A Treatment-Resistant Default Mode Subnetwork in Major Depression

Background: Previous studies have suggested that the default mode network (DMN) plays a central role in the physiopathology of major depressive disorder (MDD). However, the effect of antidepressant treatment on functional connectivity within the DMN has yet to be established. Considering the very high rates of relapse in recovered subjects, we hypothesized that abnormalities in DMN functional connectivity would persist in recovered MDD subjects. Methods: Resting state functional magnetic resonance imaging images were collected from 24 MDD patients and 29 healthy control subjects. After 12 weeks of antidepressant treatment, 18 recovered MDD subjects were scanned again. Group independent component analysis was performed to decompose the resting state images into spatially independent components. Default mode subnetworks were identified using a template based on previous studies. Group differences in the ensuing subnetworks were tested using two-sample t tests. Results: Two spatially independent default mode subnetworks were detected in all subjects: the anterior subnetwork and the posterior subnetwork. Both subnetworks showed increased functional connectivity in pretreatment MDD subjects, relative to control subjects. Differences in the posterior subnetwork were normalized after antidepressant treatment, while abnormal functional connectivity persisted within the anterior subnetwork. Conclusions: Our findings suggest a dissociation of the DMN into subnetworks, where persistent abnormal functional connectivity within the anterior subnetwork in recovered MDD subjects may constitute a biomarker of asymptomatic depression and potential for relapse.