Dorsolateral Prefrontal Cortex and Subcallosal Cingulate Connectivity Show Preferential Antidepressant Response in Major Depressive Disorder

Cherise Regina Chin Fatt, Crystal Cooper, Manish K Jha, Sina Aslan, Bruce D Grannemann, Benji Kurian, Tracy L. Greer, Maurizio Fava, Myrna Weissman, Patrick J. McGrath, Ramin V. Parsey, Amit Etkin, Mary L. Phillips, Madhukar H. Trivedi

Research output: Contribution to journalArticle

Abstract

Background: Major depressive disorder is associated with abnormal connectivity across emotion and reward circuits as well as other established circuits that may negatively impact treatment response. The goal of this study was to perform an exploratory reanalysis of archival data from a clinical trial to identify moderators of treatment outcome of sertraline over placebo. Methods: EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study participants completed magnetic resonance imaging before randomization to either sertraline or placebo for 8 weeks (n = 279). Seed-based functional connectivity was computed using 4 bilateral seeds (2 spheres defined bilaterally): amygdala, dorsolateral prefrontal cortex (DLPFC), subcallosal cingulate cortex, and ventral striatum. Functional connectivity maps were generated, principal component analysis was performed, linear mixed effects models were used to determine moderators of treatment outcome, and post hoc analyses were used to determine level of connectivity (low and high, −1 and +1 SD from the mean) that was most sensitive to improved depression severity (baseline to week 8) based on treatment. Results: Greater mean reduction in the 17-item Hamilton Rating Scale for Depression score by 8 weeks occurred with sertraline relative to placebo when connectivity in the DLPFC was low (3-way interaction test, p =.05). Conditional on low connectivity in the DLPFC and subcallosal cingulate cortex and high connectivity in the ventral striatum and amygdala, there was on average a 4.8-point greater reduction in the 17-item Hamilton Rating Scale for Depression score with sertraline relative to placebo (p =.003). Conclusions: The level of functional connectivity seeded in both the DLPFC and the subcallosal cingulate cortex networks may play an important role in identifying a favorable response to sertraline over placebo.

Original languageEnglish (US)
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
DOIs
StateAccepted/In press - 2020

Keywords

  • Amygdala
  • Antidepressant response
  • Central executive network
  • Depression
  • Dorsolateral prefrontal cortex
  • EMBARC
  • fcMRI
  • Functional connectivity
  • NCT01407094
  • Resting state
  • Subcallosal cingulate
  • Ventral striatum

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cognitive Neuroscience
  • Clinical Neurology
  • Biological Psychiatry

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