Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder
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Objective: Rational therapeutic development in bipolar is hampered by a lack of pathophysiological model. However, there is a wealth of converging data on the role of dopamine in bipolar disorder. This paper therefore examines the possibility of a dopamine hypothesis for bipolar disorder. Method: A literature search was conducted using standard search engines Embase, PyschLIT, PubMed and MEDLINE. In addition, papers and book chapters known to the authors were retrieved and examined for further relevant articles. Results: Collectively, in excess of 100 articles were reviewed from which approximately 75% were relevant to the focus of this paper. Conclusion: Pharmacological models suggest a role of increased dopaminergic drive in mania and the converse in depression. In Parkinson’s disease, administration of high‐dose dopamine precursors can produce a ‘maniform’ picture, which switches into a depressive analogue on withdrawal. It is possible that in bipolar disorder there is a cyclical process, where increased dopaminergic transmission in mania leads to a secondary down regulation of dopaminergic receptor sensitivity over time. This may lead to a period of decreased dopaminergic transmission, corresponding with the depressive phase, and the repetition of the cycle. This model, if verified, may have implications for rational drug development.
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The manic/hypomanic phase is associated with elevated dopamine levels.
“The manic/hypomanic phase is associated with elevated dopamine levels (Berk et al., 2007).”
From A motivation model of sex addiction – Relevance to the controversy over the concept (2022) · cites this paper as Berk et al., 2007
In bipolar disorder, oxidative stress to lipid structures could increase in a stage-dependent manner, disregarding the mood episode.
“in BD, the oxidative stress to lipid structures could actually increase in a stage-dependent manner, disregarding the mood episode [147, 148].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [148]
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McEachin, R. C., Saccone, N. L., Saccone, S. F., Kleyman-Smith, Y. D., Kar, T., Kare, R. K., Ade, A. S., Sartor, M. A., Cavalcoli, J. D., & McInnis, M. G. (2010) · BMC Medical Genetics · doi:10.1186/1471-2350-11-14 · Cited by 31 · see citing works
A motivation model of sex addiction – Relevance to the controversy over the concept
Toates, F. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104872 · Cited by 25 · see citing works
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Moon, E., Choe, B.-M., Park, J.-M., Chung, Y. I., Lee, B. D., Park, J.-H., Lee, Y. M., Jeong, H. J., Cheon, Y., Choi, Y., et al. (2018) · Psychiatry Investigation · doi:10.30773/pi.2018.05.23 · Cited by 8 · see citing works
- Authors
- Berk, M., Dodd, S., Kauer‐Sant’Anna, M., Malhi, G. S., Bourin, M., Kapczinski, F., & Norman, T.
- Affiliations
- Barwon Health (AU)
- University of British Columbia (CA)
- The University of Sydney (AU)
- Université de Nantes (FR)
- Hospital de Clínicas de Porto Alegre (BR)
- The University of Melbourne (AU)
- Corresponding author
- Berk, M.
- Venue
- Acta Psychiatrica Scandinavica
- Publisher
- Wiley
- Published
- 2007-08-07
- Volume
- 116
- Issue
- s434
- Pages
- 41-49
- ISSN
- 0001-690X (ISSN-L)
- 1600-0447
- OpenAlex
- W2138730565
- Cited by
- 396
- References
- 75
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 21 · 2023: 16 · 2022: 22 · 2021: 19 · 2020: 20 · 2019: 24 · 2018: 19 · 2017: 21 · 2016: 26 · 2015: 32 · 2014: 24 · 2013: 20 · 2012: 27
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- Acta Psychiatrica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Eli Lilly and Company
- Geelong Region Medical Research Foundation
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Fondation pour la Recherche Médicale
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Cilag
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- dopamine dysregulation syndrome, bipolar disorder, dopamine hypothesis, mania, depression, Parkinson's disease, dopamine precursor, pathophysiology, drug development
- MeSH terms
- Affect, Bipolar Disorder, Dopamine, Dose-Response Relationship, Drug, Humans, Synaptic Transmission, Parkinson Disease, Substance Withdrawal Syndrome, Dopamine Agents, Tomography, Emission-Computed, Single-Photon, Positron-Emission Tomography
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