Sex differences in human deep grey matter microstructure emerge during adolescence

Many neuropsychiatric disorders demonstrate sex-based differences in their prevalence, onset age, and phenotypic presentation. The neuroanatomic and neurophysiologic substrates that underpin these sex differences are not fully understood. Animal studies have demonstrated sex differences in neuronal, dendritic, and glial microstructure. Restriction Spectrum Imaging (RSI) is an advanced diffusion MR technique that delineates the intracellular, extracellular, and free water contributions to diffusion signal, providing unique insights into microstructure. A recent RSI study showed large sex differences in subcortical gray matter structures in young adults, most significantly in the hippocampus, amygdala, and nucleus accumbens, which persist when controlling for age and volume. In this study, we use RSI to examine sex-related cross-sectional developmental patterns in subcortical gray matter across childhood and adolescence into early adulthood by combining the Human Connectome Project-Development and Young Adult datasets (ages 9-35 years). We observe that sex differences emerge over adolescence, with males showing higher restricted diffusion and lower hindered diffusion than females across all deep gray structures interrogated. We establish sex-stratified MR diffusion based normative age curves, for subcortical gray matter that will support future neurodevelopmental research.