Background: Depression is characterized by enhanced self-referential processing of negative emotional stimuli. Imaging studies have suggested that activation of both the medial prefrontal (MPFC) and anterior cingulate cortices (ACC) is associated with self-referential processing. However, whether this pattern of activation occurs in depressed individuals during the self-referential processing of the emotional stimuli had not been investigated to date. Methods: Participants were 13 patients with major depressive disorder and 13 normal controls. We used block-designed functional magnetic resonance imaging (fMRI) to investigate neural activity during the self-referential judgments of positive and negative valenced personality trait words. Results: Compared with the normal controls, the depressed patients showed hyperactivity in the MPFC and the rostral ACC during the self-referential processing of negative words. In addition, the activity of these regions during self-referential processing of the negative stimuli was correlated with the depressive symptom severity. The rostral ACC activity mediated the correlation between the MPFC activity and the depressive symptoms. Functional connectivity analysis revealed positive connectivities between the MPFC, the rostral ACC, and the amygdala. Limitation: Small N and antidepressant effect on imaging data limit the stability of reported findings. Conclusions: The relationships between the MPFC, the rostral ACC, and the amygdala appear to reflect an interaction between the self-referential processing and the negative emotional information processing, and we propose that the strong connection between the MPFC and the rostral ACC is associated with depressive symptoms.
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