Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes
Year: 2018
Type: article
Study design: Observational Study
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.
Source: Brain Behavior and Immunity
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,842
Funders: U.S. Department of Veterans Affairs, Bill and Melinda Gates Foundation, Autism Science Foundation, Academy of Medical Sciences, National Research Foundation, South African Medical Research Council, University of Cape Town, National Institutes of Health, Medical Research Council, National Institute on Aging, National Institute of Mental Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1139794871, Understanding the molecular mechanisms of Depression and Psychological Well-being in Alzheimer's disease, G313943611, G3685900323, G5322685125, Understanding the transgenerational epigenetic effect of maternal psychosocial trauma exposure on infants via lncRNA-sequencing, G7645630759, Transgenerational Effects of Maternal Stressors: Investigating the Role of Infant Gene Expression, G935971202
OpenAlex ID: W2951989290