Cited by 409Tryptophan and brain disordersStress Responses and CortisolTreatment of Major Depression

Inflammation and depression: a causal or coincidental link to the pathophysiology?

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Leonard, Brian E.·2018·Acta Neuropsychiatrica

Abstract

This review summarises the evidence that chronic low grade inflammation triggers changes that contribute to the mental and physical ill health of patients with major depression. Inflammation, and the activation of the hypothalamic pituitary axis by stress, are normal components of the stress response but when stress is prolonged and the endocrine and immune system become chronic resulting in the activation of the peripheral macrophages, the central microglia and hypercortisolemia, the neuronal networks are damaged and become dysfunctional. The proinflammatory cytokines, in addition to activating the hypothalamic–pituitary–adrenal axis and thereby increasing cortisol synthesis, also activate the tryptophan–kynurenine pathway. This results in the synthesis of the neurotoxic N-methyl-d-aspartate (NMDA) glutamate agonist quinolinic acid and 3-hydroxykynurenine thereby enhancing oxidative stress and contributes to neurodegeneration which characterise major depression particularly in late life.While antidepressants attenuate some of the endocrine and immune changes caused by inflammation, not all therapeutically effective antidepressants do so. This suggests that drugs which specifically target the immune, endocrine and neurotransmitter systems may be more effective antidepressants.The preliminary clinical evidence that some non-steroidal anti-inflammatory drugs, such as the cyclooxygenase 2 inhibitor celecoxib, can enhance the response to standard antidepressant treatment is therefore considered and a critical assessment made of the possible limitations of such an approach to novel antidepressant development.

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  1. [51]51. YARON I, SHIRAZI I, JUDOVICH R, LEVARTOVSKY D, CASPI D, YARON M. Fluoxetine and amitriptyline inhibit nitric oxide, prostaglandin E2, and hyaluronic acid production in human synovial cells and synovial tissue cultures. Arthritis Rheum 1999;42:2561-2568.
  2. [82]82. MAES M, MELTZER HY. The serotonin hypothesis of major depression. In: Bloom FE, editor. Psychopharmacology the 3rd generation of progress. NY: Raven Press, 1995; p. 946-993.
  3. [97]97. WEGENER G, MATHÉ AA. Nitric oxide signaling in depression and antidepressant action. In: Lopez-Munoz F, Alamo C, editors. Neurobiology of depression. Frontiers in neuroscience. Boca Raton: CRC Press, 2012; p. 341-370.

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Authors
Leonard, B. E.
Affiliations
National University of Ireland (IE)
Corresponding author
Leonard, Brian E.
Venue
Acta Neuropsychiatrica
Published
2017-06-23
Volume
30
Issue
1
Pages
1-16
ISSN
  • 0924-2708 (ISSN-L)
  • 1601-5215
OpenAlex
W2580103234
Cited by
409
References
131
Citations by year
2026: 22 · 2025: 50 · 2024: 34 · 2023: 67 · 2022: 55 · 2021: 59 · 2020: 54 · 2019: 35 · 2018: 26 · 2017: 7
FWCI
2.25
Type
journal article
Language
en
Open access
Locations
  • Acta Neuropsychiatrica (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
low-grade inflammation, major depressive disorder, hypothalamic-pituitary-adrenal axis, inflammatory cytokines, kynurenine pathway, quinolinic acid, 3-hydroxykynurenine, oxidative stress, neurodegeneration, macrophages, microglia, hypercortisolism, antidepressants, celecoxib, COX-2 inhibitors, geriatric depression
MeSH terms
Animals, Brain, Major Depressive Disorder, Humans, Inflammation, Prostaglandins, Illness Behavior

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