Preben Bo Mortensen

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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Eva Velthorst, Department of Psychiatry and Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, USA. eva.velthorst@mssm.edu.
  • ,
  • Sean Froudist-Walsh, Center for Neural Science, New York University, New York, NY, 10003, USA.
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  • Eli Stahl, Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • ,
  • Douglas Ruderfer, Vanderbilt Genetics Institute, Vanderbilt Epidemiology Center, Institute of Medicine and Public Health, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
  • ,
  • Ilyan Ivanov, Department of Psychiatry and Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, USA.
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  • Joseph Buxbaum, Department of Psychiatry and Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, USA.
  • ,
  • iPSYCH-Broad ASD Group, the IMAGEN consortium, Preben Bo Mortensen, Jakob Grove (members of -)

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.

OriginalsprogEngelsk
Artikelnummer204
TidsskriftTranslational Psychiatry
Vol/bind8
Nummer1
Sider (fra-til)204
ISSN2158-3188
DOI
StatusUdgivet - 26 sep. 2018

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