Sex Matters: A Multivariate Pattern Analysis of Sex- and Gender-Related Neuroanatomical Differences in Cis- and Transgender Individuals Using Structural Magnetic Resonance Imaging

• Published in: Cerebral cortex (New York, N.Y. 1991) Vol. 30; no. 3; pp. 1345 - 1356
• Main Authors: Baldinger-Melich, Pia, Urquijo Castro, Maria F, Seiger, René, Ruef, Anne, Dwyer, Dominic B, Kranz, Georg S, Klöbl, Manfred, Kambeitz, Joseph, Kaufmann, Ulrike, Windischberger, Christian, Kasper, Siegfried, Falkai, Peter, Lanzenberger, Rupert, Koutsouleris, Nikolaos
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 14.03.2020
• Subjects: Adult; Brain - anatomy & histology; Brain - diagnostic imaging; Female; Gender Identity; Gray Matter - anatomy & histology; Gray Matter - diagnostic imaging; Humans; Magnetic Resonance Imaging; Male; Multivariate Analysis; Organ Size; Original; Sex Characteristics; Transgender Persons; Young Adult; structural magnetic resonance imaging; gender identity; multivariate pattern analysis; gender incongruence; sex differences
• ISSN: 1047-3211; 1460-2199; 1460-2199
• DOI: 10.1093/cercor/bhz170

Abstract Univariate analyses of structural neuroimaging data have produced heterogeneous results regarding anatomical sex- and gender-related differences. The current study aimed at delineating and cross-validating brain volumetric surrogates of sex and gender by comparing the structural magnetic resonance imaging data of cis- and transgender subjects using multivariate pattern analysis. Gray matter (GM) tissue maps of 29 transgender men, 23 transgender women, 35 cisgender women, and 34 cisgender men were created using voxel-based morphometry and analyzed using support vector classification. Generalizability of the models was estimated using repeated nested cross-validation. For external validation, significant models were applied to hormone-treated transgender subjects (n = 32) and individuals diagnosed with depression (n = 27). Sex was identified with a balanced accuracy (BAC) of 82.6% (false discovery rate [pFDR] < 0.001) in cisgender, but only with 67.5% (pFDR = 0.04) in transgender participants indicating differences in the neuroanatomical patterns associated with sex in transgender despite the major effect of sex on GM volume irrespective of the self-identification as a woman or man. Gender identity and gender incongruence could not be reliably identified (all pFDR > 0.05). The neuroanatomical signature of sex in cisgender did not interact with depressive features (BAC = 74.7%) but was affected by hormone therapy when applied in transgender women (P < 0.001).