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). 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. The TPR did not differ between CG-individuals with (TPR-male = 86.9%) and without depression (TPR-male = 88.5%).
The application of our biological sex classifier to the transgender sample resulted in a significantly lower true positive rate (TPR-male = 56.0%). 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. Subsequently, the classifier was applied to N = 26 TW. A third validation was performed using the matched CG sample of the transgender women (TW) application sample. As a second validation, we classified N = 1104 patients with depression.
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. To substantiate evidence that the brain structure of TIs differs from male and female, we use a combined multivariate and univariate approach. Transgender individuals (TIs) show brain-structural alterations that differ from their biological sex as well as their perceived gender.
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