Exploring epigenetic and neural mechanisms underlying development in children born during the COVID-19 pandemic

Exposure to prenatal depression and anxiety increases the risk of developmental delays, internalizing and externalizing problems, in early childhood and later neurodevelopmental, mood and anxiety disorders. Rates of prenatal anxiety and depression significantly increased during the COVID-19 pandemic, which our team has shown can impact brain connectivity during infancy. However, the underlying mechanisms linking prenatal adversity to poor child development remain unclear. The proposed project will elucidate potential neurobiological and epigenetic pathways in the intergenerational transmission of psychopathology, across two aims: 1) Determine if DNA methylation in oxytocin related genes (e.g., OXT, OXTR, AVP, AVPR) represents a mechanism linking exposure to prenatal distress during the pandemic with poorer brain connectivity in areas known to be rich in oxytocin and implicated in emotion regulation (e.g., the amygdala and medial prefrontal cortex) during early childhood; 2) Determine if brain connectivity represents a mechanism linking exposure to prenatal distress during the pandemic with risk for psychopathology as measured by poorer performance on cognitive functioning tasks and parent-reported developmental outcomes. To do this we will conduct a neuroimaging sub-study within the larger established Pregnancy during the COVID-19 Pandemic (PdP) cohort. Self-reported measures of distress were previously collected during pregnancy. For this project, we will invite participants to bring their 3-5-year-old children (n=155) to the new Imagine Centre at the CHU Sainte Justine children's hospital in Montreal, Quebec. We will conduct MRI scanning on a state-of-the-art Siemens Cima.X 3T to assess structural and functional brain connectivity, collect a saliva sample for DNA and methylation analysis, complete cognitive functioning tasks, and administer a validated parent-report questionnaire of child functioning. Findings will improve our understanding of the mechanisms underlying the intergenerational transmission of psychopathology, and in turn have the potential to inform targeted intervention approaches by providing novel biomarkers for early identification of children at risk.