S139. INVESTIGATING THE GENETIC ARCHITECTURE OF GENERAL AND SPECIFIC PSYCHOPATHOLOGY IN ADOLESCENCE USING SCHIZOPHRENIA POLYGENIC SCORES

Hannah Jones,Glyn Lewis,Peter Holmans,George Davey Smith,Jon Heron,Mary Cannon,David Ej Linden,Michael J Owen,James Walters,Peter B Jones,Gemma Hammerton,Stanley Zammit,Michael C O’Donovan,Jan Stochl

doi:10.1093/schbul/sby018.926

Abstract

BackgroundWhilst 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, something no studies have done to date. We examine how genetic risk for schizophrenia relates to a broad range of adolescent psychopathology using a latent modelling approach, and compare this to genetic risk for other psychiatric disorders, to gain a more comprehensive understanding of development pathways at this age.MethodsPRSs 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 relationships of these PRSs with psychopathology factors modelled within i) a correlated factors structure, and ii) a bifactor structure.ResultsThe schizophrenia PRS was associated with an increase in factors describing psychotic experiences, negative dimension, depression, and anxiety, but once modelling a general psychopathology factor 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.DiscussionPsychopathology 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.

Highlights

Suicidal ideation is a well-documented risk factor for suicidal behaviour, the majority of those with suicidal thoughts do not go on to make an attempt
Joint modelling is a useful statistical tool which can improve the prediction of the onset of psychosis and has the potential in guiding the provision of timely and personalized treatment to patients concerned
Auditory hallucinations (AH) and psychological distress (PD) are strongly associated with both suicidal thoughts and behaviour, but their role in the ideation-to-attempt transition has not been investigated in a longitudinal dataset

Summary

Results

Compared with the conventional approach of using only fixed predictors, joint modelling prediction models showed significantly better sensitivity, specificity and likelihood ratios. Discussion: Joint modelling is a useful statistical tool which can improve the prediction of the onset of psychosis and has the potential in guiding the provision of timely and personalized treatment to patients concerned. DO HALLUCINATIONS PREDICT THE TRANSITION FROM SUICIDAL THOUGHTS TO ATTEMPTS? RESULTS FROM AN AUSTRALIAN LONGITUDINAL COHORT STUDY. Hielscher*,1, Jordan DeVylder, Melissa Connell, Penelope Hasking, Graham Martin, James Scott1 1The University of Queensland; 2Fordham University; 3Curtin University

Background