Ventral Striatum Response During Reward and Punishment Reversal Learning in Unmedicated Major Depressive Disorder
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OBJECTIVE: Affective biases may underlie many of the key symptoms of major depressive disorder, from anhedonia to altered cognitive performance. Understanding the cause of these biases is therefore critical in the quest for improved treatments. Depression is associated, for example, with a negative affective bias in reversal learning. However, despite the fact that reversal learning is associated with striatal response in healthy individuals and depressed individuals exhibit attenuated striatal function on multiple tasks, studies to date have not demonstrated striatal involvement in the negative bias in reversal learning in depression. In this study, the authors sought to determine whether this may be because reversal learning tasks conventionally used to study behavior examine reversals only on the basis of unexpected punishment and therefore do not adequately separate reward- and punishment-based behavior. METHOD: The authors used functional MRI to compare the hemodynamic response to a reversal learning task with mixed reward- and punishment-based reversal stages between individuals with unmedicated major depressive disorder (N=13) and healthy comparison subjects (N=14). RESULTS: Impaired reward (but not punishment) reversal accuracy was found alongside attenuated anteroventral striatal response to unexpected reward in depression. CONCLUSIONS: Attenuated neurophysiological response of the anteroventral striatum may reflect dysfunction in circuits involving afferent projections from the orbitofrontal, limbic, and/or mesostriatal dopaminergic pathways, which conceivably may, together with the ventral striatum, underlie anhedonia in depression. Learning to appreciate and enjoy positive life experiences is critical for recovery from depression. This study pinpoints a neural target for such recovery.
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Reward learning is impaired in MDD, and this impairment is correlated with the severity of anhedonic symptoms.
“Reward learning has also been found to be impaired in MDD [206], and this impairment is correlated with the severity of anhedonic symptoms [207].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [206]
Striatal activity is disrupted during reward learning, prediction-error encoding, and rewarding outcomes in MDD.
“Several studies showed a disruption of striatal activity during reward learning, prediction-error encoding, and rewarding outcomes (Table 1) (Kumar et al., 2008; Gradin et al., 2011; Robinson et al., 2012).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Robinson et al., 2012
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- Authors
- Robinson, O. J., Cools, R., Carlisi, C. O., Sahakian, B. J., & Drevets, W. C.
- Affiliations
- National Institutes of Health (US)
- Venue
- American Journal of Psychiatry
- Published
- 2012-02
- Volume
- 169
- Issue
- 2
- Pages
- 152-159
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC5648982
- OpenAlex
- W2052548944
- Cited by
- 232
- References
- 39
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 17 · 2022: 8 · 2021: 19 · 2020: 20 · 2019: 14 · 2018: 10 · 2017: 21 · 2016: 16 · 2015: 27 · 2014: 29 · 2013: 22 · 2012: 8
- FWCI
- 10.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health (Z99 MH999999)
- National Institute of Mental Health (Z01MH002792)
- 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
- major depressive disorder, ventral striatum, affective bias, anhedonia, dopaminergic pathways, orbitofrontal cortex, untreated depression
- MeSH terms
- Basal Ganglia, Behavioral Symptoms, Cognition, Major Depressive Disorder, Humans, Magnetic Resonance Imaging, Psychophysiology, Punishment, Reaction Time, Reversal Learning, Reward, Task Performance and Analysis, Anhedonia, Functional Neuroimaging
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