Brain regulation of emotional conflict predicts antidepressant treatment response for depression

Gregory A. Fonzo, Amit Etkin, Yu Zhang, Wei Wu, Crystal Cooper, Cherise Chin-Fatt, Manish K. Jha, Joseph Trombello, Thilo Deckersbach, Phil Adams, Melvin McInnis, Patrick J. McGrath, Myrna M. Weissman, Maurizio Fava, Madhukar H. Trivedi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The efficacy of antidepressant treatment for depression is controversial due to the only modest superiority demonstrated over placebo. However, neurobiological heterogeneity within depression may limit overall antidepressant efficacy. We sought to identify a neurobiological phenotype responsive to antidepressant treatment by testing pretreatment brain activation during response to, and regulation of, emotional conflict as a moderator of the clinical benefit of the antidepressant sertraline versus placebo. Using neuroimaging data from a large randomized controlled trial, we found widespread moderation of clinical benefits by brain activity during regulation of emotional conflict, in which greater downregulation of conflict-responsive regions predicted better sertraline outcomes. Treatment-predictive machine learning using brain metrics outperformed a model trained on clinical and demographic variables. Our findings demonstrate that antidepressant response is predicted by brain activity underlying a key self-regulatory emotional capacity. Leveraging brain-based measures in psychiatry will forge a path toward better treatment personalization, refined mechanistic insights and improved outcomes.

Original languageEnglish (US)
JournalNature Human Behaviour
DOIs
StateAccepted/In press - Jan 1 2019

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Antidepressive Agents
Depression
Brain
Sertraline
Placebos
Therapeutics
Neuroimaging
Psychiatry
Down-Regulation
Randomized Controlled Trials
Demography
Conflict (Psychology)
Phenotype

ASJC Scopus subject areas

  • Social Psychology
  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience

Cite this

Brain regulation of emotional conflict predicts antidepressant treatment response for depression. / Fonzo, Gregory A.; Etkin, Amit; Zhang, Yu; Wu, Wei; Cooper, Crystal; Chin-Fatt, Cherise; Jha, Manish K.; Trombello, Joseph; Deckersbach, Thilo; Adams, Phil; McInnis, Melvin; McGrath, Patrick J.; Weissman, Myrna M.; Fava, Maurizio; Trivedi, Madhukar H.

In: Nature Human Behaviour, 01.01.2019.

Research output: Contribution to journalArticle

Fonzo, Gregory A. ; Etkin, Amit ; Zhang, Yu ; Wu, Wei ; Cooper, Crystal ; Chin-Fatt, Cherise ; Jha, Manish K. ; Trombello, Joseph ; Deckersbach, Thilo ; Adams, Phil ; McInnis, Melvin ; McGrath, Patrick J. ; Weissman, Myrna M. ; Fava, Maurizio ; Trivedi, Madhukar H. / Brain regulation of emotional conflict predicts antidepressant treatment response for depression. In: Nature Human Behaviour. 2019.
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