Reward related ventral striatal activity and differential response to sertraline versus placebo in depressed individuals

Tsafrir Greenberg, Jay C. Fournier, Richelle Stiffler, Henry W. Chase, Jorge R. Almeida, Haris Aslam, Thilo Deckersbach, Crystal Cooper, Marisa S. Toups, Tom Carmody, Benji Kurian, Scott Peltier, Phillip Adams, Melvin G. McInnis, Maria A. Oquendo, Maurizio Fava, Ramin Parsey, Patrick J. McGrath, Myrna Weissman, Madhukar TrivediMary L. Phillips

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Medications to treat major depressive disorder (MDD) are not equally effective across patients. Given that neural response to rewards is altered in MDD and given that reward-related circuitry is modulated by dopamine and serotonin, we examined, for the first time, whether reward-related neural activity moderated response to sertraline, an antidepressant medication that targets these neurotransmitters. A total of 222 unmedicated adults with MDD randomized to receive sertraline (n = 110) or placebo (n = 112) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study completed demographic and clinical assessments, and pretreatment functional magnetic resonance imaging while performing a reward task. We tested whether an index of reward system function in the ventral striatum (VS), a key reward circuitry region, moderated differential response to sertraline versus placebo, assessed with the Hamilton Rating Scale for Depression (HSRD) over 8 weeks. We observed a significant moderation effect of the reward index, reflecting the temporal dynamics of VS activity, on week-8 depression levels (Fs ≥ 9.67, ps ≤ 0.002). Specifically, VS responses that were abnormal with respect to predictions from reinforcement learning theory were associated with lower week-8 depression symptoms in the sertraline versus placebo arms. Thus, a more abnormal pattern of pretreatment VS dynamic response to reward expectancy (expected outcome value) and prediction error (difference between expected and actual outcome), likely reflecting serotonergic and dopaminergic deficits, was associated with better response to sertraline than placebo. Pretreatment measures of reward-related VS activity may serve as objective neural markers to advance efforts to personalize interventions by guiding individual-level choice of antidepressant treatment.

Original languageEnglish (US)
Pages (from-to)1526-1536
Number of pages11
JournalMolecular psychiatry
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Greenberg, T., Fournier, J. C., Stiffler, R., Chase, H. W., Almeida, J. R., Aslam, H., Deckersbach, T., Cooper, C., Toups, M. S., Carmody, T., Kurian, B., Peltier, S., Adams, P., McInnis, M. G., Oquendo, M. A., Fava, M., Parsey, R., McGrath, P. J., Weissman, M., ... Phillips, M. L. (2020). Reward related ventral striatal activity and differential response to sertraline versus placebo in depressed individuals. Molecular psychiatry, 25(7), 1526-1536. https://doi.org/10.1038/s41380-019-0490-5