White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study.

BACKGROUND Some gray and white matter regions of the brain are sexually dimorphic. The best MRI technique for identifying subtle differences in white matter is diffusion tensor imaging (DTI). The purpose of this paper is to investigate whether white matter patterns in female to male (FtM) transsexuals before commencing cross-sex hormone treatment are more similar to that of their biological sex or to that of their gender identity. METHOD DTI was performed in 18 FtM transsexuals and 24 male and 19 female heterosexual controls scanned with a 3 T Trio Tim Magneton. Fractional anisotropy (FA) was performed on white matter fibers of the whole brain, which was spatially analyzed using Tract-Based Spatial Statistics. RESULTS In controls, males have significantly higher FA values than females in the medial and posterior parts of the right superior longitudinal fasciculus (SLF), the forceps minor, and the corticospinal tract. Compared to control females, FtM showed higher FA values in posterior part of the right SLF, the forceps minor and corticospinal tract. Compared to control males, FtM showed only lower FA values in the corticospinal tract. CONCLUSIONS Our results show that the white matter microstructure pattern in untreated FtM transsexuals is closer to the pattern of subjects who share their gender identity (males) than those who share their biological sex (females). Our results provide evidence for an inherent difference in the brain structure of FtM transsexuals.

[1]  D. Swaab Sexual differentiation of the human brain: relevance for gender identity, transsexualism and sexual orientation , 2004, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[2]  N. F. Ramsey,et al.  Effects of cross-sex hormones on cerebral activation during language and mental rotation: An fMRI study in transsexuals , 2008, European Neuropsychopharmacology.

[3]  M. Domingo,et al.  [Estimation of prevalence, incidence and sex ratio of transsexualism in Catalonia according to health care demand]. , 2006 .

[4]  M. Salamero,et al.  Sociodemographic, Clinical, and Psychiatric Characteristics of Transsexuals from Spain , 2009, Archives of sexual behavior.

[5]  C. Junqué,et al.  Cortical activation during mental rotation in male-to-female and female-to-male transsexuals under hormonal treatment , 2010, Psychoneuroendocrinology.

[6]  W. Heindel,et al.  The functional anatomy of semantic retrieval is influenced by gender, menstrual cycle, and sex hormones , 2008, Journal of Neural Transmission.

[7]  E. Melhem,et al.  Diffusion-tensor MR imaging and tractography: exploring brain microstructure and connectivity. , 2007, Radiology.

[8]  E. Rolls,et al.  The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology , 2004, Progress in Neurobiology.

[9]  C. Junqué,et al.  Sex differences in the human olfactory system , 2006, Brain Research.

[10]  E. Amparo,et al.  Anatomic variation of the corpus callosum in persons with gender dysphoria , 1991, Archives of sexual behavior.

[11]  M. Salamero,et al.  Androgen treatment effects on memory in female-to-male transsexuals , 2009, Psychoneuroendocrinology.

[12]  Daniel Rueckert,et al.  Nonrigid registration using free-form deformations: application to breast MR images , 1999, IEEE Transactions on Medical Imaging.

[13]  Charles Watson,et al.  Spinal Cord: Connections , 2012 .

[14]  Richard A. Lippa,et al.  Sex Differences in Mental Rotation and Line Angle Judgments Are Positively Associated with Gender Equality and Economic Development Across 53 Nations , 2010, Archives of sexual behavior.

[15]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[16]  Isabel Wanke,et al.  Gender-specific cerebral activation during cognitive tasks using functional MRI: comparison of women in mid-luteal phase and men , 2005, Neuroradiology.

[17]  Vincent J Schmithorst,et al.  Developmental differences in white matter architecture between boys and girls , 2008, Human brain mapping.

[18]  J. Rothwell,et al.  Mapping genetic influences on the corticospinal motor system in humans , 2009, Neuroscience.

[19]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[20]  René Westerhausen,et al.  The influence of handedness and gender on the microstructure of the human corpus callosum: a diffusion-tensor magnetic resonance imaging study , 2003, Neuroscience Letters.

[21]  S. Segovia,et al.  Sexual dimorphism in the vomeronasal pathway and sex differences in reproductive behaviors , 1993, Brain Research Reviews.

