Gender identity disorder; MRI; Sex differences; Transsexual; Transsexualism; Voxel-based morphometry
Abstract :
[en] The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural gray matter (GM) volumes in 55 female-to-male and 38 male-to-female adolescents, 44 boys and 52 girls without GD and applied both univariate and multivariate analyses. In girls, more GM volume was observed in the left superior medial frontal cortex, while boys had more volume in the bilateral superior posterior hemispheres of the cerebellum and the hypothalamus. Regarding the GD groups, at whole-brain level they differed only from individuals sharing their gender identity but not from their natal sex. Accordingly, using multivariate pattern recognition analyses, the GD groups could more accurately be automatically discriminated from individuals sharing their gender identity than those sharing their natal sex based on spatially distributed GM patterns. However, region of interest analyses indicated less GM volume in the right cerebellum and more volume in the medial frontal cortex in female-to-males in comparison to girls without GD, while male-to-females had less volume in the bilateral cerebellum and hypothalamus than natal boys. Deviations from the natal sex within sexually dimorphic structures were also observed in the untreated subsamples. Our findings thus indicate that GM distribution and regional volumes in GD adolescents are largely in accordance with their respective natal sex. However, there are subtle deviations from the natal sex in sexually dimorphic structures, which can represent signs of a partial sex-atypical differentiation of the brain.
Disciplines :
Neurosciences & behavior
Author, co-author :
Hoekzema, Elseline
Schagen, Sebastian E. E.
Kreukels, Baudewijntje P. C.
Veltman, Dick J.
Cohen-Kettenis, Peggy T.
Delemarre-van de Waal, Henriette
Bakker, Julie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Language :
English
Title :
Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain.
Publication date :
2015
Journal title :
Psychoneuroendocrinology
ISSN :
0306-4530
eISSN :
1873-3360
Publisher :
Elsevier, United Kingdom
Volume :
55C
Pages :
59-71
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2015 Elsevier Ltd. All rights reserved.
Achenbach T.M., Edelbrock C.S. Manual for the Child Behavior Checklist and Revised Child Behavior Profile 1983, University of Vermong, Department of Psychiatry, Burlington, VT.
Allen L.S., Hines M., Shryne J.E., Gorski R.A. Two sexually dimorphic cell groups in the human brain. J. Neurosci. 1989, 9:497-506.
American Psychiatric Association Diagnostic and Statistical Manual of Mental Health Disorders (Revised 4th ed.) 2000, Author, Washington, DC.
Arnold A.P. Sex chromosomes and brain gender. Nat.Rev Neurosci. 2004, 5:701-708.
Bakker J., Baum M.J. Role for estradiol in female-typical brain and behavioral sexual differentiation. Front. Neuroendocrinol. 2008, 29:1-16.
Bakker J., De Mees C., Douhard Q., Balthazart J., Gabant P., Szpirer J., Szpirer C. Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens. Nat. Neurosci. 2006, 9:220-226.
Bao A.M., Swaab D.F. Sexual differentiation of the human brain: relation to gender identity, sexual orientation and neuropsychiatric disorders. Front. Neuroendocrinol. 2011, 32:214-226.
Blanchard R., Clemmensen L.H., Steiner B.W. Heterosexual and homosexual gender dysphoria. Arch. Sex. Behav. 1987, 16:139-152.
Blanchard R., Dickey R., Jones C.L. Comparison of height and weight in homosexual versus nonhomosexual male gender dysphorics. Arch. Sex. Behav. 1995, 24:543-554.
Carruth L.L., Reisert I., Arnold A.P. Sex chromosome genes directly affect brain sexual differentiation. Nat. Neurosci. 2002, 5:933-934.
Chung S.C., Lee B.Y., Tack G.R., Lee S.Y., Eom J.S., Sohn J.H. Effects of age, gender, and weight on the cerebellar volume of Korean people. Brain Res. 2005, 1042:233-235.
Cohen-Kettenis P.T., Gooren L.J. Transsexualism: a review of etiology, diagnosis and treatment. J. Psychosom. Res. 1999, 46:315-333.
Coleman E., Bockting W., Botzer M., Cohen-Kettenis P., DeCuypere G., Feldman J., Fraser L., Green J., Knudson G., Meyer W.J., Monstrey S., Adler R.K., Brown G.R., Devor A.H., Meyer-Bahlburg H., Hall B.P., Pfaefflin F., Rachlin K., Robinson B., Schechter L.S., Tangpricha V., van Trotsenburg M., Vitale A., Winter S., Whittle S., Wylie K.R., Zucker K. Standards of care for the health of transsexual, transgender, and gender nonconforming people, 7th version. Int. J. Transgend. 2011, 13:165-232.
