title: Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain.
abstract: 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.
authors.affiliation: Neuroendocrinology Bakker Group, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands. Electronic address: e.hoekzema@nin.knaw.nl.
authors.forename: Elseline
authors.initials: E
authors.lastname: Hoekzema
authors.affiliation: Department of Pediatric Endocrinology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Department of Pediatrics, Leiden University Medical Center, Leiden The Netherlands.
authors.forename: Sebastian E E
authors.initials: SE
authors.lastname: Schagen
authors.affiliation: Center of Expertise on Gender Dysphoria, Department of Medical Psychology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Baudewijntje P C
authors.initials: BP
authors.lastname: Kreukels
authors.affiliation: Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Center of Expertise on Gender Dysphoria, Department of Medical Psychology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Peggy T
authors.initials: PT
authors.lastname: Cohen-Kettenis
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden The Netherlands.
authors.forename: Henriette
authors.initials: H
authors.lastname: Delemarre-van de Waal
authors.affiliation: Neuroendocrinology Bakker Group, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands; Centre Interdisciplinaire de Géneoprotéomique Appliquée, Université Liège, Liège, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Bakker
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology*; D005260:Female; D000068116:Gender Dysphoria / Q000473:pathology*; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D010363:Pattern Recognition, Automated; D012727:Sex Characteristics; D014189:Transsexualism / Q000473:pathology*
keywords: Gender identity disorder; MRI; Sex differences; Transsexual; Transsexualism; Voxel-based morphometry