[22]  Dick F. Swaab,et al.  A sex difference in the human brain and its relation to transsexuality , 1995, Nature.

[23]  D F Swaab,et al.  Male-to-female transsexuals have female neuron numbers in a limbic nucleus. , 2000, The Journal of clinical endocrinology and metabolism.

[24]  M. Jenkinson,et al.  Non-linear optimisation FMRIB Technial Report TR 07 JA 1 , 2007 .

[25]  A. Simmons,et al.  Comparable fMRI activity with differential behavioural performance on mental rotation and overt verbal fluency tasks in healthy men and women , 2006, Experimental Brain Research.

[26]  Dong Ik Kim,et al.  Corpus callosal connection mapping using cortical gray matter parcellation and DT‐MRI , 2008, Human brain mapping.

[27]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[28]  D. Kimura Sex and cognition , 1999 .

[29]  Alexander Leemans,et al.  Microstructural maturation of the human brain from childhood to adulthood , 2008, NeuroImage.

[30]  John H. Martin,et al.  Activity- and use-dependent plasticity of the developing corticospinal system , 2007, Neuroscience & Biobehavioral Reviews.

[31]  P. Cohen-Kettenis,et al.  Transsexualism: a review of etiology, diagnosis and treatment. , 1999, Journal of psychosomatic research.

[32]  A. Finset,et al.  Sex-sensitive cognitive performance in untreated patients with early onset gender identity disorder , 2003, Psychoneuroendocrinology.

[33]  Y. Kawamura,et al.  Callosal Shapes at the Midsagittal Plane: MRI Differences of Normal Males, Normal Females, and GID , 2005, 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference.

[34]  Alicia Garcia-Falgueras,et al.  A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. , 2008, Brain : a journal of neurology.

[35]  R. Blanchard,et al.  Heterosexual and homosexual gender dysphoria , 1987, Archives of sexual behavior.

[36]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[37]  D. Segal Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) , 2010 .

[38]  K. Hugdahl,et al.  Sex differences in visuo-spatial processing: An fMRI study of mental rotation , 2006, Neuropsychologia.

[39]  M. Ladd,et al.  Specific cerebral activation due to visual erotic stimuli in male-to-female transsexuals compared with male and female controls: an fMRI study. , 2009, The journal of sexual medicine.

[40]  Sandra Black,et al.  Corpus Callosum Anatomy in Right-Handed Homosexual and Heterosexual Men , 2008, Archives of sexual behavior.

[41]  P. Cohen-Kettenis,et al.  The Harry Benjamin International Gender Dysphoria Association's Standards of Care for Gender Identity Disorders, Sixth Version , 2002 .

[42]  G. Paxinos,et al.  THE HUMAN NERVOUS SYSTEM , 1975 .

[43]  Arthur W. Toga,et al.  Regional gray matter variation in male-to-female transsexualism , 2009, NeuroImage.

[44]  T. Wüstenberg,et al.  Women and men exhibit different cortical activation patterns during mental rotation tasks , 2002, Neuropsychologia.

[45]  Frank Kreuder,et al.  Hemispheric and gender related differences in the midcingulum bundle: A DTI study , 2009, Human brain mapping.

[46]  L. Gooren,et al.  The biology of human psychosexual differentiation , 2006, Hormones and Behavior.

[47]  S. H. Goozen,et al.  Transsexual subtypes: Clinical and theoretical significance , 2005, Psychiatry Research.

[48]  S. H. Goozen,et al.  Activating effects of cross-sex hormones on cognitive functioning: a study of short-term and long-term hormone effects in transsexuals , 1999, Psychoneuroendocrinology.

[49]  S. H. Goozen,et al.  COGNITIVE ABILITY AND CEREBRAL LATERALISATION IN TRANSSEXUALS , 1998, Psychoneuroendocrinology.

[50]  Almut Engelien,et al.  Neuroimaging differences in spatial cognition between men and male-to-female transsexuals before and during hormone therapy. , 2010, The journal of sexual medicine.

[51]  D. Pandya,et al.  Fiber Pathways of the Brain , 2006 .

[52]  M. Jenkinson Non-linear registration aka Spatial normalisation , 2007 .