Understanding attenuated positive facial expression in depressed women: central role of dorsal raphe network alterations and associated serotonin transporter methylation.

Anhedonia and loss of pleasure are core features of major depressive disorder, yet their neurobiological basis remains unclear. We examined dynamic facial responses to naturalistic emotional video stimuli in women with major depressive disorder and healthy controls using automated facial expression analysis. Functional MRI combined with tensor-independent component analysis identified brain networks associated with facial expressivity, and targeted DNA methylation analysis was also conducted. Women with depression showed significantly reduced positive facial expressions in response to joyful stimuli, whereas negative facial responses to sad stimuli did not differ between groups. Positive facial expression was associated with the dynamic brain response to emotional video clips measured by fMRI in the dorsal raphe network. We also found the higher temporal coupling between dorsal raphe and epithalamus/periaqueductal gray, and the higher methylation level of serotonin transporter gene in women with depression. Increased methylation levels of SLC6A4 were associated with the enhanced functional connectivity. These findings indicate that altered coordination within a dorsal raphe-centered network underlies attenuated positive facial expression in depressed women, and that this network connectivity is associated with serotonin transporter methylation.