Inflammation and depression: a causal or coincidental link to the pathophysiology?
Open accessAbstract
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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Prostaglandins increase the release of pro-inflammatory cytokines, suppress Th2 cells, and induce the synthesis of chemokines.
“Prostaglandins increase the release of pro-inflammatory cytokines, suppress Th2 cells, and induce the synthesis of chemokines (158).”
From Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories (2023) · cites this paper as [158]
Dysfunction in serotonergic and dopaminergic transmission contribute to the common mood and cognitive symptoms observed in depression.
“Dysfunction in serotonergic and dopaminergic transmission contribute to the common mood and cognitive symptoms observed in depression142,150.”
From Psychobiological factors of resilience and depression in late life (2019) · cites this paper as [150]
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- Authors
- Leonard, B. E.
- Affiliations
- National University of Ireland (IE)
- Corresponding author
- Leonard, Brian E.
- Venue
- Acta Neuropsychiatrica
- Publisher
- Cambridge University Press (CUP)
- 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
- bronze
- doi.org
- 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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