Grey and white matter volumes either in treatment-naïve or hormone-treated transgender women: a voxel-based morphometry study

Many previous magnetic resonance imaging (MRI) studies have documented sex differences in brain morphology, but the patterns of sexual brain differences in transgender women – male sex assigned at birth – with a diagnosis of gender dysphoria (TW) have been rarely investigated to date. We acquired T1-weighted MRI data for the following four (n = 80) groups: treatment-naïve TW (TNTW), TW treated with cross-sex hormones for at least one year (TTW), cisgender men, and cisgender women (cisgender individuals as controls). Differences in whole-brain and regional white matter volume and grey matter volume (GMV) were assessed using voxel-based morphometry. We found lower global brain volumes and regional GMVs in a large portion of the posterior-superior frontal cortex in the cisgender women group than in the TTW and cisgender men groups. Additionally, both transgender groups exhibited lower bilateral insular GMVs than the cisgender women group. Our results highlight differences in the insula in both transgender groups; such differences may be characteristic of TW. Furthermore, these alterations in the insula could be related to the neural network of body perception and reflect the distress that accompanies gender dysphoria.

[1]  J M Tanner,et al.  Variations in the Pattern of Pubertal Changes in Boys , 1970, Archives of disease in childhood.

[2]  Rupert Lanzenberger,et al.  Subcortical gray matter changes in transgender subjects after long-term cross-sex hormone administration , 2016, Psychoneuroendocrinology.

[3]  Margaret M McCarthy,et al.  Reframing sexual differentiation of the brain , 2011, Nature Neuroscience.

[4]  Catherine Lord,et al.  Effect of sex and estrogen therapy on the aging brain: a voxel-based morphometry study , 2010, Menopause.

[5]  B. Mendonca,et al.  Clinical management of transsexual subjects. , 2014, Arquivos brasileiros de endocrinologia e metabologia.

[6]  Gereon R Fink,et al.  Sex differences and the impact of steroid hormones on the developing human brain. , 2009, Cerebral cortex.

[7]  Luke J. Chang,et al.  Decoding the role of the insula in human cognition: functional parcellation and large-scale reverse inference. , 2013, Cerebral cortex.

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

[9]  Esther Gómez-Gil,et al.  Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals. , 2014, The journal of sexual medicine.

[10]  Sandra F. Witelson,et al.  Neural sexual mosaicism: Sexual differentiation of the human temporo-parietal region for functional asymmetry , 1991, Psychoneuroendocrinology.

[11]  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.

[12]  Christina J. Herold,et al.  Comparison of grey matter volume and thickness for analysing cortical changes in chronic schizophrenia: A matter of surface area, grey/white matter intensity contrast, and curvature , 2015, Psychiatry Research: Neuroimaging.

[13]  R. Gorski,et al.  Sex differences in the corpus callosum of the living human being , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  Dick J. Veltman,et al.  Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain , 2015, Psychoneuroendocrinology.

[15]  Cheng-Ta Li,et al.  Brain Signature Characterizing the Body-Brain-Mind Axis of Transsexuals , 2013, PloS one.

[16]  Dorret I. Boomsma,et al.  Sex steroids and brain structure in pubertal boys and girls , 2009, Psychoneuroendocrinology.

[17]  John Suckling,et al.  Biological sex affects the neurobiology of autism , 2013, Brain : a journal of neurology.

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

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

[20]  Marina Boccardi,et al.  Effects of hormone therapy on brain morphology of healthy postmenopausal women: a Voxel-based morphometry study , 2006, Menopause.

[21]  A. Craig,et al.  How do you feel — now? The anterior insula and human awareness , 2009, Nature Reviews Neuroscience.

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

[23]  G. Castellini,et al.  Cross-sex hormonal treatment and body uneasiness in individuals with gender dysphoria. , 2014, The journal of sexual medicine.

[24]  Sébastien Ourselin,et al.  Head size, age and gender adjustment in MRI studies: a necessary nuisance? , 2010, NeuroImage.

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

[26]  Karl J. Friston,et al.  Cerebral Asymmetry and the Effects of Sex and Handedness on Brain Structure: A Voxel-Based Morphometric Analysis of 465 Normal Adult Human Brains , 2001, NeuroImage.

