Genetic variant predicts antipsychotic response for schizophrenia patients by ethnicity

Schizophrenia is a developmental disorder with a large genetic component contributing to increased risk.

Available antipsychotic medications treat some of the symptoms of schizophrenia, but are typically effective in only a subset of patients. Unfortunately, it is difficult to predict the effectiveness of a specific drug in any given individual with schizophrenia. John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, notes that “in this era of medicine, the selection of particular antipsychotic medications for particular patients with schizophrenia is more art than science. We have been seeking objective guides, perhaps biological tests, which would inform this process.” A new study published in the January 1st issue of Biological Psychiatry provides some interesting data to aid in that goal.

The authors report that differential effectiveness of antipsychotic treatment was predicted, in a subset of patients with schizophrenia, by variants of the gene encoding for the regulator of G-protein signaling 4 (RGS4), a protein that regulates the functional consequences of activating neurotransmitter receptors. Dr. Daniel Campbell, corresponding author for this article, explains these results: “By applying genetic analysis to the NIMH-funded Clinical Antipsychotic Trials of Intervention Effectiveness, we show that variants in a specific gene, RGS4, predict the effectiveness of different antipsychotic treatments. Our results also indicate that the predictive power of the RGS4 genetic variants differed between patients of self-reported African and European ancestry, and thus emphasize the importance of including multiple ethnic groups in a study.”

The authors importantly note that their results will require replication, but the findings indicate that RGS4 contributes to both the severity of schizophrenia symptoms and the response to antipsychotic treatment. Dr. Krystal adds, “While this type of information is not yet ready to guide clinical practice, since the RGS4 variants explain only a small component of overall patterns of treatment response, these data provide an example of “pharmacogenomics”, the approach that will very likely ultimately guide treatment.”