Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Oct;17(4):503-515.
doi: 10.3988/jcn.2021.17.4.503.

How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies

Kyu Man Han  1 , Byung Joo Ham  2
Affiliations
Review

How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies

Kyu Man Han et al. J Clin Neurol. 2021 Oct.

Abstract

This narrative review discusses how peripheral and central inflammation processes affect brain function and structure in depression, and reports on recent peripheral inflammatory marker-based functional and structural magnetic resonance imaging (MRI) studies from the perspective of neural-circuit dysfunction in depression. Chronic stress stimulates the activity of microglial cells, which increases the production of pro-inflammatory cytokines in the brain. In addition, microglial activation promotes a shift from the synthesis of serotonin to the synthesis of neurotoxic metabolites of the kynurenine pathway, which induces glutamate-mediated excitotoxicity in neurons. Furthermore, the region specificity of microglial activation is hypothesized to contribute to the vulnerability of specific brain regions in the depression-related neural circuits to inflammation-mediated brain injury. MRI studies are increasingly investigating how the blood levels of inflammatory markers such as C-reactive protein, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α are associated with functional and structural neuroimaging markers in depression. Functional MRI studies have found that peripheral inflammatory markers are associated with aberrant activation patterns and altered functional connectivity in neural circuits involved in emotion regulation, reward processing, and cognitive control in depression. Structural MRI studies have suggested that peripheral inflammatory markers are related to reduced cortical gray matter and subcortical volumes, cortical thinning, and decreased integrity of white matter tracts within depression-related neural circuits. These neuroimaging findings may improve our understanding of the relationships between neuroinflammatory processes at the molecular level and macroscale in vivo neuralcircuit dysfunction in depression.

Keywords: depression; inflammation; magnetic resonance imaging; major depressive disorder; neuroimaging.

PubMed Disclaimer

Conflict of interest statement

The authors have no potential conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1. Schematic representation of the mechanism of inflammation-induced neural-circuit dysfunction (B) and the related brain regions (A) in depression. Chronic stress leads to the elevation of SNS tone and dysregulation of the HPA axis. This will increase the production of peripheral proinflammatory cytokines, BBB permeability, and infiltration of peripheral monocytes into the brain. The infiltrating monocytes stimulate microglial activity, which promotes a shift from serotonin synthesis to the synthesis of kynurenine-pathway metabolites by stimulating the IDO activity. The increase in neurotoxic kynurenine-pathway metabolites and decrease in KYNA lead to glutamate-mediated excitotoxicity, and the increased proinflammatory cytokines in the CNS exert a direct neurotoxic effect. These processes affect neural-circuit dysfunction in an interactive manner with region-specific neuroinflammatory processes. Dysfunction of the neural circuits involved in emotion regulation, reward processing, cognitive control, and self-referential thinking lead to depression-related psychopathologies. ACC, anterior cingulate cortex; BBB, blood-brain barrier; CNS, central nervous system; dACC, dorsal anterior cingulate cortex; dlPFC, dorsolateral prefrontal cortex; dmPFC, dorsomedial prefrontal cortex; HPA, hypothalamus-pituitary-adrenal; IDO, indoleamine 2,3-dioxygenase; KYNA, kynurenic acid; OFC, orbitofrontal cortex; PCC, posterior cingulate cortex; QUIN, quinolinic acid; rACC, rostral anterior cingulate cortex; SNS, sympathetic nervous system; vlPFC, ventrolateral prefrontal cortex; vmPFC, ventromedial prefrontal cortex; VS, ventral striatum.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bromet E, Andrade LH, Hwang I, Sampson NA, Alonso J, de Girolamo G, et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 2011;9:90. - PMC - PubMed
    1. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386:743–800. - PMC - PubMed
    1. Lerner D, Henke RM. What does research tell us about depression, job performance, and work productivity? J Occup Environ Med. 2008;50:401–410. - PubMed
    1. Gaynes BN, Burns BJ, Tweed DL, Erickson P. Depression and health-related quality of life. J Nerv Ment Dis. 2002;190:799–806. - PubMed
    1. Han KM, Ko YH, Yoon HK, Han C, Ham BJ, Kim YK. Relationship of depression, chronic disease, self-rated health, and gender with health care utilization among community-living elderly. J Affect Disord. 2018;241:402–410. - PubMed