Moderation of the relationship between reward expectancy and prediction error-related ventral striatal reactivity by anhedonia in unmedicated major depressive disorder: Findings from the EMBARC study

Tsafrir Greenberg, Henry W. Chase, Jorge R. Almeida, Richelle Stiffler, Carlos R. Zevallos, Haris A. Aslam, Thilo Deckersbach, Sarah Weyandt, Crystal Cooper, Marisa Toups, Thomas Carmody, Benji Kurian, Scott Peltier, Phillip Adams, Melvin G. McInnis, Maria A. Oquendo, Patrick J. McGrath, Maurizio Fava, Myrna Weissman, Ramin ParseyMadhukar H. Trivedi, Mary L. Phillips

Research output: Contribution to journalArticle

Abstract

Objective: Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected outcome value) and prediction error-(discrepancy between expected and actual outcome) related ventral striatal reactivity, as well as the relationship between these measures. Method: A total of 148 unmedicated individuals with major depressive disorder and 31 healthy comparison individuals recruited for the multisite EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study underwent functional MRI during a well-validated reward task. Region of interest and whole-brain data were examined in the first- (N=78) and second- (N=70) recruited cohorts, as well as the total sample, of depressed individuals, and in healthy individuals. Results: Healthy, but not depressed, individuals showed a significant inverse relationship between reward expectancy and prediction error-related right ventral striatal reactivity. Across all participants, and in depressed individuals only, greater anhedonia severity was associated with a reduced reward expectancy-prediction error inverse relationship, even after controlling for other symptoms. Conclusions: The normal reward expectancy and prediction error-related ventral striatal reactivity inverse relationship concords with conditioning models, predicting a shift in ventral striatal responding from reward outcomes to reward cues. This study shows, for the first time, an absence of this relationship in two cohorts of unmedicated depressed individuals and a moderation of this relationship by anhedonia, suggesting reduced reward-contingency learning with greater anhedonia. These findings help elucidate neural mechanisms of anhedonia, as a step toward identifying potential biosignatures of treatment response.

Original languageEnglish (US)
Pages (from-to)881-891
Number of pages11
JournalAmerican Journal of Psychiatry
Volume172
Issue number9
DOIs
StatePublished - Sep 1 2015
Externally publishedYes

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Anhedonia
Corpus Striatum
Major Depressive Disorder
Reward
Antidepressive Agents
Clinical Studies
Prediction
Expectancy
Reactivity
Antidepressants
Moderation
Cues
Magnetic Resonance Imaging
Learning

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Arts and Humanities (miscellaneous)
  • Medicine(all)

Cite this

Moderation of the relationship between reward expectancy and prediction error-related ventral striatal reactivity by anhedonia in unmedicated major depressive disorder : Findings from the EMBARC study. / Greenberg, Tsafrir; Chase, Henry W.; Almeida, Jorge R.; Stiffler, Richelle; Zevallos, Carlos R.; Aslam, Haris A.; Deckersbach, Thilo; Weyandt, Sarah; Cooper, Crystal; Toups, Marisa; Carmody, Thomas; Kurian, Benji; Peltier, Scott; Adams, Phillip; McInnis, Melvin G.; Oquendo, Maria A.; McGrath, Patrick J.; Fava, Maurizio; Weissman, Myrna; Parsey, Ramin; Trivedi, Madhukar H.; Phillips, Mary L.

In: American Journal of Psychiatry, Vol. 172, No. 9, 01.09.2015, p. 881-891.

Research output: Contribution to journalArticle

Greenberg, T, Chase, HW, Almeida, JR, Stiffler, R, Zevallos, CR, Aslam, HA, Deckersbach, T, Weyandt, S, Cooper, C, Toups, M, Carmody, T, Kurian, B, Peltier, S, Adams, P, McInnis, MG, Oquendo, MA, McGrath, PJ, Fava, M, Weissman, M, Parsey, R, Trivedi, MH & Phillips, ML 2015, 'Moderation of the relationship between reward expectancy and prediction error-related ventral striatal reactivity by anhedonia in unmedicated major depressive disorder: Findings from the EMBARC study', American Journal of Psychiatry, vol. 172, no. 9, pp. 881-891. https://doi.org/10.1176/appi.ajp.2015.14050594
Greenberg, Tsafrir ; Chase, Henry W. ; Almeida, Jorge R. ; Stiffler, Richelle ; Zevallos, Carlos R. ; Aslam, Haris A. ; Deckersbach, Thilo ; Weyandt, Sarah ; Cooper, Crystal ; Toups, Marisa ; Carmody, Thomas ; Kurian, Benji ; Peltier, Scott ; Adams, Phillip ; McInnis, Melvin G. ; Oquendo, Maria A. ; McGrath, Patrick J. ; Fava, Maurizio ; Weissman, Myrna ; Parsey, Ramin ; Trivedi, Madhukar H. ; Phillips, Mary L. / Moderation of the relationship between reward expectancy and prediction error-related ventral striatal reactivity by anhedonia in unmedicated major depressive disorder : Findings from the EMBARC study. In: American Journal of Psychiatry. 2015 ; Vol. 172, No. 9. pp. 881-891.
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AU - Greenberg, Tsafrir

AU - Chase, Henry W.

AU - Almeida, Jorge R.

AU - Stiffler, Richelle

AU - Zevallos, Carlos R.

AU - Aslam, Haris A.

AU - Deckersbach, Thilo

AU - Weyandt, Sarah

AU - Cooper, Crystal

AU - Toups, Marisa

AU - Carmody, Thomas

AU - Kurian, Benji

AU - Peltier, Scott

AU - Adams, Phillip

AU - McInnis, Melvin G.

AU - Oquendo, Maria A.

AU - McGrath, Patrick J.

AU - Fava, Maurizio

AU - Weissman, Myrna

AU - Parsey, Ramin

AU - Trivedi, Madhukar H.

AU - Phillips, Mary L.

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N2 - Objective: Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected outcome value) and prediction error-(discrepancy between expected and actual outcome) related ventral striatal reactivity, as well as the relationship between these measures. Method: A total of 148 unmedicated individuals with major depressive disorder and 31 healthy comparison individuals recruited for the multisite EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study underwent functional MRI during a well-validated reward task. Region of interest and whole-brain data were examined in the first- (N=78) and second- (N=70) recruited cohorts, as well as the total sample, of depressed individuals, and in healthy individuals. Results: Healthy, but not depressed, individuals showed a significant inverse relationship between reward expectancy and prediction error-related right ventral striatal reactivity. Across all participants, and in depressed individuals only, greater anhedonia severity was associated with a reduced reward expectancy-prediction error inverse relationship, even after controlling for other symptoms. Conclusions: The normal reward expectancy and prediction error-related ventral striatal reactivity inverse relationship concords with conditioning models, predicting a shift in ventral striatal responding from reward outcomes to reward cues. This study shows, for the first time, an absence of this relationship in two cohorts of unmedicated depressed individuals and a moderation of this relationship by anhedonia, suggesting reduced reward-contingency learning with greater anhedonia. These findings help elucidate neural mechanisms of anhedonia, as a step toward identifying potential biosignatures of treatment response.

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