Novel neuroimmunologic therapeutics in depression: A clinical perspective on what we know so far
Open accessAbstract
Depression, one of the most common mental health disorders, is among the leading causes of health-related disability worldwide. Although antidepressant treatment has been available for decades, depression remains largely refractory to the prevailing limited treatment approach of monoamine transmission modulation. Fortunately, recent evidence points to a link between depression and inflammatory factors within the innate and the adaptive immune system. The purpose of this review is to evaluate current and potential clinical immunotherapies for depression, as contextually focused by an immunologic lens of the pathophysiologic mechanisms of depression. The utility of pro-inflammatory cytokines (primarily interleukin-1β, interleukin -6 and tumor necrosis factor-α) is considered in their role as screening biomarkers in prediction of treatment response or nonresponse. The evidence base of numerous recent clinical studies is discussed as related to their antidepressant efficacy and favorable safety profile, with consideration of multiple agents that target inflammatory mechanisms linked to depression including nonsteroidal anti-inflammatory pathways (i.e., aspirin, celecoxib), cytokine antagonism (i.e., etanercept, infliximab), N-methyl-D-aspartate receptor (NMDA) receptor antagonism (i.e., ketamine), and modulation of kynurenine pathways (i.e., minocycline). Additionally, new and exciting directions in targeting inflammatory mechanisms in the treatment of depression are underway, and future investigation is also warranted to explore the utility of inflammation in diagnosing depression, guiding clinical treatment decision-making, and monitoring disease burden and relapse risk.
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Blood testing has identified genes, proteins, and proinflammatory markers associated with depression.
“Similarly, blood testing has identified genes (e.g., NRG1 which is involved in regulation of proliferation, survival, and differentiation of many cell types including neurons and epithelial cells207), proteins (e.g. CD47 which is implicated in neuroinflammatory cascades208), and proinflammatory markers (IL-1β, IL-6)209-211 that are associated with depression.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [208]
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- Authors
- Roman, M., & Irwin, M. R.
- Affiliations
- University of Pennsylvania (US)
- University of California, Los Angeles (US)
- Corresponding author
- Irwin, Michael R.
- ORCID
- Irwin, Michael R.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 83
- Pages
- 7-21
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC6940145
- OpenAlex
- W2973669742
- Cited by
- 132
- References
- 108
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 25 · 2023: 21 · 2022: 25 · 2021: 19 · 2020: 14 · 2019: 1
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- depression, neuroimmunology, inflammation, inflammatory cytokines, IL-1β, interleukin-6, TNF-α, antidepressant response, biomarkers, nonsteroidal anti-inflammatory drugs, celecoxib, aspirin, etanercept, infliximab, ketamine, NMDA receptor antagonism, minocycline, kynurenine pathway, cytokine antagonism
- MeSH terms
- Antidepressive Agents, Depression, Humans, Ketamine, Receptors, N-Methyl-D-Aspartate, Cytokines
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.
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