Cited by 89Neurotransmitter Receptor Influence on BehaviorTreatment of Major DepressionTryptophan and brain disorders

Influences of dopaminergic system dysfunction on late-life depression

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Taylor, Warren D., Zald, David H., Felger, Jennifer C., Christman, Seth, Claassen, Daniel O., Horga, Guillermo, Miller, Jeffrey M., Gifford, Katherine +3 more·2022·Molecular Psychiatry

Abstract

Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflammatory burden, the role of dopamine may be particularly salient for late-life depression. We review the literature examining the role of dopamine in the pathogenesis of depression, as well as how dopamine function changes with aging and is influenced by inflammation. Applying a Research Domain Criteria (RDoC) Initiative perspective, we then review work examining how dopaminergic signaling affects these domains, specifically focusing on Cognitive, Positive Valence, and Sensorimotor Systems. We propose a unified model incorporating the effects of aging and low-grade inflammation on dopaminergic functioning, with a resulting negative effect on cognition, reward processing, and motor function. Interplay between these systems may influence development of a depressive phenotype, with an initial deficit in one domain reinforcing decline in others. This model extends RDoC concepts into late-life depression while also providing opportunities for novel and personalized interventions.

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  1. [147]Devine ST, Otto AR, Bolenz F, Reiter AM, Eppinger B. Cognitive resource limitations shift effort trade-offs across the lifespan. PsyArXiv 2019.

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Authors
Taylor, W. D., Zald, D. H., Felger, J. C., Christman, S., Claassen, D. O., Horga, G., Miller, J. M., Gifford, K., Rogers, B., Szymkowicz, S. M., & Rutherford, B. R.
Affiliations
  • VA Tennessee Valley Healthcare System (US)
  • Rutgers, The State University of New Jersey (US)
  • Emory University (US)
  • Vanderbilt University Medical Center (US)
  • New York State Psychiatric Institute (US)
Corresponding author
Taylor, Warren D.
Venue
Molecular Psychiatry
Published
2021-08-17
Volume
27
Issue
1
Pages
180-191
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
OpenAlex
W3195142114
Cited by
89
References
232
Citations by year
2026: 18 · 2025: 23 · 2024: 14 · 2023: 24 · 2022: 9 · 2021: 1
FWCI
1.81
Type
journal article
Language
en
Open access
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (K24 MH110598, R01 MH123662, R01 MH123660)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
geriatric depression, dopaminergic dysfunction, dopamine, aging, low-grade inflammation, cognitive impairment, reward processing, motor function, Research Domain Criteria, positive valence systems, sensorimotor system, cognitive systems, personalized interventions
MeSH terms
Cognition, Depression, Dopamine, Reward

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