The concept of gender identity is uniquely human. Hence we are left with the phenomenon of men and women suffering from Gender Dysphoria (GD) also known as transsexualism to study the origins of gender identity in humans. It has been hypothesized that atypical levels of sex steroids during a perinatal critical period of neuronal sexual differentiation may be involved in the development of GD. In order to test this hypothesis, we investigated brain structure and function in individuals diagnosed with GD using magnetic resonance imaging (MRI). Since GD is often diagnosed in childhood and puberty has been proposed to be an additional organizational period in brain differentiation, we included both prepubertal children and adolescents with GD in our studies. First, we measured brain activation upon exposure to androstadienone, a putative male chemo-signal which evokes sex differences in hypothalamic activation (women > men). We found that hypothalamic responses of both adolescent girls and boys diagnosed with GD were more similar to their experienced gender than their birth sex, which supports the hypothesis of a sex-atypical brain differentiation in these individuals. At the structural level, we analyzed both regional gray matter (GM) volumes and white matter (WM) microstructure using diffusion tensor imaging. In cis-gender girls, larger GM volumes were observed in the bilateral superior medial frontal and left pre/postcentral cortex, while cis-gender boys had more volume in the bilateral superior-posterior cerebellum and hypothalamus. Within these regions of interest representing sexually dimorphic brain structures, GM volumes of both GD groups deviated from the volumetric characteristics of their birth sex towards those of individuals sharing their gender identity. Furthermore, we found intermediate patterns in WM microstructure in adolescent boys with GD, but only sex-typical ones in adolescent girls with GD. These results on brain structure are thus partially in line with a sex-atypical differentiation of the brain during early development in individuals with GD, but might also suggest that other mechanisms are involved. Indeed, using resting state MRI, we observed GD-specific functional connectivity in the visual network in adolescent girls with GD. The latter is in support of a more recent hypothesis on alterations in brain networks important for own body perception and self-referential processing in individuals with GD.
19 - 22 May 2018
European Society of Endocrinology