title: Neural Activation During Mental Rotation in Complete Androgen Insensitivity Syndrome: The Influence of Sex Hormones and Sex Chromosomes.
abstract: 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.
authors.affiliation: Netherlands Institute for Neuroscience, Amsterdam, The Netherlands Department of Medical Psychology, Neuroscience Campus Amsterdam.
authors.forename: Judy
authors.initials: J
authors.lastname: van Hemmen
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Netherlands Institute for Neuroscience, Amsterdam, The Netherlands Department of Medical Psychology, Neuroscience Campus Amsterdam.
authors.forename: Elseline
authors.initials: E
authors.lastname: Hoekzema
authors.affiliation: Department of Medical Psychology, Neuroscience Campus Amsterdam.
authors.forename: Peggy T
authors.initials: PT
authors.lastname: Cohen-Kettenis
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus Medical Center-Sophia, Rotterdam, The Netherlands.
authors.forename: Arianne B
authors.initials: AB
authors.lastname: Dessens
authors.affiliation: Netherlands Institute for Neuroscience, Amsterdam, The Netherlands Department of Medical Psychology, Neuroscience Campus Amsterdam Group Interdisciplinaire de Genoproteomique appliquee, University of Liège, Liège, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Bakker
mesh_terms: D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D007092:Imagination / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D012399:Rotation; D012727:Sex Characteristics; D012730:Sex Chromosomes; D013028:Space Perception / Q000502:physiology*
chemical_list: D012739:Gonadal Steroid Hormones
keywords: CAIS; fMRI; sexual differentiation; spatial cognition; testosterone