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Influences of dopaminergic system dysfunction on late-life depression

Molecular Psychiatry volume 27, pages 180–191 (2022)Cite this article

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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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Fig. 1: Dopaminergic circuit anatomy.
Fig. 2: Model of dopaminergic system contributions and interactions to behavior in late-life depression.

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Acknowledgements

This research was supported by National Institute of Health grants K24 MH110598, R01 MH123660 and R01 MH123662. WDT would additionally like to acknowledge salary support from the Tennessee Valley Healthcare System Geriatric Research Education and Clinical Center (GRECC).

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA

    Warren D. Taylor, Seth Christman & Sarah M. Szymkowicz

  2. Geriatric Research, Education, and Clinical Center, Veterans Affairs Tennessee Valley Health System, Nashville, TN, USA

    Warren D. Taylor

  3. Department of Psychiatry Rutgers Biomedical and Health Sciences, Rutgers University, Piscataway, NJ, USA

    David H. Zald

  4. Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA

    Jennifer C. Felger

  5. Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA

    Daniel O. Claassen & Katherine Gifford

  6. Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA

    Guillermo Horga, Jeffrey M. Miller & Bret R. Rutherford

  7. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA

    Baxter Rogers

Authors
  1. Warren D. Taylor
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  2. David H. Zald
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  3. Jennifer C. Felger
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  4. Seth Christman
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  5. Daniel O. Claassen
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  6. Guillermo Horga
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  7. Jeffrey M. Miller
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  8. Katherine Gifford
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  9. Baxter Rogers
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  10. Sarah M. Szymkowicz
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  11. Bret R. Rutherford
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Contributions

WDT, DHZ, JCF, SC, SMS and BRR drafted the manuscript, while WDT, DHZ, JCF, DOC, GH, JMM, KG, BRR contributed to the conceptualization, scientific model, integration of past literature, and critical revisions of the intellectual content. All authors approved the manuscript, with WDT, DHZ and BRR providing final approval for the published version.

Corresponding author

Correspondence to Warren D. Taylor.

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Taylor, W.D., Zald, D.H., Felger, J.C. et al. Influences of dopaminergic system dysfunction on late-life depression. Mol Psychiatry 27, 180–191 (2022). https://doi.org/10.1038/s41380-021-01265-0

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  • DOI: https://doi.org/10.1038/s41380-021-01265-0

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