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

[28]  Rupert Lanzenberger,et al.  White Matter Microstructure in Transsexuals and Controls Investigated by Diffusion Tensor Imaging , 2014, The Journal of Neuroscience.

[29]  Daniel S. Margulies,et al.  Sex beyond the genitalia: The human brain mosaic , 2015, Proceedings of the National Academy of Sciences.

[30]  Randy L. Gollub,et al.  Reproducibility of quantitative tractography methods applied to cerebral white matter , 2007, NeuroImage.

[31]  Rupert Lanzenberger,et al.  Structural Connectivity Networks of Transgender People , 2014, Cerebral cortex.

[32]  S. Baron-Cohen,et al.  Neuroscience and Biobehavioral Reviews a Meta-analysis of Sex Differences in Human Brain Structure , 2022 .

[33]  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.

[34]  O. Blanke,et al.  Distinct illusory own-body perceptions caused by damage to posterior insula and extrastriate cortex. , 2013, Brain : a journal of neurology.

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

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

[37]  L. Cahill.  Why sex matters for neuroscience , 2006, Nature Reviews Neuroscience.

[38]  Jesús Pujol,et al.  Cross-Sectional and Longitudinal Assessment of Structural Brain Alterations in Melancholic Depression , 2011, Biological Psychiatry.

[39]  Nikolaus Weiskopf,et al.  A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging , 2009, NeuroImage.

[40]  R. Woods,et al.  Sex differences in cortical thickness mapped in 176 healthy individuals between 7 and 87 years of age. , 2007, Cerebral cortex.

[41]  Siegfried Kasper,et al.  Regional sex differences in grey matter volume are associated with sex hormones in the young adult human brain , 2010, NeuroImage.

[42]  C. Aring,et al.  A CRITICAL REVIEW , 1939, Journal of neurology and psychiatry.

[43]  C. Winslow,et al.  Sexual Behavior in the Human Male , 1948 .

[44]  A. Manzouri,et al.  Anatomical and Functional Findings in Female‐to‐Male Transsexuals: Testing a New Hypothesis , 2015, Cerebral cortex.

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

[46]  Chou-Ming Cheng,et al.  Neural Network of Body Representation Differs between Transsexuals and Cissexuals , 2014, PloS one.

[47]  M. Hines,et al.  Gender Assignment, Reassignment and Outcome in Disorders of Sex Development: Update of the 2005 Consensus Conference , 2016, Hormone Research in Paediatrics.

[48]  P. Szeszko,et al.  MRI atlas of human white matter , 2006 .

[49]  Stefan Klöppel,et al.  Homosexual Women Have Less Grey Matter in Perirhinal Cortex than Heterosexual Women , 2007, PloS one.

[50]  Zsolt Unoka,et al.  Regional Grey Matter Structure Differences between Transsexuals and Healthy Controls—A Voxel Based Morphometry Study , 2013, PloS one.

[51]  Meng Li,et al.  Gender consistency and difference in healthy adults revealed by cortical thickness , 2010, NeuroImage.

[52]  Peter A. Calabresi,et al.  Tract probability maps in stereotaxic spaces: Analyses of white matter anatomy and tract-specific quantification , 2008, NeuroImage.

[53]  C. Junqué,et al.  A Review of the Status of Brain Structure Research in Transsexualism , 2016, Archives of Sexual Behavior.

[54]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

[55]  G. Busatto.  Structural and functional neuroimaging studies in major depressive disorder with psychotic features: a critical review. , 2013, Schizophrenia bulletin.

[56]  Clyde E. Martin,et al.  Sexual behavior in the human male. 1948. , 2003, American journal of public health.

[57]  N. Makris,et al.  Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. , 2001, Cerebral cortex.

[58]  Hilleke E. Hulshoff Pol,et al.  Changing your sex changes your brain: influences of testosterone and estrogen on adult human brain structure , 2006 .

[59]  A. Simmons,et al.  Effects of estrogen therapy on age-related differences in gray matter concentration , 2009, Climacteric : the journal of the International Menopause Society.

[60]  Karl J. Friston,et al.  Unified segmentation , 2005, NeuroImage.

[61]  M. Lipton,et al.  Estrogen- and progesterone-mediated structural neuroplasticity in women: evidence from neuroimaging , 2016, Brain Structure and Function.