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

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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

DOI 10.1016/j.pnpbp.2013.10.018

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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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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)
DOI: 10.1016/j.pnpbp.2013.10.018
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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 (medical) › 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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Impact of inflammation on neurotransmitter changes in major depression: An insight into the action of antidepressants

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