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
Open accessAbstract
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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Disruption of inverse correlation between reward expectancy and prediction error reactivity in VS is associated with anhedonia severity in both HCs and MDD.
“This disruption was associated with anhedonia severity both in HCs and MDD patients.”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Greenberg et al., 2015
Unmedicated MDD patients show disruption of inverse correlation between reward expectancy and prediction error-associated reactivity in VS, found in healthy volunteers.
“In line with these results, an fMRI study in a large sample of unmedicated MDD patients showed that depressed patients show a disruption of the inverse correlation between reward expectancy and prediction error-associated reactivity in the VS, which is found in healthy volunteers (Greenberg et al., 2015).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Greenberg et al., 2015
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References 31 · Cited by 93
Research works printed but not linked: 3
- [22]First MB Spitzer RL Gibbon M Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P) 2002 New York Biometrics Research, New York State Psychiatric Institute
- [27]Spielberger CD Gorsuch RL Lushene RE Manualfor the State-Trait Anxiety Inventory (form Y) 1983 Palo Alto, Calif Consulting Psychologists Press
- [32]Pavlov IP Conditioned reflexes 1927 London Oxford University Press
- Authors
- Greenberg, T., Chase, H. W., Almeida, J. R., Stiffler, R., Zevallos, C. R., Aslam, H. A., Deckersbach, T., Weyandt, S., Cooper, C., Toups, M., Carmody, T., Kurian, B., Peltier, S., Adams, P., McInnis, M. G., Oquendo, M. A., McGrath, P. J., Fava, M., Weissman, M., Parsey, R., Trivedi, M. H., & Phillips, M. L.
- Affiliations
- University of Pittsburgh (US)
- From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of...
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2015-09-01
- Volume
- 172
- Issue
- 9
- Pages
- 881-891
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC4858169
- OpenAlex
- W1913304673
- Cited by
- 93
- References
- 31
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 12 · 2020: 14 · 2019: 13 · 2018: 8 · 2017: 7 · 2016: 9 · 2015: 3
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- National Institute of Mental Health (R25MH101076, U01MH092250, U01MH092221)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- anhedonia, major depressive disorder, reward expectancy, prediction error, ventral striatum, reward processing, untreated depression
- MeSH terms
- Adult, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Psychiatric Status Rating Scales, Reward, Case-Control Studies, Anticipation, Psychological, Anhedonia, Functional Neuroimaging, Ventral Striatum
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