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

Pia Baldinger-Melich, Maria F. Urquijo Castro, Rene Seiger, Anne Ruef, Dominic B. Dwyer, Georg S. Kranz, Manfred Kloebl, Joseph Kambeitz, Ulrike Kaufmann, Christian Windischberger, Siegfried Kasper, Peter Falkai, Rupert Lanzenberger, Nikolaos Koutsouleris

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22 Citations (Scopus)


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 [p FDR] < 0.001) in cisgender, but only with 67.5% (p FDR = 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 p FDR > 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).

Original languageEnglish
Pages (from-to)1345-1356
Number of pages12
JournalCerebral Cortex
Issue number3
Publication statusPublished - 14 Mar 2020


  • gender identity
  • gender incongruence
  • multivariate pattern analysis
  • sex differences
  • structural magnetic resonance imaging

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