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 language | English (US) |
|---|---|
| Journal | Molecular Psychiatry |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
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ASJC Scopus subject areas
- Molecular Biology
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
Cite this
Reward related ventral striatal activity and differential response to sertraline versus placebo in depressed individuals. / Greenberg, Tsafrir; Fournier, Jay C.; Stiffler, Richelle; Chase, Henry W.; Almeida, Jorge R.; Aslam, Haris; Deckersbach, Thilo; Cooper Cortes, Crystal; Toups, Marisa; Carmody, Thomas J; Kurian, Benji; Peltier, Scott; Adams, Phillip; McInnis, Melvin G.; Oquendo, Maria A.; Fava, Maurizio; Parsey, Ramin; McGrath, Patrick J.; Weissman, Myrna; Trivedi, Madhukar H; Phillips, Mary L.
In: Molecular Psychiatry, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reward related ventral striatal activity and differential response to sertraline versus placebo in depressed individuals
AU - Greenberg, Tsafrir
AU - Fournier, Jay C.
AU - Stiffler, Richelle
AU - Chase, Henry W.
AU - Almeida, Jorge R.
AU - Aslam, Haris
AU - Deckersbach, Thilo
AU - Cooper Cortes, Crystal
AU - Toups, Marisa
AU - Carmody, Thomas J
AU - Kurian, Benji
AU - Peltier, Scott
AU - Adams, Phillip
AU - McInnis, Melvin G.
AU - Oquendo, Maria A.
AU - Fava, Maurizio
AU - Parsey, Ramin
AU - McGrath, Patrick J.
AU - Weissman, Myrna
AU - Trivedi, Madhukar H
AU - Phillips, Mary L.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85071945722&partnerID=8YFLogxK
U2 - 10.1038/s41380-019-0490-5
DO - 10.1038/s41380-019-0490-5
M3 - Article
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
ER -