Genetic overlap between psychotic experiences in the community across age and with psychiatric disorders

Wikus Barkhuizen,Angelica Ronald,Frank Dudbridge,Oliver Pain

doi:10.1038/s41398-020-0765-2

Abstract

This study explores the degree to which genetic influences on psychotic experiences are stable across adolescence and adulthood, and their overlap with psychiatric disorders. Genome-wide association results were obtained for adolescent psychotic experiences and negative symptom traits (N = 6297–10,098), schizotypy (N = 3967–4057) and positive psychotic experiences in adulthood (N = 116,787–117,794), schizophrenia (N = 150,064), bipolar disorder (N = 41,653), and depression (N = 173,005). Linkage disequilibrium score regression was used to estimate genetic correlations. Implicated genes from functional and gene-based analyses were compared. Mendelian randomization was performed on trait pairs with significant genetic correlations. Results indicated that subclinical auditory and visual hallucinations and delusions of persecution during adulthood were significantly genetically correlated with schizophrenia (rg = 0.27–0.67) and major depression (rg = 0.41–96) after correction for multiple testing. Auditory and visual subclinical hallucinations were highly genetically correlated (rg = 0.95). Cross-age genetic correlations for psychotic experiences were not significant. Gene mapping and association analyses revealed 14 possible genes associated with psychotic experiences that overlapped across age for psychotic experiences or between psychotic experiences and psychiatric disorders. Mendelian randomization indicated bidirectional associations between auditory and visual hallucinations in adults but did not support causal relationships between psychotic experiences and psychiatric disorders. These findings indicate that psychotic experiences in adulthood may be more linked genetically to schizophrenia and major depression than psychotic experiences in adolescence. Our study implicated specific genes that are associated with psychotic experiences across development, as well as genes shared between psychotic experiences and psychiatric disorders.

Highlights

Psychotic experiences resemble positive symptoms of psychotic disorders, such as paranoia, hallucinations, and cognitive symptoms, and have a median prevalence rate of ~7%–8% in the general population[1,2]
psychotic experiences and negative symptoms (PENS) traits during adolescence Summary statistics for adolescent PENS came from a mega-Genome-wide association studies (GWAS) of three European community samples (N = 6297–10,098)[20]: Twins Early Developmental Study (TEDS)[33], a community sample born between 1994–1996 in England and Wales; Avon Longitudinal Study of Parents and Children (ALSPAC)[34,35], a birth cohort from the United Kingdom born in 1991–1992; and Child and Adolescent Twin Study in Sweden (CATSS)[36] that recruited twins born in Sweden since 1992
Genetic correlations with psychiatric disorders For positive psychotic experiences in UK Biobank, auditory hallucinations were significantly genetically correlated with schizophrenia and depression, but not with bipolar disorder

Summary

Introduction

Psychotic experiences ( called “psychotic-like experiences”) resemble positive symptoms of psychotic disorders, such as paranoia, hallucinations, and cognitive symptoms, and have a median prevalence rate of ~7%–8% in the general population[1,2]. Schizotypy[3] is a related, older personality-based construct compared with psychotic experiences and negative symptoms (PENS). Positive psychotic experiences during adolescence or adulthood, especially when persistent, are associated with an increased risk of developing psychotic disorders[4,5,6,7,8,9] and, to a lesser extent, with other psychiatric disorders[10,11,12]. Schizotypy is associated with subsequently developing psychotic disorders[13]. Twin studies suggest heritability accounts for a third to a half of variation in PENS during adolescence[14,15,16,17,18,19]

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Results

Discussion

Conclusion