Impact of inflammation on neurotransmitter changes in major depression: An insight into the action of antidepressants
Abstract
This review summarises the evidence that chronic low grade inflammation plays an important role in the pathology of depression. Evidence is provided that pro-inflammatory cytokines, together with dysfunctional endocrine and neurotransmitter systems, provide a network of changes that underlie depression and may ultimately contribute to the neurodegenerative changes that characterise depression in the elderly. Antidepressants attenuate the inflammatory changes and hypercortisolaemia by reducing the release of the pro-inflammatory cytokines from activated microglia, and by sensitizing the glucocorticoids receptors in the HPA axis. These effects correlate with an improvement in monoamine neurotransmitter function. The possible mechanisms whereby this cascade of changes occurs are outlined. In conclusion, the mechanisms whereby antidepressants act should now consider the involvement of the immune and endocrine systems in addition to the central neurotransmitters. This may open up possibilities for a new generation of antidepressants in the future.
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Emerging evidence suggests that immune mechanisms may contribute to the therapeutic benefits of some antidepressants.
“However, emerging evidence suggests that immune mechanisms may contribute to the therapeutic benefits of some of these drugs [8].”
Our findings are consistent with the view that antidepressants may diminish peripheral inflammation and its impact on the brain.
“Thus, our findings are consistent with the view that antidepressants may diminish peripheral inflammation and its impact on the brain [8] although our analysis indicate that these effects may not be consistently associated with treatment response.”
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- Authors
- Leonard, B. E.
- Affiliations
- Ollscoil na Gaillimhe – University of Galway (IE)
- Corresponding author
- Leonard, Brian E.
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 48
- Pages
- 261-267
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W1966170485
- Cited by
- 129
- References
- 94
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 9 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 11 · 2018: 6 · 2017: 15 · 2016: 11 · 2015: 19 · 2014: 14
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- 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
- major depressive disorder, low-grade inflammation, inflammatory cytokines, antidepressant mechanism, microglia, glucocorticoid receptor, hypothalamic-pituitary-adrenal axis, hypercortisolism, monoamines, neuroinflammation, endocrine dysfunction
- MeSH terms
- Antidepressive Agents, Major Depressive Disorder, Humans, Inflammation, Receptors, Neurotransmitter
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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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