Dohler K.D., Coquelin A., Davis F., Hines M., Shryne J.E., Gorski R.A. Differentiation of the sexually dimorphic nucleus in the preoptic area of the rat brain is determined by the perinatal hormone environment. Neurosci. Lett. 1982, 33:295-298.
Dorn L.D. Measuring puberty. J. Adolesc. Health 2006, 39:625-626.
Escalona P.R., McDonald W.M., Doraiswamy P.M., Boyko O.B., Husain M.M., Figiel G.S., Laskowitz D., Ellinwood E.H., Krishnan K.R. In vivo stereological assessment of human cerebellar volume: effects of gender and age. AJNR Am. J. Neuroradiol. 1991, 12:927-929.
Filipek P.A., Richelme C., Kennedy D.N., Caviness V.S. The young adult human brain: an MRI-based morphometric analysis. Cereb. Cortex 1994, 4:344-360.
Garcia-Falgueras A., Swaab D.F. A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. Brain 2008, 131:3132-3146.
Goldstein J.M., Seidman L.J., Horton N.J., Makris N., Kennedy D.N., Caviness V.S., Faraone S.V., Tsuang M.T. Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. Cereb. Cortex 2001, 11:490-497.
Good C.D., Johnsrude I., Ashburner J., Henson R.N., Friston K.J., Frackowiak R.S. Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. NeuroImage 2001, 14:685-700.
Gorski R.A., Harlan R.E., Jacobson C.D., Shryne J.E., Southam A.M. Evidence for the existence of a sexually dimorphic nucleus in the preoptic area of the rat. J. Comp. Neurol. 1980, 193:529-539.
Hall T.C., Miller A.K.H., Corsellis J.A.N. Variations in the human Purkinje cell population according to sex and age. Neuropathol. Appl. Neurobiol. 1975, 1:267-292.
Hembree W.C., Cohen-Kettenis P., Delemarre-van de Waal H.A., Gooren L.J., Meyer W.J., Spack N.P., Tangpricha V., Montori V.M. Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 2009, 94:3132-3154.
Heylens G., De Cuypere G., Zucker K.J., Schelfaut C., Elaut E., Vanden Bossche B.H., De Baere E., T'Sjoen G. Gender identity disorder in twins: a review of the case report literature. J. Sex Med. 2012, 9:751-757.
Hines M., Ahmed S.F., Hughes I.A. Psychological outcomes and gender-related development in complete androgen insensitivity syndrome. Arch. Sex. Behav. 2003, 32:93-101.
Hulshoff Pol H.E., Cohen-Kettenis P.T., Van Haren N.E.M., Peper J.S., Brans R.G.H., Cahn W., Schnack H.G., Gooren L.J.G., Kahn R.S. Changing your sex changes your brain: influences of testosterone and estrogen on adult human brain structure. Eur. J. Endocrinol. 2006, 155:S107-S114.
Kreukels B.P., Cohen-Kettenis P.T. Puberty suppression in gender identity disorder: the Amsterdam experience. Nat. Rev. Endocrinol. 2011, 7:466-472.
Kruijver F.P., Zhou J.N., Pool C.W., Hofman M.A., Gooren L.J., Swaab D.F. Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J. Clin. Endocrinol. Metab. 2000, 85:2034-2041.
Lombardo M.V., Ashwin E., Auyeung B., Chakrabarti B., Taylor K., Hackett G., Bullmore E.T., Baron-Cohen S. Fetal testosterone influences sexually dimorphic gray matter in the human brain. J. Neurosci. 2012, 32:674-680.
Luders E., Gaser C., Narr K.L., Toga A.W. Why sex matters: brain size independent differences in gray matter distributions between men and women. J. Neurosci. 2009, 29:14265-14270.
Luders E., Narr K.L., Thompson P.M., Rex D.E., Woods R.P., Deluca H., Jancke L., Toga A.W. Gender effects on cortical thickness and the influence of scaling. Hum. Brain Mapp. 2006, 27:314-324.
Luders E., Sanchez F.J., Gaser C., Toga A.W., Narr K.L., Hamilton L.S., Vilain E. Regional gray matter variation in male-to-female transsexualism. NeuroImage 2009, 46:904-907.
