TY - JOUR

T1 - Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis

AU - Velthorst, Eva

AU - Froudist-Walsh, Sean

AU - Stahl, Eli

AU - Ruderfer, Douglas

AU - Ivanov, Ilyan

AU - Buxbaum, Joseph

AU - iPSYCH-Broad ASD Group, the IMAGEN consortium

AU - Banaschewski, Tobias

AU - Bokde, Arun L.W.

AU - Bromberg, Uli

AU - Büchel, Christian

AU - Burke Quinlan, Erin

AU - Desrivières, Sylvane

AU - Flor, Herta

AU - Frouin, Vincent

AU - Garavan, Hugh

AU - Gowland, Penny

AU - Heinz, Andreas

AU - Ittermann, Bernd

AU - Paillère Martinot, Marie Laure

AU - Artiges, Eric

AU - Nees, Frauke

AU - Papadopoulos Orfanos, Dimitri

AU - Paus, Tomáš

AU - Poustka, Luise

AU - Hohmann, Sarah

AU - Fröhner, Juliane H.

AU - Smolka, Michael N.

AU - Walter, Henrik

AU - Whelan, Robert

AU - Schumann, Gunter

AU - Reichenberg, Abraham

AU - Børglum, Anders D.

AU - Grove, Jakob

AU - Mattheisen, Manuel

AU - Werge, Thomas

AU - Mortensen, Preben Bo

AU - Pedersen, Marianne Giørtz

AU - Pedersen, Carsten Bøcker

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Hougaard, David M.

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Hansen, Christine Søholm

AU - Daly, Mark J.

AU - Neale, Benjamin M.

AU - Robinson, Elise B.

AU - Cerrato, Felecia

AU - Dumont, Ashley

AU - Goldstein, Jacqueline

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1038/s41398-018-0229-0

DO - 10.1038/s41398-018-0229-0

M3 - Journal article

C2 - 30258131

AN - SCOPUS:85054049851

VL - 8

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

IS - 1

M1 - 204

ER -