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European Child & Adolescent Psychiatry
Published in: European Child & Adolescent Psychiatry 3/2022

Open Access 01-03-2022 | Schizophrenia | Original Contribution

Schizophrenia polygenic risk is associated with child mental health problems through early childhood adversity: evidence for a gene–environment correlation

Authors: Koen Bolhuis, Lisa R. Steenkamp, Laura M. E. Blanken, Alexander Neumann, Philip R. Jansen, Manon H. J. Hillegers, Charlotte A. M. Cecil, Henning Tiemeier, Steven A. Kushner

Published in: European Child & Adolescent Psychiatry | Issue 3/2022

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Abstract

Previous studies have shown that schizophrenia polygenic risk predicts a multitude of mental health problems in the general population. Yet it is unclear by which mechanisms these associations arise. Here, we explored a possible gene–environment correlation in the association of schizophrenia polygenic risk with mental health problems via childhood adversity. This study was embedded in the population-based Generation R Study, including N = 1901 participants with genotyping for schizophrenia polygenic risk, maternal reporting of childhood adversity, and Child Behaviour Checklist measurement of mental health problems. Independent replication was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3641). Associations were analysed with Poisson regression and statistical mediation analysis. Higher burden of schizophrenia polygenic risk was associated with greater exposure to childhood adversity (P-value threshold < 0.5: Generation R Study, OR = 1.08, 95%CI 1.02–1.15, P = 0.01; ALSPAC, OR = 1.02, 95%CI 1.01–1.03, P < 0.01). Childhood adversities partly explained the relationship of schizophrenia polygenic risk with emotional, attention, and thought problems (proportion explained, range 5–23%). Direct effects of schizophrenia polygenic risk and adversity on mental health outcomes were also observed. In summary, genetic liability to schizophrenia increased the risk for mental health problems in the general paediatric population through childhood adversity. Although this finding could result from a mediated causal relationship between genotype and mental health, we argue that these observations most likely reflect a gene–environment correlation, i.e. adversities are a marker for the genetic risk that parents transmit to children. These and similar recent findings raise important conceptual questions about preventative interventions aimed at reducing childhood adversities.
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Metadata
Title
Schizophrenia polygenic risk is associated with child mental health problems through early childhood adversity: evidence for a gene–environment correlation
Authors
Koen Bolhuis
Lisa R. Steenkamp
Laura M. E. Blanken
Alexander Neumann
Philip R. Jansen
Manon H. J. Hillegers
Charlotte A. M. Cecil
Henning Tiemeier
Steven A. Kushner
Publication date
01-03-2022
Publisher
Springer Berlin Heidelberg
Keyword
Schizophrenia
Published in
European Child & Adolescent Psychiatry / Issue 3/2022
Print ISSN: 1018-8827
Electronic ISSN: 1435-165X
DOI
https://doi.org/10.1007/s00787-021-01727-4

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