The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders
Open accessAbstract
Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological, and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions. Supporting the dopamine imbalance hypothesis, structural and functional neuroimaging studies show abnormalities in the frontal and striatal regions that are heavily innervated by dopamine neurons. Further, dopaminergic psychostimulant medication has been shown to alleviate fatigue in individuals with traumatic brain injury, chronic fatigue syndrome, and in cancer patients, also indicating that dopamine might play an important role in fatigue perception. This paper reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest that dopamine plays a critical role in the phenomenon of fatigue. We conclude with how specific aspects of the dopamine imbalance hypothesis can be tested in future research.
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Fatigue is associated with alterations in dopamine and associated frontostriatal regions.
“At the neural level, fatigue is associated with alterations in dopamine and associated frontostriatal regions (Dobryakova et al., 2015).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Dobryakova et al., 2015
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Dooley, L. N., Kuhlman, K. R., Robles, T. F., Eisenberger, N. I., Craske, M. G., & Bower, J. E. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.006 · Cited by 176 · see citing works
- Authors
- Dobryakova, E., Genova, H. M., DeLuca, J., & Wylie, G. R.
- Affiliations
- Kessler Foundation (US)
- United States Department of Veterans Affairs (US)
- Corresponding author
- Dobryakova, Ekaterina
- Venue
- Frontiers in Neurology
- Publisher
- Frontiers Media SA
- Published
- 2015-03-12
- Volume
- 6
- Pages
- 52-52
- ISSN
- 1664-2295 (ISSN-L)
- PMC
- PMC4357260
- OpenAlex
- W1973717649
- Cited by
- 242
- References
- 95
- Citations by year
- 2026: 22 · 2025: 23 · 2024: 21 · 2023: 21 · 2022: 27 · 2021: 33 · 2020: 16 · 2019: 25 · 2018: 14 · 2017: 20 · 2016: 16 · 2015: 4
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neurology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Keywords
- fatigue, multiple sclerosis, striatum, prefrontal cortex, dopamine signaling, traumatic brain injury, chronic fatigue syndrome, cancer-related fatigue, fatigue perception
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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