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

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.

SUBMITTER: Berwian I

PROVIDER: S-EPMC7749105 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:ImportanceMajor depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships.ObjectiveTo examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions.Design, setting, and participantsA cross-sectional resting-state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses.Main outcomes and measuresUsing a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level-dependent signal of each voxel in the whole brain with that of the amygdala.ResultsAdolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this connectivity was inversely correlated with general depression (R = -.523, P = .01), dysphoria (R = -.455, P = .05), and lassitude (R = -.449, P = .05) and was positively correlated with well-being (R = .470, P = .03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P < .05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving as controls.Conclusions and relevanceImpaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression.

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

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