The present study explores the interplay between maternal prenatal depressive symptoms and cortisol levels in predicting infant brain development, with a focus on neonatal corpus callosum (CC) integrity. Leveraging data from the FinnBrain Birth Cohort Study, we involved 40 mother-infants dyads. We conducted DTI imaging on 2-5-week-old infants to estimate fractional anisotropy (FA) values in CC regions (Genu, Body, and Splenium) and evaluated maternal prenatal cortisol levels through hair cortisol concentration (HCC). The latter reflects cortisol concentration over the last five months of pregnancy. To create a comprehensive measure of maternal depressive symptoms during pregnancy, a factor score was computed from EPDS questionnaire data gathered at gestational weeks 14, 24, 34. We used multivariate regression models adopting a Bayesian approach for statistical testing and controlled our models for several maternal, infant and hair sample related attributes. Results revealed that infants exposed to both prenatal maternal depressive symptoms (i.e., EPDS score above the mean) and higher HCC showed lower FA in all the CC regions considered [BGenu= -0.003, 90% HPDI (-0.005, -0.001); BBody= -0.003, 90% HPDI (-0.006, -0.001); BSplenium= -0.004, 90% HPDI (-0.008, -0.001)] (Figure1). The 90% Credible Intervals of the explained variance (R2) for each CC variable were 0.21-0.54 for Genu, 0.18-0.51 for Body, 0.15-0.49 for Splenium. Present findings underscore the intricate dynamics between maternal prenatal cortisol levels and depressive symptoms, revealing a nuanced influence on the structural integrity of infants' CC.Figure1. Infants' FA as a function of the interaction between maternal EPDS (mean ± standard deviation) and HCC (ln(pg/mg)).