A systematic review of genome-wide research on psychotic experiences and negative symptom traits: new revelations and implications for psychiatry

Abstract

We present a systematic review of genome-wide research on psychotic experience and negative symptom (PENS) traits in the community. We integrate these new findings, most of which have emerged over the last four years, with more established behaviour genetic and epidemiological research. The review includes the first genome-wide association studies of PENS, including a recent meta-analysis, and the first SNP heritability estimates. Sample sizes of <10 000 participants mean that no genome-wide significant variants have yet been replicated. Importantly, however, in the most recent and well-powered studies, polygenic risk score prediction and linkage disequilibrium (LD) score regression analyses show that all types of PENS share genetic influences with diagnosed schizophrenia and that negative symptom traits also share genetic influences with major depression. These genetic findings corroborate other evidence in supporting a link between PENS in the community and psychiatric conditions. Beyond the systematic review, we highlight recent work on gene-environment correlation, which appears to be a relevant process for psychotic experiences. Genes that influence risk factors such as tobacco use and stressful life events are likely to be harbouring 'hits' that also influence PENS. We argue for the acceptance of PENS within the mainstream, as heritable traits in the same vein as other sub-clinical psychopathology and personality styles such as neuroticism. While acknowledging some mixed findings, new evidence shows genetic overlap between PENS and psychiatric conditions. In sum, normal variations in adolescent and adult thinking styles, such as feeling paranoid, are heritable and show genetic associations with schizophrenia and major depression.

Figure 1.

SNP heritability estimates and twin heritability estimates for psychotic experiences and negative symptom traits (PENS) in the community. SNP and twin heritability estimates come from the largest respective studies (1,23) and are shown with standard errors and 95% confidence intervals, respectively. For SNP heritability estimates, *P < 0.05; **P < 0.01.

Figure 2.

Polygenic risk scores for schizophrenia, bipolar disorder and major depression and their prediction of adolescent psychotic experiences and negative symptom traits (PENS) in the community from a recent meta-analysis (1). Published by John Wiley & Sons Ltd. © The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Publishing, Inc.