The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression
Abstract
Cytokines are pleiotropic molecules with important roles in inflammatory responses. Pro-inflammatory cytokines and neuroinflammation are important not only in inflammatory responses but also in neurogenesis and neuroprotection. Sustained stress and the subsequent release of pro-inflammatory cytokines lead to chronic neuroinflammation, which contributes to depression. Hippocampal glucocorticoid receptors (GRs) and the associated hypothalamus-pituitary-adrenal (HPA) axis have close interactions with pro-inflammatory cytokines and neuroinflammation. Elevated pro-inflammatory cytokine levels and GR functional resistance are among the most widely investigated factors in the pathophysiology of depression. These two major components create a vicious cycle. In brief, chronic neuroinflammation inhibits GR function, which in turn exacerbates pro-inflammatory cytokine activity and aggravates chronic neuroinflammation. On the other hand, neuroinflammation causes an imbalance between oxidative stress and the anti-oxidant system, which is also associated with depression. Although current evidence strongly suggests that cytokines and GRs have important roles in depression, they are essential components of a whole system of inflammatory and endocrine interactions, rather than playing independent parts. Despite the evidence that a dysfunctional immune and endocrine system contributes to the pathophysiology of depression, much research remains to be undertaken to clarify the cause and effect relationship between depression and neuroinflammation.
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Alterations in peripheral inflammatory profile are observed in several neurodevelopmental disorders including ADHD.
“Alterations in the peripheral inflammatory profile are observed in several neurodevelopmental disorders (Kim et al., 2016; Landaas et al., 2010; Monji et al., 2013; Vargas et al., 2005), including ADHD”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Kim et al., 2016
A number of neuropsychiatric disorders including ASD, schizophrenia, depression, anxiety, and bipolar disorder have been associated with exposure to increased peripheral and/or central inflammatory response during perinatal development.
“a number of neuropsychiatric disorders including ASD (Vargas et al., 2005), schizophrenia (Monji et al., 2013), depression (Kim et al., 2016), anxiety, and bipolar disorder (Landaas et al., 2010) have also been associated with exposure to an increased peripheral and/or central inflammatory response during perinatal development.”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Kim et al., 2016
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- Authors
- Kim, Y.-K., Na, K.-S., Myint, A.-M., & Leonard, B. E.
- Affiliations
- Korea University (KR)
- Gachon University Gil Medical Center (KR)
- Ludwig-Maximilians-Universität München (DE)
- Ollscoil na Gaillimhe – University of Galway (IE)
- Corresponding author
- Na, Kyoung-Sae
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 64
- Pages
- 277-284
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2147242210
- Semantic Scholar
- 545b5d233c6b106452bdc7f3042afc1e90de1b42
- Cited by
- 620
- References
- 36
- Citations by year
- 2026: 28 · 2025: 55 · 2024: 71 · 2023: 75 · 2022: 79 · 2021: 86 · 2020: 63 · 2019: 50 · 2018: 50 · 2017: 42 · 2016: 18 · 2015: 3
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- inflammatory cytokines, neuroinflammation, major depressive disorder, neurogenesis, neuroendocrine system, glucocorticoid receptor, hypothalamic-pituitary-adrenal axis, chronic stress, glucocorticoid resistance, oxidative stress, endocrine-immune interaction, depression pathophysiology
- MeSH terms
- Animals, Depressive Disorder, Major, Major Depressive Disorder, Humans, Neurosecretory Systems, Neuroimmunomodulation, Cytokines, Oxidative Stress, Neurogenesis
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