PT  - JOURNAL ARTICLE
AU  - Michael S. Breen
AU  - Aliza P. Wingo
AU  - Nastassja Koen
AU  - Kirsten A. Donald
AU  - Heather J. Zar
AU  - Kerry J. Ressler
AU  - Joseph D. Buxbaum
AU  - Dan J. Stein
TI  - Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes
AID  - 10.1101/216309
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 216309
4099  - http://biorxiv.org/content/early/2017/11/08/216309.short
4100  - http://biorxiv.org/content/early/2017/11/08/216309.full
AB  - 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 measures as well as adaptive behaviours 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 as well as the classification of children at risk for impaired neurodevelopment.