Cited by 129Tryptophan and brain disordersTreatment of Major DepressionStress Responses and Cortisol

Impact of inflammation on neurotransmitter changes in major depression: An insight into the action of antidepressants

Leonard, Brian E.·2014·Progress in Neuro-Psychopharmacology and Biological Psychiatry

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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Crossref · 10.1016/j.pnpbp.2013.10.018

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94 of 94 references verified0 citation errors · 0 not checkable

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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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