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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 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 and Phillips ML.
American Journal of Psychiatry, 172:881-891, 2015

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.  Investigators in the Department of Psychiatry’s Mood and Brain Laboratory 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.

Led by Drs. Tsafrir Greenberg, Henry Chase, and their mentor, Dr. Mary Phillips, the investigators recruited 148 unmedicated individuals with major depressive disorder and 31 healthy comparison individuals for the multisite Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study.  Participants underwent functional MRI during a well-validated reward task. Dr. Greenberg and his colleagues examined the region of interest and whole-brain data in the first- (N=78) and second- (N=70) recruited cohorts, as well as the total sample of depressed individuals, and in healthy individuals.

Findings from this study indicate that 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.  The investigators concluded that 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. These results suggest reduced reward-contingency learning with greater anhedonia.

Findings from this project will help investigators elucidate neural mechanisms of anhedonia and take the next step in terms of identifying potential biosignatures of treatment response.

Contributors:  
Tsafrir Greenberg, PhD, Henry W. Chase, PhD, Mary L. Phillips, MD, MD (Cantab), Richelle Stiffler, MSW, Carlos R. Zevallos, BA and Haris A. Aslam, BS (Department of Psychiatry, University of Pittsburgh School of Medicine)

Jorge R. Almeida, MD, PhD (Department of Psychiatry, Brown University)

Thilo Deckersbach, PhD (Department of Psychiatry, Massachusetts General Hospital)

Sarah Weyandt, PhD, Crystal Cooper, PhD, Marisa Toups, MD, Thomas Carmody, PhD, Benji Kurian, MD and Madhukar H. Trivedi, MD (Department of Psychiatry, University of Texas Southwestern Medical Center)

Scott Peltier, PhD and Melvin G. McInnis, MD (Department of Psychiatry, University of Michigan)

Maurizio Fava, MD (Department of Psychiatry, Harvard University)

Phillip Adams, PhD, Maria A. Oquendo, MD, Patrick J. McGrath, MD and Myrna Weissman, PhD (Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute)

Ramin Parsey, MD, PhD (Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University)

This article appears in the American Journal of Psychiatry.  To view the abstract, click here.