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Maternal antenatal depression and child mental health: Moderation by genomic risk for attention-deficit/hyperactivity disorder

Published online by Cambridge University Press:  11 January 2021

Lawrence M. Chen
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada
Marieke S. Tollenaar
Affiliation:
Clinical Psychology Unit, Institute of Psychology, Leiden University, Leiden, the Netherlands Leiden Institute for Brain and Cognition, Leiden University, Leiden, the Netherlands
Shantala A. Hari Dass
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada
Andrée-Anne Bouvette-Turcot
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada
Irina Pokhvisneva
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada
Hélène Gaudreau
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada
Carine Parent
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada
Josie Diorio
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada Sackler Program for Epigenetics & Psychobiology, McGill University, Montreal, QC, Canada
Lisa M. McEwen
Affiliation:
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada
Julia L. MacIsaac
Affiliation:
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada
Michael S. Kobor
Affiliation:
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada Child and Brain Development Program, CIFAR, Toronto, ON, Canada
Roseriet Beijers
Affiliation:
Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition & Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
Carolina de Weerth
Affiliation:
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition & Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
Patricia P. Silveira
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada
Sherif Karama
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada
Michael J. Meaney
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada Sackler Program for Epigenetics & Psychobiology, McGill University, Montreal, QC, Canada Child and Brain Development Program, CIFAR, Toronto, ON, Canada Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research (A*STAR), Singapore
Kieran J. O'Donnell*
Affiliation:
Douglas Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Montreal, QC, Canada Child and Brain Development Program, CIFAR, Toronto, ON, Canada Yale Child Study Center & Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
*
Author for Correspondence: Kieran J. O'Donnell, Yale Child Study Center, 230 South Frontage Road, New Haven, CT 06519, USA. Email: kieran.odonnell@yale.edu

Abstract

Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 × 10−4, R2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 × 10−9, R2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health.

Type
Special Section 2: Early Adversity and Development: Contributions from the Field
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Maternal antenatal depression and child mental health: Moderation by genomic risk for attention-deficit/hyperactivity disorder
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