TY - JOUR
T1 - Sex Matters
T2 - A Multivariate Pattern Analysis of Sex- and Gender-Related Neuroanatomical Differences in Cis- and Transgender Individuals Using Structural Magnetic Resonance Imaging
AU - Baldinger-Melich, Pia
AU - Urquijo Castro, Maria F.
AU - Seiger, René
AU - Ruef, Anne
AU - Dwyer, Dominic B.
AU - Kranz, Georg S.
AU - Klöbl, Manfred
AU - Kambeitz, Joseph
AU - Kaufmann, Ulrike
AU - Windischberger, Christian
AU - Kasper, Siegfried
AU - Falkai, Peter
AU - Lanzenberger, Rupert
AU - Koutsouleris, Nikolaos
PY - 2020/3/14
Y1 - 2020/3/14
N2 - 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).
AB - 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).
KW - gender identity
KW - gender incongruence
KW - multivariate pattern analysis
KW - sex differences
KW - structural magnetic resonance imaging
UR - http://www.scopus.com/inward/record.url?scp=85079433005&partnerID=8YFLogxK
U2 - 10.1093/cercor/bhz170
DO - 10.1093/cercor/bhz170
M3 - Journal article
C2 - 31368487
AN - SCOPUS:85079433005
SN - 1047-3211
VL - 30
SP - 1345
EP - 1356
JO - Cerebral Cortex
JF - Cerebral Cortex
IS - 3
ER -