Sexually divergent development of depression-related brain networks during healthy human adolescence

We hypothesized that there are sexual differences in human brain network development underlying the female > male divergence in adolescent depression. We tested for sex differences in parameters of brain network development (accelerated longitudinal fMRI, N=298 healthy adolescents, each scanned 1 to 3 times). Sexually divergent development of functional connectivity was located in default mode network (DMN), limbic cortex, and subcortical nuclei. Females had a more "disruptive" pattern of development, where weak functional connectivity at age 14 became stronger during adolescence. This fMRI-derived map of divergent adolescent development was co-located with (i) a map of functional dysconnectivity associated with adult major depressive disorder (MDD); and (ii) an adult brain gene expression pattern enriched for genes on the X chromosome, neurodevelopmental genes, and risk genes for MDD. Sexual divergence in disruptive development of DMN, limbic and subcortical functional networks is potentially relevant to the increased risk of depression in adolescent females.