The role of neuroinflammation and neurovascular dysfunction in major depressive disorder

Sang Won Jeon, Yong Ku Kim

    Research output: Contribution to journalReview articlepeer-review

    85 Citations (Scopus)


    Although depression has generally been explained with monoamine theory, it is far more multifactorial, and therapies that address the disease’s pathway have not been developed. In this context, an understanding of neuroinflammation and neurovascular dysfunction would enable a more comprehensive approach to depression. Inflammation is in a sense a type of allostatic load involving the immune, endocrine, and nervous systems. Neuroinflammation is involved in the pathophysiology of depression by increasing proinflammatory cytokines, activating the hypothalamus–pituitary–adrenal axis, increasing glucocorticoid resistance, and affecting serotonin synthesis and metabolism, neuronal apoptosis and neurogenesis, and neuroplasticity. In future, identifying the subtypes of depression with increased vulnerability to inflammation and testing the effects of inflammatory modulating agents in these patient groups through clinical trials will lead to more concrete conclusions on the matter. The vascular depression hypothesis is supported by evidence for the association between vascular disease and late-onset depression and between ischemic brain lesions and distinctive depressive symptoms. Vascular depression may be the entity most suitable for studies of the mechanisms of depression. Pharmacotherapies used in the prevention and treatment of cerebrovascular disease may help prevent vascular depression. In future, developments in structural and functional imaging, electrophysiology, chronobiology, and genetics will reveal the association between depression and brain lesions. This article aims to give a general review of the existing issues examined in the literature pertaining to depression-related neuroinflammatory and vascular functions, related pathophysiology, applicability to depression treatment, and directions for future research.

    Original languageEnglish
    Pages (from-to)179-192
    Number of pages14
    JournalJournal of Inflammation Research
    Publication statusPublished - 2018 May 8

    Bibliographical note

    Funding Information:
    This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, South Korea (HC15C1405).

    Publisher Copyright:
    © 2018 Jeon and Kim.


    • Depressive disorder
    • Neuroinflammation
    • Psychoneuroimmunology
    • Vascular depression
    • Vascular disease

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology


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