Investigating the genetic architecture of general and specific psychopathology in adolescence

Abstract

Whilst associations between polygenic risk scores (PRSs) for schizophrenia and various phenotypic outcomes have been reported, an understanding of developmental pathways can only be gained by modelling comorbidity across psychopathology. We examine how genetic risk for schizophrenia relates to adolescent psychosis-related and internalizing psychopathology using a latent modelling approach, and compare this to genetic risk for other psychiatric disorders, to gain a more comprehensive understanding of the developmental pathways at this age. PRSs for schizophrenia, major depressive disorder, neuroticism and bipolar disorder were generated for individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Multivariate linear regression was used to examine the relationships of these PRSs with psychopathology factors modelled within (i) a correlated factors structure and (ii) a bifactor structure. The schizophrenia PRS was associated with an increase in factors describing psychotic experiences, negative dimension, depression and anxiety, but, when modelling a general psychopathology factor based on these measures, specific effects above this persisted only for the negative dimension. Similar factor relationships were observed for the neuroticism PRS, with a (weak) specific effect only for anxiety once modelling general psychopathology. Psychopathology during adolescence can be described by a general psychopathology construct that captures common variance as well as by specific constructs capturing remaining non-shared variance. Schizophrenia risk genetic variants identified through genome-wide association studies mainly index negative rather than positive symptom psychopathology during adolescence. This has potentially important implications both for research and risk prediction in high-risk samples.

Multi–Polygenic Score Approach to Identifying Individual Vulnerabilities Associated With the Risk of Exposure to Bullying

“…Regarding the lack of association between exposure to bullying and previously associated personality traits, 15,41 the PGSs used in this study were based on large studies (eg, based on GWAS samples >450 000 for irritability and >160 000 for neuroticism). Considering that such PGSs have been reported to contribute to child outcomes, 42 the lack of association unlikely reflects insufficient power. Instead, our findings suggest that some of the previously observed associations might be driven by co-occurring internalizing or externalizing symptoms.…”

The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence

“…Several studies have used polygenic scores for schizophrenia, ADHD and other psychiatric disorders to predict general psychopathology in childhood. An increasing amount of evidence converges on the finding that few polygenic effects specific to individual aspects of psychopathology remains after conditioning on the p factor (Brikell et al., ; Jones et al., , ; Riglin et al., ). These studies also suggest that genetic risk for psychiatric disorders emerges in childhood, in the form of continuously measured behaviour problems.…”

Genetic association study of psychotic experiences in UK Biobank

“…Whilst there was an initial assumption that psychotic experiences in adolescence would specifically increase the risk for schizophrenia, evidence suggests a nonspecific increased risk for a broader psychopathology 10 , suggesting that research on psychotic experiences may have an important role in understanding the pathway to a wide array of clinical diagnoses 5 . However, to date no study has found strong evidence for association between genetic liabilities for schizophrenia or any other mental disorder with psychotic experiences 7,8,[11][12][13] .…”