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Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults

Childhood maltreatment (CM) and genetic vulnerability are both risk factors for psychosis, but the relations between them are not fully understood. Guided by the recent identification of genetic risk to CM, this study investigates the hypothesis that genetic risk to schizophrenia also increases the...

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Autores principales: Marchi, Mattia, Elkrief, Laurent, Alkema, Anne, van Gastel, Willemijn, Schubart, Chris D., van Eijk, Kristel R., Luykx, Jurjen J., Branje, Susan, Mastrotheodoros, Stefanos, Galeazzi, Gian M., van Os, Jim, Cecil, Charlotte A., Conrod, Patricia J., Boks, Marco P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160238/
https://www.ncbi.nlm.nih.gov/pubmed/35650188
http://dx.doi.org/10.1038/s41398-022-01975-1
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author Marchi, Mattia
Elkrief, Laurent
Alkema, Anne
van Gastel, Willemijn
Schubart, Chris D.
van Eijk, Kristel R.
Luykx, Jurjen J.
Branje, Susan
Mastrotheodoros, Stefanos
Galeazzi, Gian M.
van Os, Jim
Cecil, Charlotte A.
Conrod, Patricia J.
Boks, Marco P.
author_facet Marchi, Mattia
Elkrief, Laurent
Alkema, Anne
van Gastel, Willemijn
Schubart, Chris D.
van Eijk, Kristel R.
Luykx, Jurjen J.
Branje, Susan
Mastrotheodoros, Stefanos
Galeazzi, Gian M.
van Os, Jim
Cecil, Charlotte A.
Conrod, Patricia J.
Boks, Marco P.
author_sort Marchi, Mattia
collection PubMed
description Childhood maltreatment (CM) and genetic vulnerability are both risk factors for psychosis, but the relations between them are not fully understood. Guided by the recent identification of genetic risk to CM, this study investigates the hypothesis that genetic risk to schizophrenia also increases the risk of CM and thus impacts psychosis risk. The relationship between schizophrenia polygenetic risk, CM, and psychotic-like experiences (PLE) was investigated in participants from the Utrecht Cannabis Cohort (N = 1262) and replicated in the independent IMAGEN cohort (N = 1740). Schizophrenia polygenic risk score (SZ-PRS) were calculated from the most recent GWAS. The relationship between CM, PRS, and PLE was first investigated using multivariate linear regression. Next, mediation of CM in the pathway linking SZ-PRS and PLE was examined by structural equation modeling, while adjusting for a set of potential mediators including cannabis use, smoking, and neuroticism. In agreement with previous studies, PLE were strongly associated with SZ-PRS (B = 0.190, p = 0.009) and CM (B = 0.575, p < 0.001). Novel was that CM was also significantly associated with SZ-PRS (B = 0.171, p = 0.001), and substantially mediated the effects of SZ-PRS on PLE (proportion mediated = 29.9%, p = 0.001). In the replication cohort, the analyses yielded similar results, confirming equally strong mediation by CM (proportion mediated = 34.7%, p = 0.009). Our results suggest that CM acts as a mediator in the causal pathway linking SZ-PRS and psychosis risk. These findings open new perspectives on the relations between genetic and environmental risks and warrant further studies into potential interventions to reduce psychosis risk in vulnerable people.
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spelling pubmed-91602382022-06-03 Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults Marchi, Mattia Elkrief, Laurent Alkema, Anne van Gastel, Willemijn Schubart, Chris D. van Eijk, Kristel R. Luykx, Jurjen J. Branje, Susan Mastrotheodoros, Stefanos Galeazzi, Gian M. van Os, Jim Cecil, Charlotte A. Conrod, Patricia J. Boks, Marco P. Transl Psychiatry Article Childhood maltreatment (CM) and genetic vulnerability are both risk factors for psychosis, but the relations between them are not fully understood. Guided by the recent identification of genetic risk to CM, this study investigates the hypothesis that genetic risk to schizophrenia also increases the risk of CM and thus impacts psychosis risk. The relationship between schizophrenia polygenetic risk, CM, and psychotic-like experiences (PLE) was investigated in participants from the Utrecht Cannabis Cohort (N = 1262) and replicated in the independent IMAGEN cohort (N = 1740). Schizophrenia polygenic risk score (SZ-PRS) were calculated from the most recent GWAS. The relationship between CM, PRS, and PLE was first investigated using multivariate linear regression. Next, mediation of CM in the pathway linking SZ-PRS and PLE was examined by structural equation modeling, while adjusting for a set of potential mediators including cannabis use, smoking, and neuroticism. In agreement with previous studies, PLE were strongly associated with SZ-PRS (B = 0.190, p = 0.009) and CM (B = 0.575, p < 0.001). Novel was that CM was also significantly associated with SZ-PRS (B = 0.171, p = 0.001), and substantially mediated the effects of SZ-PRS on PLE (proportion mediated = 29.9%, p = 0.001). In the replication cohort, the analyses yielded similar results, confirming equally strong mediation by CM (proportion mediated = 34.7%, p = 0.009). Our results suggest that CM acts as a mediator in the causal pathway linking SZ-PRS and psychosis risk. These findings open new perspectives on the relations between genetic and environmental risks and warrant further studies into potential interventions to reduce psychosis risk in vulnerable people. Nature Publishing Group UK 2022-06-01 /pmc/articles/PMC9160238/ /pubmed/35650188 http://dx.doi.org/10.1038/s41398-022-01975-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Marchi, Mattia
Elkrief, Laurent
Alkema, Anne
van Gastel, Willemijn
Schubart, Chris D.
van Eijk, Kristel R.
Luykx, Jurjen J.
Branje, Susan
Mastrotheodoros, Stefanos
Galeazzi, Gian M.
van Os, Jim
Cecil, Charlotte A.
Conrod, Patricia J.
Boks, Marco P.
Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults
title Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults
title_full Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults
title_fullStr Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults
title_full_unstemmed Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults
title_short Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults
title_sort childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160238/
https://www.ncbi.nlm.nih.gov/pubmed/35650188
http://dx.doi.org/10.1038/s41398-022-01975-1
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