Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus

Background: Positron emission tomography (PET) studies of major depression have revealed resting-state abnormalities in the prefrontal and cingulate cortices. Recently, fMRI has been adapted to examine connectivity within a specific resting-state neural network-the default-mode network-that includes medial prefrontal and anterior cingulate cortices. The goal of this study was to examine resting-state, default-mode network functional connectivity in subjects with major depression and in healthy controls. Methods: Twenty-eight subjects with major depression and 20 healthy controls underwent 5-min fMRl scans while resting quietly. Independent component analysis was used to isolate the default-mode network in each subject. Group maps of the default-mode network were compared. A within-group analysis was performed in the depressed group to explore effects of depression refractoriness on functional connectivity. Results: Resting-state subgenual cingulate and thalamic functional connectivity with the default-mode network were significantly greater in the depressed subjects. Within the depressed group, the length of the current depressive episode correlated positively with functional connectivity in the subgenual cingulate. Conclusions: This is the first study to explore default-mode functional connectivity in major depression. The findings provide crossmodality confirmation of PET studies demonstrating increased thalamic and subgenual cingulate activity in major depression. Further, the within-subject connectivity analysis employed here brings these previously isolated regions of hypermetabolism into the context of a disordered neural network. The correlation between refractoriness and subgenual cingulate functional connectivity within the network suggests that a quantitative, resting-state fMRI measure could be used to guide therapy in individual subjects.