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.
Highlights
During prenatal development, the fetus is vulnerable to the effects of a broad range of environmental exposures, with consequences that can persist into infancy, adolescence, and adulthood
Differential module expression and prenatal maternal depression. This exploratory study applied transcriptome-wide screens to 149 umbilical cord blood (UCB) samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n = 20), depression (n = 31) and PTSD with comorbid depression (PTSD/Dep; n = 13), compared to carefully matched trauma exposed controls (TE; n = 23) and healthy mothers unexposed to trauma without depression (n = 62) (Table 1)
We observed significant reductions in social-emotional outcomes for infants exposed to prenatal trauma exposure (TE) and PTSD/Dep compared to healthy controls (P = 0.04, P = 0.04, respectively) (Fig. 4B) as well as reduced performance on adaptive behaviour subscales, including community use scores, at twenty-four months for infants exposed to prenatal PTSD/Dep compared to healthy controls (P = 0.02) (Fig. 4C). In this investigation we utilize UCB gene expression data collected from the South African Drakenstein Child Health Study to identify genes and molecular pathways associated with prenatal exposure to distinct maternal psychopathologies
Summary
The fetus is vulnerable to the effects of a broad range of environmental exposures, with consequences that can persist into infancy, adolescence, and adulthood. Maternal psychosocial distress during pregnancy, in the form of exposure to chronic stressors and depression can have profound effects on the developing fetus, and can influence behavioral and physiological outcome measures during infancy and adulthood (DiPietro, 2010; Hart and McMahon, 2006; Kinsella and Monk, 2009; Hollins, 2007). Psychiatry, Genetic and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Annenberg Building, 1470 Madison Ave. 22nd Floor, New York, NY 10129, USA (M.S. Breen).
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