Antenatal depression and offspring neurodevelopment Exploring underlying pathways and a psychological intervention

Depression during pregnancy is a relatively common condition. Children born from these pregnancies are at risk for a wide range of neurodevelopmental disorders. This increased risk cannot be explained fully by genetic inheritance or postnatal influences, suggesting a direct effect of depression during pregnancy on fetal neurodevelopment. The underlying biological mechanisms that may drive the described associations between prenatal exposure to maternal depression and child neurodevelopmental deficits, are largely unknown. In this thesis, we aimed to gain more insight into these mechanisms. Our first aim was to examine if depression during pregnancy affects the stress system in women and their children. Our second aim was to explore whether Cognitive Behavioural Therapy (CBT) in pregnant women with depression in a pilot Randomized Controlled Trial ameliorates child neurodevelopmental outcome, including DNA methylation profiles, brain morphometry and connectivity and behaviour and cognition. In our study, self-perceived psychosocial stress did not contribute significantly to the variation in cortisol levels in pregnancy, whereas lifestyle and biological factors did. We also could not identify a clear independent association between prenatal exposure to maternal depressive symptoms and stress reactivity in the child, based on a systematic review and critical appraisal of studies. Nevertheless, we found preliminary evidence that CBT for antenatal depression may affect neurobiological outcomes in children, defined by decreased DNA methylation of genes involved in stress regulation and morphological brain changes in cortical areas associated with cognition and white matter tracts involved in the stress response. However, we could not establish any clinical beneficial effects.