Regional Grey Matter Structure Differences between Transsexuals and Healthy Controls—A Voxel Based Morphometry Study

Gender identity disorder (GID) refers to transsexual individuals who feel that their assigned biological gender is incongruent with their gender identity and this cannot be explained by any physical intersex condition. There is growing scientific interest in the last decades in studying the neuroanatomy and brain functions of transsexual individuals to better understand both the neuroanatomical features of transsexualism and the background of gender identity. So far, results are inconclusive but in general, transsexualism has been associated with a distinct neuroanatomical pattern. Studies mainly focused on male to female (MTF) transsexuals and there is scarcity of data acquired on female to male (FTM) transsexuals. Thus, our aim was to analyze structural MRI data with voxel based morphometry (VBM) obtained from both FTM and MTF transsexuals (n = 17) and compare them to the data of 18 age matched healthy control subjects (both males and females). We found differences in the regional grey matter (GM) structure of transsexual compared with control subjects, independent from their biological gender, in the cerebellum, the left angular gyrus and in the left inferior parietal lobule. Additionally, our findings showed that in several brain areas, regarding their GM volume, transsexual subjects did not differ significantly from controls sharing their gender identity but were different from those sharing their biological gender (areas in the left and right precentral gyri, the left postcentral gyrus, the left posterior cingulate, precuneus and calcarinus, the right cuneus, the right fusiform, lingual, middle and inferior occipital, and inferior temporal gyri). These results support the notion that structural brain differences exist between transsexual and healthy control subjects and that majority of these structural differences are dependent on the biological gender.

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

[2]  R. Todd Constable,et al.  Evidence That Autobiographic Memory Retrieval Does Not Become Independent of the Hippocampus: An fMRI Study Contrasting Very Recent with Remote Events , 2005, Journal of Cognitive Neuroscience.

[3]  C. Junqué,et al.  Cortical thickness in untreated transsexuals. , 2013, Cerebral cortex.

[4]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[5]  Jagath C. Rajapakse,et al.  Statistical approach to segmentation of single-channel cerebral MR images , 1997, IEEE Transactions on Medical Imaging.

[6]  L. Derogatis,et al.  The SCL-90 and the MMPI: A Step in the Validation of a New Self-Report Scale , 1976, British Journal of Psychiatry.

[7]  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.

[8]  G. Busatto,et al.  Neurostructural predictors of Alzheimer's disease: A meta-analysis of VBM studies , 2011, Neurobiology of Aging.

[9]  Jean-Luc Anton,et al.  Region of interest analysis using an SPM toolbox , 2010 .

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

[11]  Georg Northoff,et al.  Self-referential processing in our brain—A meta-analysis of imaging studies on the self , 2006, NeuroImage.

[12]  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.

[13]  C. Frith,et al.  Functional imaging of ‘theory of mind’ , 2003, Trends in Cognitive Sciences.

[14]  Karl J. Friston,et al.  Voxel-based morphometry of the human brain: Methods and applications , 2005 .

[15]  Eileen Luders,et al.  Increased Cortical Thickness in Male-to-Female Transsexualism. , 2012, Journal of behavioral and brain science.

[16]  Esther Gómez-Gil,et al.  Effects of androgenization on the white matter microstructure of female-to-male transsexuals. A diffusion tensor imaging study , 2012, Psychoneuroendocrinology.

[17]  J. Ashburner,et al.  Voxel-by-Voxel Comparison of Automatically Segmented Cerebral Gray Matter—A Rater-Independent Comparison of Structural MRI in Patients with Epilepsy , 1999, NeuroImage.

[18]  Amanda L. Kaas,et al.  Distinct cortical networks for the detection and identification of human body , 2009, NeuroImage.

[19]  Dick F. Swaab,et al.  Sexual differentiation of the human brain: Relation to gender identity, sexual orientation and neuropsychiatric disorders , 2011, Frontiers in Neuroendocrinology.

[20]  R. Blanchard,et al.  Comparison of height and weight in homosexual versus nonhomosexual male gender dysphorics , 1995, Archives of sexual behavior.

[21]  Faith M. Gunning-Dixon,et al.  Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: replicability of regional differences in volume , 2004, Neurobiology of Aging.

[22]  Esther Gómez-Gil,et al.  The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study. , 2011, Journal of psychiatric research.

[23]  Andrew E. Skodol,et al.  DSM-IV-TR Casebook: A Learning Companion to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision , 2001 .

[24]  Esther Gómez-Gil,et al.  White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. , 2011, Journal of psychiatric research.

[25]  Terry M. Peters,et al.  3D statistical neuroanatomical models from 305 MRI volumes , 1993, 1993 IEEE Conference Record Nuclear Science Symposium and Medical Imaging Conference.

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

[27]  Alan C. Evans,et al.  Fast and robust parameter estimation for statistical partial volume models in brain MRI , 2004, NeuroImage.

[28]  Nick C Fox,et al.  Pitfalls in the Use of Voxel-Based Morphometry as a Biomarker: Examples from Huntington Disease , 2010, American Journal of Neuroradiology.

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

[30]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.

[31]  R. Blanchard,et al.  The classification and labeling of nonhomosexual gender dysphorias , 1989, Archives of sexual behavior.

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

[33]  Pierrick Coupé,et al.  Author manuscript, published in "Journal of Magnetic Resonance Imaging 2010;31(1):192-203" DOI: 10.1002/jmri.22003 Adaptive Non-Local Means Denoising of MR Images with Spatially Varying Noise Levels , 2010 .

[34]  Nick C. Fox,et al.  Ten simple rules for reporting voxel-based morphometry studies , 2008, NeuroImage.

[35]  Xiaohua Chen,et al.  Sex differences in regional gray matter in healthy individuals aged 44–48 years: A voxel-based morphometric study , 2007, NeuroImage.

[36]  Ivanka Savic,et al.  Sex dimorphism of the brain in male-to-female transsexuals. , 2011, Cerebral cortex.