Gene expression profiling suggests a link between common psychotic diseases

16 May 2005

A report in The Lancet [Tkachev, D. et al. (2003) Lancet 362, 798-805] identifies some defects in expression of myelin-related genes present in both individuals with schizophrenia and those with psychotic bipolar disorder (also called manic depression), two forms of mental illness with markedly distinct symptoms and treatments. Myelin is a substance produced by specialised cells (oligodendrocytes and Schwann cells) that coats nerve cell axons, allowing them to conduct impulses between the brain and other parts of the body. Tkachev and colleagues investigated oligodendrocyte-specific and myelin-associated gene expression in the prefrontal cortex of brains from patients with schizophrenia and bipolar disorder using two techniques, quantitative PCR and microarray analysis. Expression of many (but not all) of these genes was reduced in oligodendrocyte cells from the diseased brain samples relative to those from the controls, suggesting that oligodendrocyte function (particularly with respect to myelin production) was abnormal. The authors propose that the correlation between the gene expression changes in schizophrenia and bipolar disorder provide evidence for common pathological pathways in the two diseases.

Comment: The importance of oligodendrocyte cells and myelination in psychotic disease is reinforced by this study, and evidence for similarities between two quite distinct diseases is presented. The study size is small (only fifteen samples for each disease and for controls, and not all of these were included in the analysis of microarray data) and there is considerable scope for further investigation. A commentary by Davis and Harutunian on the report raises a number of pertinent questions to be addressed, including the issue of differences in gene expression in different regions of the brain; they suggest that regional patterns of altered gene expression might vary between the two diseases. They also query whether a similar overlap in gene expression would be observed between the brains of patients with schizophrenia and those with non-psychotic forms of bipolar disease.

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