Researchers eye genetic factors in schizophrenia drugs

Mind over matter: A new study by Feinstein Institute researchers suggests genetic factors can help predict patients' response to pharmaceutical treatments for schizophrenia.
By GREGORY ZELLER //

A new study by Feinstein Institute for Medical Research scientists suggests that a patient’s response to antipsychotic pharmaceuticals can be predicted by genetic predispositions.

Schizophrenia – characterized by delusions, hallucinations and disorganized thoughts – is one of the leading causes of disability in the United States. Antipsychotic pharmaceuticals are a common treatment option, but such therapies are often “given without guidance from lab tests to show effectiveness, as is common in other areas of medicine,” according to the Manhasset-based Feinstein Institute, Northwell Health’s R&D division.

Doctors often employ “trial-and-error” protocols when selecting schizophrenia treatments, without knowing how or if a patient will respond – uncertainty that “places a large burden on not only patients and their families, but also healthcare professionals and healthcare system,” the institute added in a statement.

In findings published this week by the American Journal of Psychiatry, Feinstein Institute professor Todd Lencz and other investigators note that drugs used to treat schizophrenia can have varying effects on patients – but that certain reactions can be effectively predicted by studying genetics.

In the study, the Feinstein Institute team employed genetic tests to predict “ultimate response” to medications among patients suffering their first-ever schizophrenic episodes. Rather than testing for a single gene common among the patients, the researchers compiled “polygenic risk scores,” which “represent the combined effects of many thousands of genetic variants across the entire genome,” according to assistant Feinstein Institute professor Jian-Ping Zhang, listed as the study’s lead author.

Todd Lencz: Opening doors.

The polygenic risk scores also “better represent the very complex genetic nature of schizophrenia,” added Zhang, also a Donald and Barbara Zucker School of Medicine at Hofstra/Northwell assistant professor certified by the American Board of Psychiatry/Neurology.

The upshot: Patients with higher polygenic risk scores – signifying a greater “genetic burden” – were less likely to respond to conventional antipsychotic treatments. Two independent cohorts, conducted by Feinstein Institute scientists in concert with European researchers, supported the findings.

Feinstein Institute researchers now hope to expand on their work, with the ultimate goal of developing clinical guidelines for the use of polygenic risk scores and other predictors – including brain scans – in determining schizophrenia treatments.

“The results we found open the door for ‘precision medicine’ approaches to psychiatry,” Lencz said. “More specifically, the use of polygene scores as a new technology for the treatment of psychiatric disorders.”