schizophrenia show an increase of up to 15-fold associated with genes in certain chromosomal regions. In this case, there is likely to be a clear gene linked cause in a small percentage of cases of schizophrenia. However, Crow’s model most likely refers to the more common causes of schizophrenia and there must be exceptions given the heterogeneity of the condition.

The model has great strengths in including recognised language difficulties in Schizophrenia as well as the results of linkage studies. The clarification of the specific causal pathway leading to language difficulties and schizophrenia will be very interesting and will most likely be of great clinical significance.

STT3

References

Crow T. Craddock and Own vs Kraeplin: 85 years late, mesmerised by “polygenes”. Schizophrenia Research. 103. 2008. 156-160.

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.

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