Neurobiological characteristics associated with gender identity: Findings from neuroimaging studies in the Amsterdam cohort of children and adolescents experiencing gender incongruence

This review has been based on my invited lecture at the annual meeting of the Society for Behavioral Neuroendocrinology in 2023. Gender incongruence is defined as a marked and persistent incongruence between an individual's experienced gender and the sex assigned at birth. A prominent hypothesis on the etiology of gender incongruence proposes that it is related to an altered or less pronounced sexual differentiation of the brain. This hypothesis has primarily been based on postmortem studies of the hypothalamus in transgender individuals. To further address this hypothesis, a series of structural and functional neuroimaging studies were conducted in the Amsterdam cohort of children and adolescents experiencing gender incongruence. Additional research objectives were to determine whether any sex and gender differences are established before or after puberty, as well as whether gender affirming hormone treatment would affect brain development and function. We found some evidence in favor of the sexual differentiation hypothesis at the functional level, but this was less evident at the structural level. We also observed some specific transgender neural signatures, suggesting that they might present a unique brain phenotype rather than being shifted towards either end of the male-female spectrum. Our results further suggest that the years between childhood and mid-adolescence represent an important period in which puberty-related factors influence several neural characteristics, such as white matter development and functional connectivity patterns, in both a sex and gender identity specific way. These latter observations thus lead to the important question about the possible negative consequences of delaying puberty on neurodevelopment. To further address this question, larger-scale, longitudinal studies are required to increase our understanding of the possible neurodevelopmental impacts of delaying puberty in transgender youth.