Luders E., Sanchez F.J., Tosun D., Shattuck D.W., Gaser C., Vilain E., Toga A.W. Increased cortical thickness in male-to-female transsexualism. J. Behav. Brain Sci. 2012, 2:357-362.
Matsumoto A., Arai Y. Sex difference in volume of the ventromedial nucleus of the hypothalamus in the rat. Endocrinol. Jpn. 1983, 30:277-280.
McCarthy M.M. Estradiol and the developing brain. Physiol. Rev. 2008, 88:91-124.
Rametti G., Carrillo B., Gomez-Gil E., Junque C., Segovia S., Gomez A., Guillamon A. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. J. Psychiatr. Res. 2011, 45:199-204.
Rametti G., Carrillo B., Gomez-Gil E., Junque C., Zubiarre-Elorza L., Segovia S., Gomez A., Guillamon A. The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study. J. Psychiatr. Res. 2011, 45:949-954.
Raz N., Gunning-Dixon F., Head D., Williamson A., Acker J.D. Age and sex differences in the cerebellum and the ventral pons: a prospective MR study of healthy adults. AJNR Am. J. Neuroradiol. 2001, 22:1161-1167.
Savic I., Arver S. Sex dimorphism of the brain in male-to-female transsexuals. Cereb. Cortex 2011, 21:2525-2533.
Savic I., Garcia-Falgueras A., Swaab D.F. Sexual differentiation of the human brain in relation to gender identity and sexual orientation. Prog. Brain Res. 2010, 186:41-62.
Schrouff J., Rosa M.J., Rondina J.M., Marquand A.F., Chu C., Ashburner J., Phillips C., Richiardi J., Mourao-Miranda J. PRoNTo: pattern recognition for neuroimaging toolbox. Neuroinformatics 2013, 11:319-337.
Simon L., Kozak L.R., Simon V., Czobor P., Unoka Z., Szabo A., Csukly G. Regional grey matter structure differences between transsexuals and healthy controls--a voxel based morphometry study. PLoS ONE 2013, 8:e83947.
Smith Y.L., van Goozen S.H., Kuiper A.J., Cohen-Kettenis P.T. Sex reassignment: outcomes and predictors of treatment for adolescent and adult transsexuals. Psychol. Med. 2005, 35:89-99.
Swaab D.F. Sexual differentiation of the brain and behavior. Best Pract. Res. Clin. Endocrinol. Metab. 2007, 21:431-444.
Swaab D.F., Fliers E. A sexually dimorphic nucleus in the human brain. Science 1985, 228:1112-1115.
Tanner J. Growth at Adolescence 1962, Blackwell Scientific Publications; Oxford, UK.
Tiemeier H., Lenroot R.K., Greenstein D.K., Tran L., Pierson R., Giedd J.N. Cerebellum development during childhood and adolescence: a longitudinal morphometric MRI study. NeuroImage 2010, 49:63-70.
Verhulst, F.C., van der Ende, J., Koot, H.M., 1996. Handleiding voor de CBCL-4/18 [Manual for the CBCL/4-18], Sophia Kinderziekenhuis, Erasmus MC; Rotterdam, the Netherlands.
Wechsler D. Wechsler Adult Intelligence Scale-Third Edition 1997, The Psychological Corporation, San Antonio, TX.
Wechsler D. Wechsler Intelligence Scale for Children-Third Edition 1991, The Psychological Corporation, San Antonio, TX.
Wisniewski A.B., Migeon C.J., Meyer-Bahlburg H.F., Gearhart J.P., Berkovitz G.D., Brown T.R., Money J. Complete androgen insensitivity syndrome: long-term medical, surgical, and psychosexual outcome. J. Clin. Endocrinol. Metab. 2000, 85:2664-2669.
Zhou J.N., Hofman M.A., Gooren L.J., Swaab D.F. A sex difference in the human brain and its relation to transsexuality. Nature 1995, 378:68-70.
Zubiaurre-Elorza L., Junque C., Gomez-Gil E., Guillamon A. Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals. J. Sex. Med. 2014, 11:1248-1261.
Zubiaurre-Elorza L., Junque C., Gomez-Gil E., Segovia S., Carrillo B., Rametti G., Guillamon A. Cortical Thickness in Untreated Transsexuals. Cereb. Cortex 2012, 23(12):2855-2862.
