How Genes May Help Determine Response to Antipsychotic Medications

How Genes May Help Determine Response to Antipsychotic Medications

Posted: May 2, 2016
How Genes May Help Determine Response to Antipsychotic Medications

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Takeaway: New study identifies several natural genetic variations that influence how patients respond to antipsychotic medications.

 

People's genes may determine how they respond to medications for psychosis. In a new study published February 23, 2016 in Translational Psychiatry, researchers identified a number of naturally occurring genetic variations that appear to be associated with how people with psychosis respond to treatment with antipsychotic medication.

Antipsychotics are a common and essential part of treating psychotic illness. They diminish symptoms and the risk of relapse for many patients. However, some patients do not show improvements after taking antipsychotics.

Genetic variations linked with patient response to antipsychotic medicines are identified. Tweet >

In the new study, led by Jeffrey R. Bishop, Pharm.D., M.S., of the University of Minnesota in Minneapolis -- a 2008 NARSAD Young Investigator grantee – and colleagues scrutinized the genetic profile of 86 people who had had their first episode of psychosis. These people either had schizophrenia, psychotic bipolar disorder, or major depressive disorder with psychosis, and had minimal exposure to antipsychotics prior to the study.

The team monitored the patients’ response to treatment with antipsychotics for 4-6 weeks, and also explored whether there is a relationship between response and genetic variations. Whole-genome scans pinpointed GRID2, a gene thought to be related to glutamate signaling. Glutamate is the brain’s primary excitatory neurotransmitter and thought by some to be involved in psychotic disorders. People carrying a certain variation of the GRID2 gene were more likely to respond poorly to antipsychotics, the analysis showed. Follow up studies are needed to determine if this variant is directly responsible for these differences.

The researchers also looked at the genes highlighted in previous research and known to be involved with glutamate signaling. Here, too, the team found that variations in a gene called GRM7 were significantly associated with antipsychotic response.

Together, these findings lend support for the idea that genetic variation in glutamate system genes influence how people respond to antipsychotic medicines, the scientists said. Future research is needed to understand the how gene variations exert their influence upon response to the medicines, knowledge that in turn could lead to novel strategies for development of more effective antipsychotics.

Also contributing to this research were James L. Reilly, Ph.D. of Northwestern University Feinberg School of Medicine and a 2007 NARSAD Young Investigator grantee; Konasale M. Prasad, M.D. of Western Psychiatric Institute and a 2005 NARSAD Young Investigator grantee; Matcheri S. Keshavan, M.D. of Harvard Medical School and a 1997 NARSAD Independent Investigator grantee; and John A. Sweeney, Ph.D. of the University of Texas Southwestern Medical Center and a 1997 NARSAD Independent Investigator grantee