New genetic link to schizophrenia

Feb 28 2008

Schizophrenia emerges from an altered pattern of brain development, and researchers continue to search for the genes that cause the brain to develop along a path that ultimately leads to schizophrenia.

In a high priority article to be published in Biological Psychiatry on March 1st, researchers report their findings on a new genetic link to schizophrenia.

A prior genetic mapping study indicated that a particular gene, multiple epidermal growth factor-like domains 10 or MEGF10, may be associated with schizophrenia. In this new paper, Chen and colleagues directly studied this particular MEGF10 gene in both schizophrenia patients and healthy control subjects. They found that a variant of the MEGF10 gene is associated with the heritable risk for schizophrenia in family-based and case-control genetic studies. Further, the MEGF10 gene appears to be expressed to a greater extent in post-mortem brain tissue from individuals diagnosed with schizophrenia compared to tissue from a group of unaffected individuals.

Dr. Xiangning Chen, corresponding author for this article and assistant professor of psychiatry and human genetics in the Virginia Commonwealth University School of Medicine, explains that “the significance of the paper is that it provides evidence that a gene, i.e. MEGF10, directly involved in apoptosis is found associated with schizophrenia. It has long been speculated that dysfunction of apoptosis may be a cause of schizophrenia, but there [has been] little direct evidence.” Apoptosis is an important biological process of programmed cell death in humans and other complex organisms, and abnormal apoptotic processes have been implicated in a variety of diseases.

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments on the curiosity of the association between schizophrenia and the MEGF10 gene, which influences the development of skin cells (the epidermis): “One clue may be that nerve cells and skin cells are derived from the same type of primitive cells early in the development of the embryo. Another link may be that features of epidermal development, such as the development of fingerprints, are abnormal in schizophrenia.“

The findings of this study indicate that it may be important for the field of schizophrenia research to more intensively study MEGF10, to understand how it influences brain development, and how it might be related to the treatment of schizophrenia.