Depression and the Prefrontal-Hippocampal Pathway - A Pilot Multimodal Neuroimaging Study in Transgender Women

This pilot study explored associations between gamma-aminobutyric acid (GABA) spectroscopy and functional magnetic resonance imaging in transgender women with depression. Twenty participants completed mental health surveys and imaging between January and March 2024. Depression severity was measured by Patient Health Questionnaire-9 (PHQ-9) scores. Higher PHQ-9 scores were associated with lower GABA levels in the hippocampus and lower fractional amplitude of low-frequency fluctuations (fALFF) in the dorsolateral prefrontal cortex. These findings revealed interactions between neurotransmitter signaling and functional brain activity of the hippocampal-prefrontal circuit in depression. Future large-scale neuroimaging studies are needed.