Patients with higher polygenic risk scores (PRS) for schizophrenia tended to have less improvement with antipsychotic drug treatment, a recent study found. Therefore, PRS burden may have potential utility as a prognostic biomarker. All study subjects (4 independent cohorts of patients with first-episode psychosis, n=510) received initial treatment with antipsychotic medication for first-episode psychosis, and all were genotyped on standard single-nucleotide polymorphism (SNP) arrays imputed to the 1000 Genomes Project reference panel. PRS was computed based on the results of the large-scale schizophrenia genome-wide association studies (GWAS) reported by the Psychiatric Genomics Consortium. Researchers found:
- In the discovery cohort, higher PRS significantly predicted higher symptom scores at the 12-week follow-up (controlling for baseline symptoms, sex, age, and ethnicity).
- Higher PRS significantly predicted greater post-treatment symptoms in the combined replication analysis and was individually significant in 2 of the 3 replication cohorts.
- Across the 4 cohorts, PRS was significantly predictive of adjusted 12-week symptom scores.
- Patients with low PRS were more likely to be treatment responders than patients with high PRS.
Zhang J-P, Robinson D, Yu J, et al. Schizophrenia polygenic risk score as a predictor of antipsychotic efficacy in first-episode psychosis. [Published online ahead of print November 5, 2018]. Am J Psychiatry. doi:10.1176/appi.ajp.2018.17121363.
This Week's Must Reads
Cognition Impairment a Familial Disposition of MDD, JAMA Psychiatry; ePub 2018 Dec 26; Mackenzie, et al
Cognition in MDD and Aberrant Network Connectivity, J Psychiatr Res; 2019 Mar; Albert, Potter, Boyd, et al
Partner Criticism During Therapy for Recurrent MDD, Behav Res Ther; ePub 2018 Dec 21; Vittengl, et al
Study: Predictions of MDD Are Multifactorial, Depress Anxiety; ePub 2018 Dec 5; van Bronswijk, et al
Linguistic Analysis of Memories of People with MDD, PLoS One; ePub 2018 Nov 26; Himmelstein, et al
Must Reads in Schizophrenia & Other Psychotic Disorders
Motivational Deficits in Schizophrenia Examined, Cogn Affect Behav Neurosci; 2018 Dec; Hernaus, et al
Medical Comorbidity, Mortality in Schizophrenia, Schizophr Res; ePub 2018 Dec 6; Brink, et al
Illness Awareness in Older Adults with Schizophrenia, Am J Geriatr Psychiatry; ePub 2018 Oct 21; Cohen, et al
Smartphone Program Aids Patients with Schizophrenia , Schizophr Res; ePub 2018 Dec 11; Achtyes, et al
Polygenic Risk Score Can Predict Drug Effectiveness, Am J Psychiatry; ePub 2018 Nov 5; Zhang, et al