Sex versus Gender Role Endorsement Associations With White Matter Microstructure in South African Adults: A Diffusion Tensor Imaging Study

BACKGROUND: Brain structure in transgender individuals is often shifted away from their natal sex toward their preferred gender identity. However, little is known about the relationship between gender identity and white matter microstructure in the general population. METHODS: We investigated the associations of biological sex versus gender role endorsement with white matter microstructure in healthy South African adults (n = 88; 46 males, 42 females) meticulously screened for mental illness, medical comorbidities, intracranial pathologies, significant head trauma, and substance use. Gender role endorsement was assessed as a dimensional measure across a continuum using the Bem Sex Role Inventory. Diffusion tensor imaging was used to calculate fractional anisotropy (FA) for selected fronto-limbic white matter tracts of interest. RESULTS: We observed a significant interaction effect between biological sex and gender role endorsement across multiple white matter tracts, including the trunk of the corpus callosum, left corticospinal tract, left superior longitudinal fasciculus, right cingulum bundle, right inferior fronto-occipital fasciculus, and left uncinate fasciculus. Post-hoc tests revealed that higher feminine gender role endorsement was associated with lower FA in these tracts among males, but not females. CONCLUSIONS: Gender nonconformity in males is linked to a "sex-reversed" pattern of white matter microstructure in healthy adults recruited from a general population setting. Future longitudinal studies are needed to investigate how sex, gender identity, genetics, sex hormones, and environmental exposures interact to shape white matter development across the lifespan.