Postmortem data support link between gene and schizophrenia

Main Category: Schizophrenia
Article Date: 14 Sep 2005 - 0:00 PDT

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We have known for a long time that there is a genetic component to schizophrenia, but nailing down the gene(s) has not been easy. The disease is complex, with multiple genes and environmental factors thought to be responsible for its manifestation. Several genes have been linked to schizophrenia, and a new study on one of the candidates, by Linda Brzustowicz and colleagues (Rutgers University), just published in the international open-access journal PLoS Medicine, further implicates the CAPON gene.

The researchers had previously found a connection between CAPON and schizophrenia in families where the disease is common, and other groups had seen a similar connection in their samples. This was intriguing because CAPON is part of a molecular pathway that is active in the brain and which might play a role in diseases like schizophrenia. In the present study, Brzustowicz and colleagues examined postmortem brain samples for differences in CAPON gene activity between normal individuals and those with mental illness. And in their set of 35 samples each from individuals with schizophrenia, individuals with bipolar disorder, and individuals without mental illness, they found such differences.

Genes are templates for proteins (which make up the majority of active components in cells and body), and the researchers found that the CAPON gene is a template for two different proteins, a short form and a long form. The brain samples from patients with schizophrenia and bipolar disorder had higher levels of the short form than brain samples from patients without psychiatric illness. Moreover, these higher levels of the short version were predominantly seen in people with variants of the CAPON gene that had been previously linked to schizophrenia.

These results lend more support to the idea that CAPON is involved in schizophrenia. Given the cumulative evidence, it seems clear that further study of CAPON is justified. The findings by Brzustowicz and colleagues suggest that we need to learn more about the short version of CAPON, and specifically its presence and function in the brain.

Citation: Xu B, Wratten N, Charych EI, Buyske S, Firestein BL, et al. (2005) Increased expression in dorsolateral prefrontal cortex of CAPON in schizophrenia and bipolar disorder. PLoS Med 2(10): e263.

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