Inter-Network Brain Functional Connectivity in Adolescents Assigned Female at Birth Who Experience Gender Dysphoria

Abstract

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Brain functional connectivity in adolescents who experience GD may be associated with experienced gender (vs. assigned sex) and/or brain networks implicated in own-body perception. Furthermore, sexual orientation may be related to brain functional organization given commonalities in developmental mechanisms proposed to underpin GD and same-sex attractions. Here, we applied group independent component analysis to resting-state functional magnetic resonance imaging (rs-fMRI) BOLD timeseries data to estimate inter-network (i.e., between independent components) timeseries correlations, representing functional connectivity, in 17 GD adolescents assigned female at birth (AFAB) not receiving gender-affirming hormone therapy, 17 cisgender girls, and 15 cisgender boys (ages 12-17 years). Sexual orientation was represented by degree of androphilia-gynephilia and sexual attractions strength. Multivariate partial least squares analyses found that functional connectivity differed among cisgender boys, cisgender girls, and GD AFAB, with the largest difference between cisgender boys and GD AFAB. Regarding sexual orientation and age, the brain’s intrinsic functional organization of GD AFAB was both similar to and different from cisgender girls, and both differed from cisgender boys. The pattern of group differences and the networks involved aligned with the hypothesis that brain functional organization is different among GD AFAB (vs. cisgender) adolescents, and certain aspects of this organization relate to brain areas implicated in own-body perception and self-referential thinking. Overall, brain functional organization of GD AFAB was generally more similar to that of cisgender girls than cisgender boys.

Cortical Structure Differences in Relation to Age, Sexual Attractions, and Gender Dysphoria in Adolescents: An Examination of Mean Diffusivity and T1 Relaxation Time

“…Table 1 also shows the omnibus results from the ANOVAs for age, the GIDYQ-AA, the strength of attractions, and the degree of androphilia–gynephilia. The results did not differ from Skorska et al [ 8 ] or Skorska et al [ 28 ] and are thus summarized here. Details can be found in the Supplementary Materials .…”

“…Data from five additional participants were removed: data from one GD AFAB adolescent were removed due to excessive artifacts from a metal orthodontic expander, data from one GD AFAB adolescent were removed due to an unusable MD map, data from one cisgender boy were removed due to excessive head motion during T1-weighted (T1w) scans, and data from one GD AFAB adolescent and one cisgender boy were removed because the images needed to calculate the T1 maps were unusable. Forty-seven of the participants were included in Skorska et al [ 8 ], and forty-nine participants were included in Skorska et al [ 28 ].…”

White matter microstructure in transmasculine and cisgender adolescents: A multiparametric and multivariate study

“…Thus, this study included 46 individuals aged 12 to 17 years (mean = 15.4 years; standard deviation, [SD] = 1.66). Structural and functional magnetic resonance imaging (MRI) data from a largely overlapping cohort of these participants have previously been published [ 39 , 44 ]; the WM metrics reported here have not yet been published. Data were collected from 2014 to 2018 at the Centre for Addiction and Mental Health (CAMH) in Toronto, Canada.…”