Neuroinflammation

Neuroinflammation is simply the natural brain response to injury, infection, or disease.² Inflammation is initiated and controlled by white blood cells in the body, but in the central nervous system (CNS) neuroinflammation is mediated principally by microglia.² The microglial cells patrol the CNS, monitoring for signs of injury or infection.² Activation of glial cells quickly leads to the release of both pro- and anti-inflammatory cytokines.² The final effect of glial activation is dependent on the balance between opposing responses; it has been suggested that glial activation initially serves a protective function, but that continuous activation can lead to exaggerated release of proinflammatory cytokines, and neuronal damage.² The hippocampus is a region of the brain with a notably high density of microglia; patients with MDD typically have smaller hippocampal volumes than healthy controls^1,8

References:

1. Brites D, Fernandes A. Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation. Front Cell Neurosci 2015; 9: 476.
2. Hurley LL, Tizabi Y. Neuroinflammation, neurodegeneration and depression. Neurotox Res 2013; 23 (2): 131–144.
3. Marx W, Penninx BWJH, Solmi M, et al. Major depressive disorder. Nat Rev Dis Primers 2023; 9 (1): 44.
4. Pitharouli MC, Hagenaars SP, Glanville KP, et al. Elevated C-reactive protein in patients with depression, independent of genetic, health, and psychosocial factors: results from the UK Biobank. Am J Psychiatry 2021; 178 (6): 522–529.
5. Mac Giollabhui N, Ng TH, Ellman LM, Alloy LB. The longitudinal associations of inflammatory biomarkers and depression revisited: systematic review, meta-analysis, and meta-regression. Mol Psychiatry 2021; 26 (7): 3302–3314.
6. Enache D, Pariante CM, Mondelli V. Markers of central inflammation in major depressive disorder: A systematic review and meta-analysis of studies examining cerebrospinal fluid, positron emission tomography and post-mortem brain tissue. Brain Behav Immun 2019; 81: 24–40.
7. Pastis I, Santos MG, Paruchuri A. Exploring the role of inflammation in major depressive disorder: beyond the monoamine hypothesis. Front Behav Neurosci 2024; 17: 1282242.
8. Kempton MJ, Salvador Z, Munafò MR, et al. Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder. Arch Gen Psychiatry 2011; 68 (7): 675–690.