Independent Prediction of Child Psychiatric Symptoms by Maternal Mental Health and Child Polygenic Risk Scores

Lawrence M Chen; Irina Pokhvisneva; Marius Lahti-Pulkkinen; Tuomas Kvist; Jessie R Baldwin; Carine Parent; Patricia P Silveira; Jari Lahti; Katri Räikkönen; Vivette Glover; Thomas G O'Connor; Michael J Meaney; Kieran J O'Donnell

doi:10.1016/j.jaac.2023.08.018

Independent Prediction of Child Psychiatric Symptoms by Maternal Mental Health and Child Polygenic Risk Scores

J Am Acad Child Adolesc Psychiatry. 2023 Nov 15:S0890-8567(23)02185-8. doi: 10.1016/j.jaac.2023.08.018. Online ahead of print.

Affiliations

¹ Douglas Research Centre, McGill University, Canada; Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Canada.
² University of Helsinki, Finland; Finnish Institute for Health and Welfare, Finland; University of Edinburgh, United Kingdom.
³ University of Helsinki, Finland.
⁴ University College London, United Kingdom.
⁵ University of Helsinki, Finland; Turku Institute for Advanced Studies, University of Turku, Finland.
⁶ Institute of Reproductive and Developmental Biology, Imperial College London, United Kingdom.
⁷ University of Rochester, Rochester, New York; Wynne Center for Family Research, University of Rochester, Rochester, New York.
⁸ Douglas Research Centre, McGill University, Canada; Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Canada; Child and Brain Development Program, Canadian Institute for Advanced Research (CIFAR), Canada; Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research (A∗STAR), Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁹ Douglas Research Centre, McGill University, Canada; Ludmer Centre for Neuroinformatics & Mental Health, McGill University, Canada; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Yale Child Study Center, Yale School of Medicine, New Haven, Connecticut; Yale School of Medicine, New Haven, Connecticut. Electronic address: kieran.odonnell@yale.edu.

PMID: 37977417
DOI: 10.1016/j.jaac.2023.08.018

Abstract

Objective: Prenatal maternal symptoms of depression and anxiety are associated with an increased risk for child socioemotional and behavioral difficulties, supporting the fetal origins of mental health hypothesis. However, to date, studies have not considered specific genomic risk as a possible confound.

Method: The Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n = 5,546) was used to test if child polygenic risk score for attention-deficit/hyperactivity disorder (ADHD), schizophrenia, or depression confounds or modifies the impact of prenatal maternal depression and anxiety on child internalizing, externalizing, and total emotional/behavioral symptoms from age 4 to 16 years. Longitudinal child and adolescent symptom data were analyzed in the ALSPAC cohort using generalized estimating equations. Replication analyses were done in an independent cohort (Prevention of Preeclampsia and Intrauterine Growth Restriction [PREDO] cohort; n = 514) from Finland, which provided complementary measures of maternal mental health and child psychiatric symptoms.

Results: Maternal depression and anxiety and child polygenic risk scores independently and additively predicted behavioral and emotional symptoms from childhood through mid-adolescence. There was a robust prediction of child and adolescent symptoms from both prenatal maternal depression (generalized estimating equation estimate = 0.093, 95% CI 0.065-0.121, p = 2.66 × 10^-10) and anxiety (generalized estimating equation estimate = 0.065, 95% CI 0.037-0.093, p = 1.62 × 10^-5) after adjusting for child genomic risk for mental disorders. There was a similar independent effect of maternal depression (B = 0.156, 95% CI 0.066-0.246, p = .001) on child symptoms in the PREDO cohort. Genetically informed sensitivity analyses suggest that shared genetic risk only partially explains the reported association between prenatal maternal depression and offspring mental health.

Conclusion: These findings highlight the genomic contribution to the fetal origins of mental health hypothesis and further evidence that prenatal maternal depression and anxiety are robust in utero risks for child and adolescent psychiatric symptoms.

Keywords: ALSPAC; child development; fetal origins of mental health; maternal depression; polygenic risk score.

Grants and funding

UG3 OD023349/OD/NIH HHS/United States