Dialogues in Clinical Neuroscience · Available online 13 May 2026 · In press · DOI 10.1080/19585969.2026.2669514
Guanmao Chen, Ruoyi Chen, Mengqi Liao, Shilin Sun, Pan Chen, Zixuan Guo, Chao Chen, Xinyue Tang, Zhangzhang Qi, Shuming Zhong, Lvfen Gao, Xiaoxing Huang, Xuehong Xiao, Ying Wang
Introduction Gender dysphoria (GD) causes distress from gender-sex incongruence with elevated suicide risk, yet its neuropathology remains unclear. The thalamic-cortical functional connectivity (FC) in transgender women (TW) is unexplored. We investigated thalamo-cortical FC and its mediating role in TW’s symptom-cognition relationships.Methods We retrospectively analysed resting-state fMRI from 44 TW, 40 cisgender men (CM), and 42 cisgender women (CW), between October 2021 and January 2024. Clinical symptoms (GIDYQ-AA) and cognition (MCCB) were assessed. Seed-based thalamic subregion FC and mediation analyses were performed.Results Relative to CW, TW and CM exhibited increased FC in multiple thalamo-prefrontal circuits. Compared to CM, TW showed decreased left mPFtha-left DLPFC FC (p = 0.026), and right rTtha-left DLPFC FC (p = 0.025). Compared to CM, right PPtha-right MOG FC (p = 0.023; p < 0.001), and right cTtha-right SOG FC (p = 0.008; p < 0.001) were increased in TW and CW. In TW, left rTtha-bilateral MPFC FC correlated with GIDYQ-AA scores, attention/vigilance, and composite. This FC fully mediated relationships between GD symptoms and both attention/vigilance (bootstrapped 95% CI = 1.861–11.688) and composite (bootstrapped 95% CI = 1.025–12.283).Conclusions TW exhibit thalamo-cortical FC abnormalities and cognitive dysfunction. Critically, thalamus-MPFC dysconnectivity mediates GD symptom-related cognitive dysfunction, revealing a novel neural pathway. Validation in larger, diverse samples is needed.
Abstract from DOAJ. Public domain (CC0 1.0).
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Chen, G., Chen, R., Liao, M., et al. (2026). Comparisons of thalamocortical functional connectivity in transgender women and cisgender individuals: associations with cognition in a Chinese cohort. Dialogues in Clinical Neuroscience. https://doi.org/10.1080/19585969.2026.2669514