The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group

Sven C Mueller; Antonio Guillamon; Leire Zubiaurre-Elorza; Carme Junque; Esther Gomez-Gil; Carme Uribe; Behzad S Khorashad; Behnaz Khazai; Ali Talaei; Ute Habel; Mikhail Votinov; Birgit Derntl; Rupert Lanzenberger; Rene Seiger; Georg S Kranz; Baudewijntje P C Kreukels; Peggy T Cohen Kettenis; Sarah M Burke; Nils B Lambalk; Dick J Veltman; Mathilde Kennis; Francisco J Sánchez; Eric Vilain; Alessandra Daphne Fisher; Mario Mascalchi; Gioele Gavazzi; Stefano Orsolini; Jiska Ristori; Udo Dannlowski; Dominik Grotegerd; Carsten Konrad; Maiko Abel Schneider; Guy T'Sjoen; Eileen Luders

doi:10.1016/j.jsxm.2021.03.079

The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group

J Sex Med. 2021 Jun;18(6):1122-1129. doi: 10.1016/j.jsxm.2021.03.079. Epub 2021 May 22.

Authors

Sven C Mueller¹, Antonio Guillamon², Leire Zubiaurre-Elorza³, Carme Junque⁴, Esther Gomez-Gil⁵, Carme Uribe⁴, Behzad S Khorashad⁶, Behnaz Khazai⁷, Ali Talaei⁸, Ute Habel⁹, Mikhail Votinov⁹, Birgit Derntl¹⁰, Rupert Lanzenberger¹¹, Rene Seiger¹¹, Georg S Kranz¹², Baudewijntje P C Kreukels¹³, Peggy T Cohen Kettenis¹³, Sarah M Burke¹⁴, Nils B Lambalk¹⁵, Dick J Veltman¹⁶, Mathilde Kennis¹⁷, Francisco J Sánchez¹⁸, Eric Vilain¹⁹, Alessandra Daphne Fisher²⁰, Mario Mascalchi²¹, Gioele Gavazzi²², Stefano Orsolini²³, Jiska Ristori²⁴, Udo Dannlowski²⁵, Dominik Grotegerd²⁵, Carsten Konrad²⁶, Maiko Abel Schneider²⁷, Guy T'Sjoen²⁸, Eileen Luders²⁹

Affiliations

¹ Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium; Department of Personality, Psychological Assessment and Treatment, University of Deusto, Bilbao, Spain. Electronic address: Sven.Mueller@UGent.be.
² Deparment of Psychobiology, National Distance Education University, Madrid, Spain.
³ Department of Methods and Experimental Psychology, Faculty of Psychology and Education, University of Deusto, Bilbao, Spain.
⁴ Department of Medicine, Institute of Neuroscience, IDIBAPS, University of Barcelona.
⁵ Gender Identity Unit, Clinic Hospital, Barcelona, Spain.
⁶ Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Women's and Children's Health, Karolinska University Hospital, Karolinska Institute, Solna, Stockholm, Sweden.
⁷ Keck School of Medicine, Mark and Mary Stevens Neuroimaging and Informatics Institute, USC, Los Angeles, CA, USA.
⁸ Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
⁹ Department of Psychiatry, Psychotherapy, and Psychosomatics, University Clinic RWTH, Aachen, Germany; Research Centre Jülich, Institute of Neuroscience and Medicine (INM-10), Jülich, Germany.
¹⁰ Deptarment of Psychiatry and Psychotherapy, University of Tuebingen, Germany.
¹¹ Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
¹² Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hongkong.
¹³ Medical Psychology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
¹⁴ Psychology, Developmental and Educational Psychology, University of Leiden, Leiden, The Netherlands.
¹⁵ Obstetrics and Gynaecology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
¹⁶ Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands.
¹⁷ Department of Cognitive Neuroscience, Maastricht University, Maastricht, The Netherlands.
¹⁸ College of Education, University of Missouri, MO, USA.
¹⁹ Center for Genetic Medicine Research, Children's National Hospital, Washington DC, USA; Department of Genomics and Precision Medicine, George Washington University, Washington, DC, USA.
²⁰ Andrology, Women's Endocrinology, Gender Incongruence Unit, Careggi University Hospital, Florence, Italy.
²¹ Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
²² Department of Neuroscience, Psychology, Drug Research, Child Health, University of Florence, Florence, Italy.
²³ Department of Electrical, Electronic, and Information Engineering "Guglielmo Marconi", University of Bologna, Cesena, Italy.
²⁴ Center for Genetic Medicine Research, Children's National Hospital, Washington DC, USA.
²⁵ Institute for Translational Psychiatry, University of Muenster, Muenster, Germany.
²⁶ Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum, Rotenburg, Germany.
²⁷ McMaster University, Hamilton, Canada.
²⁸ Department of Endocrinology & Center for Sexology and Gender, Ghent University Hospital, Ghent, Belgium.
²⁹ School of Psychology, University of Auckland, Auckland, New Zealand.

PMID: 34030966
DOI: 10.1016/j.jsxm.2021.03.079

Abstract

Background: In contrast to cisgender persons, transgender persons identify with a different gender than the one assigned at birth. Although research on the underlying neurobiology of transgender persons has been accumulating over the years, neuroimaging studies in this relatively rare population are often based on very small samples resulting in discrepant findings.

Aim: To examine the neurobiology of transgender persons in a large sample.

Methods: Using a mega-analytic approach, structural MRI data of 803 non-hormonally treated transgender men (TM, n = 214, female assigned at birth with male gender identity), transgender women (TW, n = 172, male assigned at birth with female gender identity), cisgender men (CM, n = 221, male assigned at birth with male gender identity) and cisgender women (CW, n = 196, female assigned at birth with female gender identity) were analyzed.

Outcomes: Structural brain measures, including grey matter volume, cortical surface area, and cortical thickness.

Results: Transgender persons differed significantly from cisgender persons with respect to (sub)cortical brain volumes and surface area, but not cortical thickness. Contrasting the 4 groups (TM, TW, CM, and CW), we observed a variety of patterns that not only depended on the direction of gender identity (towards male or towards female) but also on the brain measure as well as the brain region examined.

Clinical translation: The outcomes of this large-scale study may provide a normative framework that may become useful in clinical studies.

Strengths and limitations: While this is the largest study of MRI data in transgender persons to date, the analyses conducted were governed (and restricted) by the type of data collected across all participating sites.

Conclusion: Rather than being merely shifted towards either end of the male-female spectrum, transgender persons seem to present with their own unique brain phenotype. Mueller SC, Guillamon A, Zubiaurre-Elorza L, et al. The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group. J Sex Med 2021;18:1122-1129.

Keywords: Anatomy; ENIGMA; MRI; Mega-analysis; Sex differences; Transgender.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Brain / diagnostic imaging
Female
Gender Identity
Humans
Male
Neuroanatomy
Transgender Persons*
Transsexualism* / diagnostic imaging

Abstract

Publication types

MeSH terms

Grants and funding