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See detailRegional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain.
Hoekzema, Elseline; Schagen, Sebastian E. E.; Kreukels, Baudewijntje P. C. et al

in Psychoneuroendocrinology (2015), 55C

The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine ... [more ▼]

The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural gray matter (GM) volumes in 55 female-to-male and 38 male-to-female adolescents, 44 boys and 52 girls without GD and applied both univariate and multivariate analyses. In girls, more GM volume was observed in the left superior medial frontal cortex, while boys had more volume in the bilateral superior posterior hemispheres of the cerebellum and the hypothalamus. Regarding the GD groups, at whole-brain level they differed only from individuals sharing their gender identity but not from their natal sex. Accordingly, using multivariate pattern recognition analyses, the GD groups could more accurately be automatically discriminated from individuals sharing their gender identity than those sharing their natal sex based on spatially distributed GM patterns. However, region of interest analyses indicated less GM volume in the right cerebellum and more volume in the medial frontal cortex in female-to-males in comparison to girls without GD, while male-to-females had less volume in the bilateral cerebellum and hypothalamus than natal boys. Deviations from the natal sex within sexually dimorphic structures were also observed in the untreated subsamples. Our findings thus indicate that GM distribution and regional volumes in GD adolescents are largely in accordance with their respective natal sex. However, there are subtle deviations from the natal sex in sexually dimorphic structures, which can represent signs of a partial sex-atypical differentiation of the brain. [less ▲]

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See detailNeural Activation During Mental Rotation in Complete Androgen Insensitivity Syndrome: the Influence of Sex Hormones and Sex Chromosomes.
van Hemmen, Judy; Veltman, Dick J.; Hoekzema, Elseline et al

in Cerebral Cortex (2014)

Sex hormones, androgens in particular, are hypothesized to play a key role in the sexual differentiation of the human brain. However, possible direct effects of the sex chromosomes, that is, XX or XY ... [more ▼]

Sex hormones, androgens in particular, are hypothesized to play a key role in the sexual differentiation of the human brain. However, possible direct effects of the sex chromosomes, that is, XX or XY, have not been well studied in humans. Individuals with complete androgen insensitivity syndrome (CAIS), who have a 46,XY karyotype but a female phenotype due to a complete androgen resistance, enable us to study the separate effects of gonadal hormones versus sex chromosomes on neural sex differences. Therefore, in the present study, we compared 46,XY men (n = 30) and 46,XX women (n = 29) to 46,XY individuals with CAIS (n = 21) on a mental rotation task using functional magnetic resonance imaging. Previously reported sex differences in neural activation during mental rotation were replicated in the control groups, with control men showing more activation in the inferior parietal lobe than control women. Individuals with CAIS showed a female-like neural activation pattern in the parietal lobe, indicating feminization of the brain in CAIS. Furthermore, this first neuroimaging study in individuals with CAIS provides evidence that sex differences in regional brain function during mental rotation are most likely not directly driven by genetic sex, but rather reflect gonadal hormone exposure. [less ▲]

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