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

TitleMaternal antenatal depression and child mental health: Moderation by genomic risk for attention-deficit/hyperactivity disorder.
Publication TypeJournal Article
Year of Publication2020
AuthorsChen LM, Tollenaar MS, Dass SAHari, Bouvette-Turcot A-A, Pokhvisneva I, Gaudreau H, Parent C, Diorio J, McEwen LM, MacIsaac JL, Kobor MS, Beijers R, de Weerth C, Silveira PPelufo, Karama S, Meaney MJ, O'Donnell K
Corporate AuthorsMAVAN Study Team
JournalDev Psychopathol
Volume32
Issue5
Pagination1810-1821
Date Published2020 12
ISSN1469-2198
KeywordsAttention Deficit Disorder with Hyperactivity, Child, Depression, Female, Genomics, Humans, Mental Health, Mothers, Pregnancy
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.

DOI10.1017/S0954579420001418
Alternate JournalDev Psychopathol
PubMed ID33427178
Grant List / / Canadian Institutes for Health Research / International