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

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 analyzed transcriptome-wide gene expression profiles of 149 UCB samples from neonates born to mothers with prenatal PTSD (n=20), depression (n=31) and PTSD with comorbid depression (PTSD/Dep; n=13), compared to neonates born to carefully matched trauma exposed controls without meeting PTSD criteria (TE; n=23) and healthy mothers (n=62). We also evaluated physiological and developmental measures in these infants at birth, six months and twenty-four months. A multistep analytic approach was used that specifically sought to: 1) identify dysregulated genes, molecular pathways and discrete groups of co-regulated gene modules in UCB associated with prenatal maternal psychopathologies; and 2) to determine the impact of perinatal PTSD and depression on early childhood development outcomes. Transcriptome-wide gene expression assays were applied to 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).