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Role of Neuro-Immunological Factors in the Pathophysiology of Mood Disorders: Implications for Novel Therapeutics for Treatment Resistant Depression

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Inflammation-Associated Depression: Evidence, Mechanisms and Implications

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 31))

Abstract

Mood disorders are associated with persistently high rates of morbidity and mortality, despite the widespread availability of antidepressant treatments. One limitation to extant therapeutic options has been that nearly all approved antidepressant pharmacotherapies exert a similar primary action of blocking monoamine transporters, and few options exist for transitioning treatment resistant patients to alternatives with distinct mechanisms. An emerging area of science that promises novel pathways to antidepressant and mood-stabilizing therapies has followed from evidence that immunological factors play major roles in the pathophysiology of at least some mood disorder subtypes. Here we review evidence that the compounds that reduce the release or signaling of neuroactive cytokines, particularly IL-1β, IL-6, and TNF-α, can exert antidepressant effects in subgroups of depressed patients who are identified by blood-based biomarkers associated with inflammation. Within this context we discuss the role of microglia in central neuroinflammation, and the interaction between the peripheral immune system and the central synaptic microenvironment during and after neuroinflammation. Finally we review data using preclinical neuroinflammation models that produce depression-like behaviors in experimental animals to guide the discovery of novel neuro-immune drug targets.

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Financial Disclosures

The authors report potential conflicts of interest: A.B. and W.C.D. are employees of Janssen Research & Development, LLC, of Johnson & Johnson, and are stock-holders in Johnson & Johnson, Inc.

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Authors and Affiliations

  1. Neuroscience Drug Discovery, Janssen Research & Development, LLC, Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA, 92121, USA

    Anindya Bhattacharya

  2. Neuroscience, Janssen Research & Development, LLC, Titusville, NJ, 08560, USA

    Wayne C. Drevets

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  1. Anindya Bhattacharya
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  2. Wayne C. Drevets
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Correspondence to Anindya Bhattacharya .

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Editors and Affiliations

  1. Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Robert Dantzer

  2. Nutrition and Integrative Neurobiology, INRA, University of Bordeaux, Bordeaux, France

    Lucile Capuron

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Bhattacharya, A., Drevets, W.C. (2016). Role of Neuro-Immunological Factors in the Pathophysiology of Mood Disorders: Implications for Novel Therapeutics for Treatment Resistant Depression. In: Dantzer, R., Capuron, L. (eds) Inflammation-Associated Depression: Evidence, Mechanisms and Implications. Current Topics in Behavioral Neurosciences, vol 31. Springer, Cham. https://doi.org/10.1007/7854_2016_43

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