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J Affect Disord. 2014 Dec;169:15-20. doi: 10.1016/j.jad.2014.07.032. Epub 2014 Jul 30.

A review of the relationship between proinflammatory cytokines and major depressive disorder.

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Geriatric Psychiatry Division, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Department of Psychology, Liverpool Hope University, Liverpool, UK.
Geriatric Psychiatry Division, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA; Langone Medical Center, New York University, New York, NY, USA. Electronic address:



Determining etiological factors and reviewing advances in diagnostic modalities sensitive and specific to Major Depressive Disorder (MDD) is of importance in its evaluation and treatment. The inflammatory hypothesis is one of the most prevalent topics concerning MDD and may provide insight into the pathogenesis of depression, development of biomarkers, and ultimately production of more effective depression therapies.


We reviewed several studies to evaluate contemporary concepts concerning proinflammatory cytokines and their relationship to various depressive disorders, the use of anti-inflammatory therapies in MDD treatment, and the application of neuroimaging in conjunction with cytokine profiles from both plasma and CSF as possible diagnostic tools.


Proinflammatory cytokines in both plasma and CSF have been found to influence the progression and severity of depressive disorders in different populations. Studies have shown elevated serum levels of IL-1, IL-6, TNF-α, CRP, and MCP-1 in depressed patients, but have presented mixed results with IL-8 serum levels, and with IL-6 and MCP-1 CSF levels. Anti-inflammatory treatment of MDD may have adjuvant properties with current depression medications. MRI and NIRS neuroimaging confirm neurological abnormalities in the presence of elevated proinflammatory cytokines in depressed or stressed patients.


Heterogeneity of MDD and limited CSF cytokine research complicate the study of MDD pathogenesis.


There is significant evidence that inflammatory processes influence the development and progression of MDD. Future studies with larger arrays of cytokine profiles aided by neuroimaging may provide more sensitive and specific modes of diagnostics in determining MDD etiology and provide guidance in individual therapies.


Immune activation; Inflammatory hypothesis; Major depressive disorder; Neuroimaging; Proinflammatory cytokines

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