The relationship between resting-state functional connectivity, antidepressant discontinuation and depression relapse

Sci Rep. 2020 Dec 18;10(1):22346. doi: 10.1038/s41598-020-79170-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amygdala / diagnostic imaging
  • Amygdala / pathology
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Brain Mapping
  • Depression / complications
  • Depression / diagnostic imaging
  • Depression / drug therapy
  • Depression / physiopathology
  • Female
  • Gyrus Cinguli / diagnostic imaging*
  • Gyrus Cinguli / pathology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neural Pathways / diagnostic imaging*
  • Neural Pathways / pathology
  • Prefrontal Cortex / diagnostic imaging*
  • Prefrontal Cortex / pathology
  • Recurrence
  • Secondary Prevention


  • Antidepressive Agents