“Polygenic risk scores represent the combined effects of many thousands of genetic variants across the entire genome, and better represent the very complex genetic nature of schizophrenia,” said lead study author Jian-Ping Zhang, M.D., Ph.D., an assistant professor at the Feinstein Institute for Medical Research, in a press release.
Zhang and colleagues first analyzed DNA samples from 510 patients with first-episode psychosis who were participating in one of four clinical trials testing antipsychotic medications (two trials in the United States and two in Europe). The researchers identified how many genetic variants associated with the risk of developing schizophrenia each participant had. The total number of variants was used to calculate a polygenic risk score. They next compared the patients’ PRS score with how well they responded to the assigned antipsychotic (which in these four studies included amisulpride, aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone). The patients were considered to have responded to treatment if they experienced a reduction of 50% or more in total symptom scores from baseline to the 12-week follow-up.
The researchers found that the higher the PRS score a patient had, the more likely he/she would not respond to antipsychotic medication. When the researchers grouped the patients from all of the trials according to high and low PRS scores, they found 60.9% of patients in the low PRS group responded to antipsychotics compared with 52.1% in the high PRS group. The difference was even greater when only the two clinical trials involving people of European ancestry were analyzed; combining these two cohorts, the response rate in the low PRS group was 61.8% compared with 45.8% in the high PRS group.
“The results we found open the door for ‘precision medicine’ approaches to psychiatry, and more specifically, the use of polygene scores as a new technology for the treatment of psychiatric disorders,” said study co-author Todd Lencz, Ph.D., also of the Feinstein Institute, in the press release.
For related information, see the Psychiatric News article “Genetic Variant May Foretell Cognitive Response to Antipsychotics.”
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