Biological sex classification with structural MRI data shows increased misclassification in transgender women

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • C. Flint - , University of Münster (Joint first author)
  • K. Förster - , University of Münster (Joint first author)
  • S.A. Koser - , University of Münster (Author)
  • Carsten Konrad - , Agaplesion Diakonieklinikum Rotenburg (Author)
  • P. Zwitserlood - , University of Münster (Author)
  • Klaus Berger - , University of Münster (Author)
  • M. Hermesdorf - , University of Münster (Author)
  • Tilo Kircher - , University of Münster (Author)
  • I. Nenadic - , University of Münster (Author)
  • A. Krug - (Author)
  • B.T. Baune - , University of Melbourne, University of Münster (Author)
  • K. Dohm - , University of Münster (Author)
  • R. Redlich - , University of Münster (Author)
  • N. Opel - , University of Münster (Author)
  • Volker Arolt - , University of Münster (Author)
  • Tim Hahn - , University of Münster (Author)
  • X. Jiang - , University of Münster (Author)
  • U. Dannlowski - , University of Münster (Author)
  • D. Grotegerd - , University of Münster (Author)

Abstract

Transgender individuals (TIs) show brain-structural alterations that differ from their biological sex as well as their perceived gender. To substantiate evidence that the brain structure of TIs differs from male and female, we use a combined multivariate and univariate approach. Gray matter segments resulting from voxel-based morphometry preprocessing of N = 1753 cisgender (CG) healthy participants were used to train (N = 1402) and validate (20% holdout N = 351) a support-vector machine classifying the biological sex. As a second validation, we classified N = 1104 patients with depression. A third validation was performed using the matched CG sample of the transgender women (TW) application sample. Subsequently, the classifier was applied to N = 26 TW. Finally, we compared brain volumes of CG-men, women, and TW-pre/post treatment cross-sex hormone treatment (CHT) in a univariate analysis controlling for sexual orientation, age, and total brain volume. The application of our biological sex classifier to the transgender sample resulted in a significantly lower true positive rate (TPR-male = 56.0%). The TPR did not differ between CGindividuals with (TPR-male = 86.9%) and without depression (TPR-male = 88.5%). The univariate analysis of the transgender application-sample revealed that TW-pre/post treatment show brain-structural differences from CG-women and CG-men in the putamen and insula, as well as the whole-brain analysis. Our results support the hypothesis that brain structure in TW differs from brain structure of their biological sex (male) as well as their perceived gender (female). This finding substantiates evidence that TIs show specific brain-structural alterations leading to a different pattern of brain structure than CG-individuals.

Details

Original languageEnglish
Pages (from-to)1758-1785
Number of pages8
JournalNeuropsychopharmacology
Volume45
Issue number10
Publication statusPublished - 9 Apr 2020
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 85083786941

Keywords

Library keywords