Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis

Bokde, Arun; Whelan, Robert; Froudist Walsh, Sean

doi:http://dx.doi.org/10.1038/s41398-018-0229-0

Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis

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s41398-018-0229-0.pdf (776.34 KB)

Date

2018

Authors

Bokde, Arun

Whelan, Robert

Froudist Walsh, Sean

Access

openAccess

Citation

Velthorst, E. and Froudist-Walsh, S. and Stahl, E. and Ruderfer, D. and Ivanov, I. and Buxbaum, J. and Banaschewski, T. and Bokde, A.L.W. and Bromberg, U. and Bÿchel, C. and Burke Quinlan, E. and Desriviÿres, S. and Flor, H. and Frouin, V. and Garavan, H. and Gowland, P. and Heinz, A. and Ittermann, B. and Paillÿre Martinot, M.-L. and Artiges, E. and Nees, F. and Papadopoulos Orfanos, D. and Paus, T. and Poustka, L. and Hohmann, S. and Fröhner, J.H. and Smolka, M.N. and Walter, H. and Whelan, R. and Schumann, G. and Reichenberg, A. and Bÿrglum, A.D. and Grove, J. and Mattheisen, M. and Werge, T. and Mortensen, P.B. and Pedersen, M.G. and Pedersen, C.B. and Mors, O. and Nordentoft, M. and Hougaard, D.M. and Bybjerg-Grauholm, J. and Bÿkvad-Hansen, M. and Hansen, C.S. and Daly, M.J. and Neale, B.M. and Robinson, E.B. and Cerrato, F. and Dumont, A. and Goldstein, J. and Stevens, C. and Walters, R. and Churchhouse, C. and Ripke, S. and Martin, J., Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis, Translational Psychiatry, 8, 1, 2018, 204-

Abstract

While psychotic experiences (PEs) are assumed to represent psychosis liability, general population studies have not been able to establish significant associations between polygenic risk scores (PRS) and PEs. Previous work suggests that PEs may only represent significant risk when accompanied by social impairment. Leveraging data from the large longitudinal IMAGEN cohort, including 2096 14-year old adolescents that were followed-up to age 18, we tested whether the association between polygenic risk and PEs is mediated by (increasing) impairments in social functioning and social cognitive processes. Using structural equation modeling (SEM) for the subset of participants (n = 643) with complete baseline and follow-up data, we examined pathways to PEs. We found that high polygenic risk for schizophrenia (p = 0.014), reduced brain activity to emotional stimuli (p = 0.009) and social impairments in late adolescence (p < 0.001; controlling for functioning in early adolescence) each independently contributed to the severity of PEs at age 18. The pathway between polygenic risk for autism spectrum disorder and PEs was mediated by social impairments in late adolescence (indirect pathway; p = 0.025). These findings point to multiple direct and indirect pathways to PEs, suggesting that different processes are in play, depending on genetic loading, and environment. Our results suggest that treatments targeting prevention of social impairment may be particularly promising for individuals at genetic risk for autism in order to minimize risk for psychosis.