Decreased functional coupling of the amygdala and supragenual cingulate is related to increased depression in unmedicated individuals with current major depressive disorder

Background: Individuals with major depressive disorder (MDD) show abnormal functional coupling (FC) between several nodes of a widely distributed cortico-limbic network that includes the amygdala and anterior cingulate. The aim of this study was to examine the degree to which alterations in amygdala-cingulate FC relate to severity of current depressive symptoms in a group of depressed individuals without significant co-morbidities. Methods: Fifteen young, unmedicated subjects with current MDD and 16 healthy controls (HC) with no lifetime history of psychiatric illness performed a validated emotional face-matching task during functional magnetic resonance imaging. Amygdala activity and strength of amygdala-cingulate FC during emotional face processing were contrasted between the groups. Results: Although both groups activated the extended amygdala, (EA) during emotion processing, the MDD relative to the HC group showed more task-related co-activation of the subgenual cingulate, which is involved in processing negative self-referential information; and less co-activation of the supragenual cingulate, which is involved in the cognitive control of emotion. Greater depressive symptom severity correlated positively with decreased FC between bilateral EA and supragenual cingulate in MDD subjects. Limitations: This study included a demographically homogeneous population of subjects, which may limit the generalizability of the findings. Conclusions: These results elaborate current neurobiological models of MDD by providing unique evidence that decreased FC between the EA and supragenual cingulate is related to increased severity of current depressive symptoms. We speculate that the clinical manifestations of MDD may result in part from a failed ability to co-activate a cognitive control network during emotion processing. Published by Elsevier B.V