Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes

• Type of Material: Article
• Authors: Michael S. Breen, Icahn Sch Med Mt Sinai; Aliza Wingo, Emory University; Nastassja Koen, University of Cape Town; Kirsten A. Donald, University of Cape Town; Mark Nicol, University of Cape Town; Heather J. Zar, University of Cape Town; Kerry Ressler, Emory University; Joseph D. Buxbaum, Icahn Sch Med Mt Sinai; Dan J. Stein, University of Cape Town
• Language: English
• Date: 2018-10-01
• Publisher: Elsevier: 12 months
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbi.2018.05.016
• Title of Journal or Parent Work: Brain, Behavior, and Immunity
• ISSN: 0889-1591
• Volume: 73
• Start Page: 320
• End Page: 330
• Grant/Funding Information: Funding for the Drakenstein Child Health Study was from the Bill and Melinda Gates Foundation (OPP1017641); from the National Institutes of Health, USA (1U01MH115484-01); from the National Research Foundation, South Africa; and from the South African Medical Research Council (SAMRC).; The views and opinions expressed are those of the authors and do not necessarily represent the official views of the SAMRC.; Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under Award Number U01MH115484; and by the South African Medical Research Council under a Self-Initiated Research Grant.; APW is supported by the Department of Veterans Affairs Career Development Award IK2CX000601.; Research reported in this publication was also supported by the SAMRC under a Self-Initiated Research Grant.; MSB is funded by the Autism Science Foundation (Grant No. 17-001) and the Seaver Autism Center for Research and Treatment.; The contents do not represent the views of the Department of Veterans Affairs or the United States Government.; Further, the views and opinions expressed are those of the authors and do not necessarily represent the official views of the SAMRC.; HJZ is supported by a SAMRC Unit on Child and Adolescent Health, University of Cape Town, South Africa.; The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: ANIMAL-MODELS; PRETERM INFANTS; Psychiatry; SCHIZOPHRENIA; Science & Technology; Neurosciences & Neurology; AUTISM SPECTRUM DISORDER; BECK DEPRESSION INVENTORY; Immunology; POSTTRAUMATIC-STRESS-DISORDER; Schizophrenia; Life Sciences & Biomedicine; SEROTONERGIC NEURONAL PHENOTYPE; INVOLVEMENT SCREENING-TEST; PTSD; Autism spectrum disorder; Trauma; Depression; BRAIN-DEVELOPMENT; The Drakenstein Child Health Study; IMMUNE ACTIVATION; Stress response; Neurosciences
• Research Categories: Health Sciences, Mental Health; Biology, Genetics

Abstract

Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n = 20), depression (n = 31) and PTSD with comorbid depression (n = 13), compared to carefully matched trauma exposed controls (n = 23) and healthy mothers (n = 62). Analyses by maternal diagnoses revealed a clear pattern of gene expression signatures distinguishing neonates born to mothers with a history of psychopathology from those without. Co-expression network analysis identified distinct gene expression perturbations across maternal diagnoses, including two depression-related modules implicated in axon-guidance and mRNA stability, as well as two PTSD-related modules implicated in TNF signaling and cellular response to stress. Notably, these disease-related modules were enriched with brain-expressed genes and genetic risk loci for autism spectrum disorder and schizophrenia, which may imply a causal role for impaired developmental outcomes. These molecular alterations preceded changes in clinical measures at twenty-four months, including reductions in cognitive and socio-emotional outcomes in affected infants. Collectively, these findings indicate that prenatal exposure to maternal psychological distress induces neuronal, immunological and behavioral abnormalities in affected offspring and support the search for early biomarkers of exposures to adverse in utero environments and the classification of children at risk for impaired development.