Brain activity changes in transgender women with gender dysphoria linked to childhood trauma, genes and neurotransmitters

Transgender women with gender dysphoria show distinct patterns of resting brain activity, and those patterns are linked to childhood traumatic experiences, particularly emotional neglect, according to a new study published in BMC Medicine. The research, released as an early peer-reviewed, accepted version on 23 October 2026, also ties the altered brain activity to gene expression patterns and to dopaminergic and serotonergic neurotransmission, offering what the authors describe as a multilevel neurophysiological framework for understanding gender dysphoria.

The study was motivated by an open question in the field. Although early-life stress and trauma may influence cortical development and increase vulnerability to gender dysphoria, the relationship between brain function and childhood traumatic experiences in gender dysphoria had remained unexplored. The researchers set out to examine functional brain alterations and their associations with childhood trauma, neurotransmitter systems and gene expression patterns.

To do so, the team recruited 44 transgender women with gender dysphoria, along with 40 cisgender men and 42 cisgender women as controls. Participants completed the Childhood Trauma Questionnaire (CTQ) and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA).

The imaging results pointed to a specific spatial pattern. In a comparison restricted to cisgender women, the transgender women showed decreased fALFF in the right PCC. The authors characterize this combination as PCC hypofunction alongside cerebellar hyperactivation.

The questionnaire data added a behavioral dimension. Transgender women with gender dysphoria reported higher CTQ total scores and higher subscale scores than the cisgender control groups, indicating greater reported childhood trauma. GIDYQ-AA scores, which index gender dysphoria severity, were negatively correlated with ALFF in the PCC, meaning lower activity in that region was associated with higher dysphoria scores.

The links between trauma and brain function were also specific. CTQ total scores and its subscale scores for emotional abuse and emotional neglect were negatively correlated with decreased ALFF in the PCC. In other words, participants who reported more childhood trauma, especially emotional neglect, tended to show lower spontaneous activity in the posterior cingulate cortex.

Multivariate regression analysis strengthened the case that these relationships are interactive rather than merely parallel. The analysis revealed that the interaction between the fALFF value of the right PCC and CTQ total scores, and the interaction between the right PCC fALFF value and emotional neglect scores, independently predicted GIDYQ-AA scores among the transgender women with gender dysphoria. This suggests that the combination of altered PCC activity and childhood trauma history, particularly emotional neglect, carries information about the severity of gender dysphoria beyond either factor alone.

To probe the biology underlying the altered activity, the researchers turned to two complementary resources. Transcriptional data were sourced from the Allen Human Brain Atlas, and the JuSpace toolbox was used to investigate atlas-based nuclear imaging-derived neurotransmitter maps.

The authors conclude that transgender women with gender dysphoria show PCC hypofunction and cerebellar hyperactivation, which are associated with childhood trauma, especially emotional neglect, and that these neural alterations are correlated with gene expression and neurotransmitter pathways. They present this as suggesting a multilevel neurophysiological framework in transgender women with gender dysphoria.

Subject of Research: Neuroimaging of brain activity, childhood trauma, gene expression and neurotransmitter associations in transgender women with gender dysphoria

Article Title: Altered brain activity and childhood trauma associate with gene and neurotransmitter patterns in transgender women with gender dysphoria

Article References: Chen, R., Chen, G., Sun, S., Chen, P., Guo, Z., Liao, M., Chen, C., Tang, X., Qi, Z., Li, J., Wu, X., Zhang, X., Liang, J., Zhong, S., & Wang, Y. (2026). Altered brain activity and childhood trauma associate with gene and neurotransmitter patterns in transgender women with gender dysphoria. BMC Medicine. https://doi.org/10.1186/s12916-026-05305-w

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05305-w

Keywords: gender dysphoria, transgender women, resting-state fMRI, posterior cingulate cortex, childhood trauma, emotional neglect, ALFF, cerebellum, dopamine, serotonin, Allen Human Brain Atlas, BMC Medicine