title: Role of testosterone and Y chromosome genes for the masculinization of the human brain.
abstract: Women with complete androgen insensitivity syndrome (CAIS) have a male (46,XY) karyotype but no functional androgen receptors. Their condition, therefore, offers a unique model for studying testosterone effects on cerebral sex dimorphism. We present MRI data from 16 women with CAIS and 32 male (46,XY) and 32 female (46,XX) controls.
  
  
  
  FreeSurfer software was employed to measure cortical thickness and subcortical structural volumes. Axonal connections, indexed by fractional anisotropy, (FA) were measured with diffusion tensor imaging, and functional connectivity with resting state fMRI.
  
  
  
  Compared to men, CAIS women displayed a "female" pattern by having thicker parietal and occipital cortices, lower FA values in the right corticospinal, superior and inferior longitudinal tracts, and corpus callosum. Their functional connectivity from the amygdala to the medial prefrontal cortex, was stronger and amygdala-connections to the motor cortex weaker than in control men. CAIS and control women also showed stronger posterior cingulate and precuneus connections in the default mode network. Thickness of the motor cortex, the caudate volume, and the FA in the callosal body followed, however, a "male" pattern.
  
  
  
  Altogether, these data suggest that testosterone modulates the microstructure of somatosensory and visual cortices and their axonal connections to the frontal cortex. Testosterone also influenced functional connections from the amygdala, whereas the motor cortex could, in agreement with our previous reports, be moderated by processes linked to X-chromosome gene dosage. These data raise the question about other genetic factors masculinizing the human brain than the SRY gene and testosterone. Hum Brain Mapp 38:1801-1814, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, SE-113 30, Sweden.|Department of Neurology, Stockholm, SE-113 30, Sweden.
authors.forename: Ivanka
authors.initials: I
authors.lastname: Savic
authors.affiliation: Dept of Clinical Neuroscience, Stockholm, SE-113 30, Sweden.|Child and Adolescent Psychiatry Research Center, Stockholm, SE-113 30, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Frisen
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, SE-113 30, Sweden.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Manzouri
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, SE-113 30, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Nordenstrom
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, SE-113 30, Sweden.|Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Angelica
authors.initials: A
authors.lastname: Lindén Hirschberg
mesh_terms: D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D005260:Female; D005385:Fingers / Q000473:pathology; D050173:Genes, Y-Linked / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D012727:Sex Characteristics; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000378:metabolism*; D055815:Young Adult
chemical_list: D013739:Testosterone
keywords: MRI; Y-chromosome; disorders of sexual differentiation; gender