Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression
Open accessAbstract
Unipolar and bipolar depressive episodes have a similar clinical presentation that suggests common dysfunction of the brain's reward system. Here, we evaluated the relationship of both dimensional depression severity and diagnostic category to reward system function in both bipolar and unipolar depression. In total, 89 adults were included, including 27 with bipolar depression, 25 with unipolar depression, and 37 healthy comparison subjects. Subjects completed both a monetary reward task and a resting-state acquisition during 3T BOLD fMRI. Across disorders, depression severity was significantly associated with reduced activation for wins compared with losses in bilateral ventral striatum, anterior cingulate cortex, posterior cingulate cortex, and right anterior insula. Resting-state connectivity within this reward network was also diminished in proportion to depression severity, most notably connectivity strength in the left ventral striatum. In addition, there were categorical differences between patient groups: resting-state connectivity at multiple reward network nodes was higher in bipolar than in unipolar depression. Reduced reward system task activation and resting-state connectivity therefore appear to be a brain phenotype that is dimensionally related to depression severity in both bipolar and unipolar depression. In contrast, categorical differences in reward system resting connectivity between unipolar and bipolar depression may reflect differential risk of mania. Reward system dysfunction thus represents a common brain mechanism with relevance that spans categories of psychiatric diagnosis.
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A large scale trans-diagnostic voxel-based morphometry meta-analysis suggested that the hippocampus might be selectively affected in MDD compared to other psychiatric disorders such as schizophrenia, bipolar disorder, addiction, obsessive-compulsive disorder, and anxiety.
“Furthermore, a large scale trans-diagnostic voxel-based morphometry meta-analysis of 193 studies comprising 15,892 individuals also suggested that the hippocampus might be selectively affected in MDD compared to other psychiatric disorders such as schizophrenia, bipolar disorder, addiction, obsessive-compulsive disorder, and anxiety 97 .”
From Major depressive disorder (2016) · cites this paper as [97]
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- Authors
- Satterthwaite, T. D., Kable, J. W., Vandekar, L., Katchmar, N., Bassett, D. S., Baldassano, C. F., Ruparel, K., Elliott, M. A., Sheline, Y. I., Gur, R. C., Gur, R. E., Davatzikos, C., Leibenluft, E., Thase, M. E., & Wolf, D. H.
- Affiliations
- University of Pennsylvania (US)
- National Institutes of Health (US)
- Corresponding author
- Satterthwaite, Theodore D
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2015-03-13
- Volume
- 40
- Issue
- 9
- Pages
- 2258-2268
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4613620
- OpenAlex
- W2110508899
- Semantic Scholar
- efe99a44ff634a2c72570dff1f8c38f630909a71
- Cited by
- 249
- References
- 61
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 20 · 2023: 25 · 2022: 27 · 2021: 47 · 2020: 21 · 2019: 20 · 2018: 26 · 2017: 14 · 2016: 15 · 2015: 5
- FWCI
- 16.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sidney R. Baer, Jr. Foundation
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- American Psychiatric Institute for Research and Education
- University of Pennsylvania
- Sunovion
- Cerecor
- University of Pennsylvania Health System
- H. Lundbeck A/S
- National Institute of Mental Health (K23MH085096, K23MH098130, R01MH101111, MH019112, T32MH019112)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- reward system dysfunction, bipolar depression, major depressive disorder, depression severity, ventral striatum, resting-state functional connectivity, anterior cingulate cortex, posterior cingulate cortex, anterior insula, brain phenotypes
- MeSH terms
- Adult, Bipolar Disorder, Brain, Depression, Dissociative Disorders, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Oxygen, Psychiatric Status Rating Scales, Rest, Reward
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