Role of neuro-immunological factors in the pathophysiology of mood disorders
Abstract
Mood disorders, despite the widespread availability of monoamine-based antidepressant treatments, are associated with persistently high rates of disability, together with elevated rates of mortality due to suicide, cardiovascular disease, and other causes. The development of more effective treatments has been hindered by the lack of knowledge about the etiology and pathogenesis of mood disorders. An emerging area of science that promises novel pathways to antidepressant and mood stabilizing therapies surrounds evidence that immune cells and their signaling play a major role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). Here, we review evidence that the release of neuroactive cytokines, particularly interleukins such as IL-1β, IL-6, and TNF-α, is altered in these disorders and discuss mechanisms such as the ATP-gated ion channel P2X7, through which cytokine signaling can influence neuro-glial interactions. Brain P2X7, an emerging target and antagonism of P2X7 holds promise as a novel mechanism for targeting treatment-resistant depression. We further discuss the role of microglia and astroglia in central neuroinflammation and their interaction with the peripheral immune system We present extant clinical evidence that bolsters the role of neuroinflammation and neuroactive cytokines in mood disorders. To that end, the role of clinical imaging by probing neuroinflammatory markers is also discussed briefly. Finally, we present data using preclinical neuroinflammation models that produce depression-like behaviors in experimental animals to identify neuroinflammatory mechanisms which may aid in novel neuroimmune target identification for the development of exciting pharmacological interventions in mood disorders.
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Immune dysregulation is implicated in the pathophysiology of both bipolar and major depressive disorder.
“Solid research of the past two decades suggests a distinct crosstalk between the central nervous and the peripheral immune system, and has offered mounting evidence of immune dysregulation in affective disorders through several molecular pathways [24].”
From Immune Cell Ratios Are Higher in Bipolar Affective than Unipolar Depressive Disorder and Modulated by Mood Episode: A Retrospective, Cross-Sectional Study (2023) · cites this paper as [24]
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“Solid research of the past two decades suggests a distinct crosstalk between the central nervous and the peripheral immune system, and has offered mounting evidence of immune dysregulation in affective disorders through several molecular pathways [24].”
Background
- Authors
- Bhattacharya, A., Derecki, N. C., Lovenberg, T. W., & Drevets, W. C.
- Corresponding author
- Bhattacharya, Anindya
- Venue
- Psychopharmacology
- Published
- 2016-01-23
- Volume
- 233
- Issue
- 9
- Pages
- 1623-1636
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2285307127
- Cited by
- 149
- References
- 37
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 8 · 2023: 15 · 2022: 10 · 2021: 16 · 2020: 15 · 2019: 20 · 2018: 22 · 2017: 18 · 2016: 10
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- mood disorders, neuroinflammation, neuroimmune signaling, cytokines, IL-1β, interleukin-6, TNF-α, P2X7 receptor, microglia, astrocytes, treatment-resistant depression, major depressive disorder, bipolar disorder
- MeSH terms
- Animals, Central Nervous System, Humans, Inflammation, Psychoneuroimmunology, Cytokines, Mood Disorders
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