Schizophrenia polygenic risk score and 20-year course of illness in psychotic disorders

Katherine G. Jonas,Kaiqiao Li,Anil K. Malhotra,Roman Kotov,Laura J. Fochtmann,Evelyn J. Bromet,Todd Lencz,Greg Perlman

doi:10.1038/s41398-019-0612-5

Abstract

Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnosis and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β = 0.21), greater illness severity (β = 0.28), and worse cognition (β = −0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a tool for diagnosis and treatment planning.

Highlights

Introduction The SZPRS agglomerates the weighted effect of many single-nucleotide polymorphisms (SNPs) that discriminate schizophrenia cases from healthy controls[1]
There was an effect of the PRS on avolition (R2 = 0.11, β = 0.33, 95% CI 0.10–0.57, p < 0.01)
Among patients initially diagnosed with a psychotic affective disorder, a higher schizophrenia polygenic risk score (SZ PRS) predicted whose diagnosis would change to non-affective psychosis by the 20-year follow-up

Summary

Introduction

PRS agglomerates the weighted effect of many single-nucleotide polymorphisms (SNPs) that discriminate schizophrenia cases from healthy controls[1]. As the size of the PRS discovery cohort has increased, observed case–control variance explained has increased from 3 to 18%1,2. There is substantial heterogeneity in both the clinical presentation and illness course of schizophrenia that is difficult to capture in large studies. Longitudinal studies may reveal when and how the SZ PRS’s effects unfold. Edu) 1Department of Psychiatry, Stony Brook University, New York, NY, USA 2Departments of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, USA Full list of author information is available at the end of the article Jonas (Katherine.jonas@stonybrookmedicine. edu) 1Department of Psychiatry, Stony Brook University, New York, NY, USA 2Departments of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, USA Full list of author information is available at the end of the article

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Conclusion