Abstract
The risk of relapsing into depression after stopping antidepressants is high, but no established predictors exist. Resting-state functional magnetic resonance imaging (rsfMRI) measures may help predict relapse and identify the mechanisms by which relapses occur. rsfMRI data were acquired from healthy controls and from patients with remitted major depressive disorder on antidepressants. Patients were assessed a second time either before or after discontinuation of the antidepressant, and followed up for six months to assess relapse. A seed-based functional connectivity analysis was conducted focusing on the left subgenual anterior cingulate cortex and left posterior cingulate cortex. Seeds in the amygdala and dorsolateral prefrontal cortex were explored. 44 healthy controls (age: 33.8 (10.5), 73% female) and 84 patients (age: 34.23 (10.8), 80% female) were included in the analysis. 29 patients went on to relapse and 38 remained well. The seed-based analysis showed that discontinuation resulted in an increased functional connectivity between the right dorsolateral prefrontal cortex and the parietal cortex in non-relapsers. In an exploratory analysis, this functional connectivity predicted relapse risk with a balanced accuracy of 0.86. Further seed-based analyses, however, failed to reveal differences in functional connectivity between patients and controls, between relapsers and non-relapsers before discontinuation and changes due to discontinuation independent of relapse. In conclusion, changes in the connectivity between the dorsolateral prefrontal cortex and the posterior default mode network were associated with and predictive of relapse after open-label antidepressant discontinuation. This finding requires replication in a larger dataset.
Highlights
A subset of those suffering from Major Depressive Disorder (MDD) achieve remission with antidepressant medication (ADM)[1]
Abnormal resting-state functional connectivity (RSFC) in MDD has been observed in three core networks, i.e. the so-called "default mode network" (DMN), the central executive network (CEN) and the salience network (SN)
We aimed to address these gaps in the context of the AIDA study—a two-centre observational randomized study that followed patients as they discontinued their ADM for six months
Summary
A subset of those suffering from Major Depressive Disorder (MDD) achieve remission with antidepressant medication (ADM)[1]. Connectivity changes in these regions have been observed in remitted patients off medication and in populations with correlates of depression such as trauma, childhood maltreatment, subclinical depression and familial risk in children. These include increased connectivity between the sgACC and both the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC), as well as bidirectional changes in connectivity between the sgACC and the dorsolateral PFC (dlPFC), the amygdala and the hippocampus(15–24; though see 25). Increases between the PCC and the ACC and mPFC have been reported in patients who receive treatment, but do not r emit[32]
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