Remitted major depression is characterized by reward network hyperactivation during reward anticipation and hypoactivation during reward outcomes
Open accessAbstract
Background Although functional brain imaging has established that individuals with unipolar major depressive disorder (MDD) are characterized by frontostriatal dysfunction during reward processing, no research to date has examined the chronometry of neural responses to rewards in euthymic individuals with a history of MDD.Method A monetary incentive delay task was used during fMRI scanning to assess neural responses in frontostriatal reward regions during reward anticipation and outcomes in 19 participants with remitted major depressive disorder (rMDD) and in 19 matched control participants.Results During the anticipation phase of the task, the rMDD group was characterized by relatively greater activation in bilateral anterior cingulate gyrus, in right midfrontal gyrus, and in the right cerebellum. During the outcome phase of the task, the rMDD group was characterized by relatively decreased activation in bilateral orbital frontal cortex, right frontal pole, left insular cortex, and left thalamus. Exploratory analyses indicated that activation within a right frontal pole cluster that differentiated groups during reward anticipation predicted the number of lifetime depressive episodes within the rMDD group.Limitations Replication with larger samples is needed.Conclusions Results suggest a double dissociation between reward network reactivity and temporal phase of the reward response in rMDD, such that rMDD is generally characterized by reward network hyperactivation during reward anticipation and reward network hypoactivation during reward outcomes. More broadly, these data suggest that aberrant frontostriatal response to rewards may potentially represent a trait marker for MDD, though future research is needed to evaluate the prospective utility of this functional neural endophenotype as a marker of MDD risk.
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Although some abnormalities persist after remission, including orbitofrontal cortex hypo-responses to rewards and inability to sustain ventral striatal responses to positive cues, acute striatal responses to rewards appear to normalize in individuals with past major depressive disorder.
“Finally, although some abnormalities persist after remission (e.g., OFC hypo-responses to rewards [107], inability to sustain ventral striatal responses to positive cues [108]), acute striatal responses to rewards appear to normalize in individuals with past MDD [109].”
From Prefrontal cortex and depression (2022) · cites this paper as [107]
Individuals with remitted unipolar MDD show reward-network hyperactivation during reward anticipation and hypoactivation during reward outcomes.
“Dichter and colleagues [236] reported reward-network hyperactivation during reward anticipation and hypoactivation during reward outcomes in individuals with remitted unipolar MDD.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [236]
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References 72 · Cited by 170
Research works printed but not linked: 2
- Forbes EE Christopher May J Siegle GJ Ladouceur CD Ryan ND Carter CS Birmaher B Axelson DA Dahl RE 2006b Reward-related decision-making in pediatric major depressive disorder: an fMRI study J Child Psychol Psychiatry 47 10 1031 1040 17073982 PMC2129133
- Forbes EE Hariri AR Martin SL Silk JS Moyles DL Fisher PM Brown SM Ryan ND Birmaher B Axelson DA Dahl RE 2009 Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder Am J Psychiatry 166 1 64 73 19047324 PMC2701209
- Authors
- Dichter, G. S., Kozink, R. V., McClernon, F. J., & Smoski, M. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Duke Medical Center (US)
- Corresponding author
- Dichter, Gabriel S.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 136
- Issue
- 3
- Pages
- 1126-1134
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC3272083
- OpenAlex
- W1998733397
- Cited by
- 170
- References
- 72
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 5 · 2023: 10 · 2022: 13 · 2021: 15 · 2020: 10 · 2019: 11 · 2018: 10 · 2017: 13 · 2016: 15 · 2015: 22 · 2014: 7 · 2013: 11 · 2012: 5
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K23MH087754, R03MH078145, K23MH081285)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30-HD03110, P30HD003110)
- 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
- remitted depression, reward processing, reward anticipation, reward outcome, frontostriatal dysfunction, anterior cingulate cortex, frontal pole, orbitofrontal cortex, cerebellum, thalamus, insula, monetary incentive delay task, trait markers
- MeSH terms
- Adult, Brain, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Motivation, Prospective Studies, Reward, Young Adult, Anticipation, Psychological
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