Perinatal Maternal Depressive Symptoms and Brain Connectivity Among 9- to 15-Year-Old Offspring

Importance Maternal depressive symptoms during the perinatal period have been associated with offspring neurodevelopment. However, the longitudinal association of prenatal and postnatal maternal depressive symptoms with the developmental change in functional brain networks among offspring remains unclear. Objective To examine the associations of prenatal and postnatal maternal depressive symptoms with offspring functional brain connectivity development from midchildhood to adolescence. Design, Setting, and Participants This single-site, population-based prospective cohort was embedded in the Generation R Study, conducted in Rotterdam, the Netherlands. All pregnant individuals with an expected delivery date between April 1, 2002, and January 31, 2006, were invited to participate. The study included 2825 mother-child dyads with 3627 resting-state functional magnetic resonance imaging (fMRI) scans. Participants were eligible if they had valid resting-state fMRI data from at least 1 of the 2 waves of neuroimaging. Maternal depressive symptoms were assessed during pregnancy and in the early postnatal period. Offspring underwent 2 neuroimaging assessments at age 9 to 15 years. Data were analyzed from February to December 2024. Exposure Maternal depressive symptoms were assessed using the Brief Symptom Inventory during midpregnancy and at 2 and 6 months post partum. Depressive symptom levels were analyzed both continuously and as clinically relevant dichotomized categories. Main Outcomes and Measures The primary outcomes were brainwide graph theory metrics, including integration (global efficiency) and segregation (modularity, clustering coefficient) derived from resting-state functional connectivity (RSFC). Secondary outcomes included within-RSFC and between-RSFC networks, defined by the Gordon parcellation. Results The study included 2825 mother-child dyads (mean [SD] maternal age at intake, 31.1 [4.7] years; 1496 female children [53.0%]). Prenatal depressive symptoms were associated with greater increases in global efficiency (β = 0.004, SE = 0.000; false discovery rate [FDR]–corrected P = .002), modularity (β = 0.003, SE = 0.000; FDR-corrected P = .002), and within-network default mode network connectivity (β = 0.010, SE = 0.001; FDR-corrected P = .002) from midchildhood to adolescence. Postnatal depressive symptoms showed no significant association with offspring functional connectivity measures. Baseline internalizing problems were associated with greater increases in global efficiency among children exposed to clinically relevant prenatal depressive symptoms (β = 0.243, SE = 0.37; FDR-corrected P = .001). Conclusions and Relevance In this population-based cohort study of 9- to-15-year-old children, prenatal maternal depressive symptoms were associated with differences in the trajectories of functional brain connectivity. These findings highlight the relevance of prenatal maternal mental health in understanding offspring neurodevelopmental processes.