Polygenic Risk Score Predicts Treatment Resistance in Schizophrenia

By David Douglas

April 02, 2020

NEW YORK (Reuters Health) - A polygenic risk score (PRS) can help predict resistance to treatment with antipsychotic medication in schizophrenia, according to Scandinavian researchers.

As Dr. Maren Caroline Frogner Werner of Oslo University Hospital told Reuters Health by email, "The study points to disease-related genetics as an important factor determining treatment response and is a step towards disentangling the mechanism of treatment resistance."

Antipsychotics fail to work well for about a third of people diagnosed with schizophrenia, Dr. Werner and colleagues note in Schizophrenia Research.

Patients with such resistance "have more impaired functioning, poorer psychosocial adjustment, higher rates of hospitalization and represent a higher cost to society relative to antipsychotic responsive patients," the researchers add.

Recent genome-wide association studies have identified a large number of single-nucleotide polymorphisms (SNPs) associated with the disorder, enabling the generation of the schizophrenia PRS and thus providing a measure of genetic predisposition.

To examine whether this might shed light on treatment resistance, the researchers studied 321 patients diagnosed with a schizophrenia-spectrum disorder. Using consensus criteria they classified 108 as being resistant to antipsychotic medication and the remaining 213 as not being resistant.

Using binary logistic regression to investigate the association between PRS and treatment resistance, the team found a high PRS significantly predicted treatment resistance after adjustment.

The positive predictive value of the model was 61.5% and the negative predictive value was 71.7%. Of five SNP significance thresholds that the researchers tested, the association was significant in one.

The results, Dr. Werner concluded, "indicate that with more comprehensive genetic data, PRS can be utilized in tailoring treatment to individuals with schizophrenia, offering more effective treatment in an early phase."

SOURCE: https://bit.ly/2JhQq8R Schizophrenia Research, online March 14, 2020.