Prenatal Selective Serotonin Reuptake Inhibitor Exposure, Depression and Brain Morphology in Middle Childhood: Results from the ABCD Study

ABSTRACT Objective Prenatal selective serotonin reuptake inhibitor (SSRI) exposure has been inconsistently linked to depression. Potential neural intermediaries remain understudied. We examined whether prenatal SSRI exposure is associated with depressive symptoms and brain structure during middle childhood. Methods Prenatal SSRI exposure (retrospective caregiver-report), depressive symptoms (caregiver-reported Child Behavior Checklist) and brain structure (MRI-derived subcortical volume; cortical thickness and surface area) were assessed in children (analytic ns=5,420-7,528; 235 with prenatal SSRI exposure; 9-10 years old) who completed the baseline session of the Adolescent Brain and Cognitive Development SM Study. Covariates included familial (e.g., 1 st degree relative depression density), pregnancy (e.g., planned pregnancy), and child (e.g., birthweight) variables. Matrix spectral decomposition was used to address multiple testing. Results There was no evidence that prenatal SSRI exposure was associated with child depression after accounting for recent maternal depressive symptoms. Prenatal SSRI exposure was associated with greater left superior parietal surface area (b=145.3 mm 2 , p=0.00038) and lateral occipital cortical thickness (b=0.0272 mm, p=0.0000079), neither of which was associated with depressive symptoms. Conclusions Our findings, combined with adverse associations of prenatal exposure to maternal depression and the utility of SSRIs for treating depression, suggest that risk for child depression during middle childhood should not discourage SSRI use during pregnancy. It will be important for future work to examine associations between prenatal SSRI exposure and depression through young adulthood, when risk for depression increases.