Inflammation: a mechanism of depression?

Abstract

In recent decades, major depression has become more prevalent and research has shown that immune activation and cytokine production may be involved. This review is mainly focused on the contribution of infl ammation to depression. We fi rst briefl y introduce the infl ammatory biomarkers of depression, then discuss the sources of cytokines in the brain, and fi nally describe the neuroimmunological mechanisms underlying the association between infl ammation and depression.Keywords: depression; infl ammation; cytokines; hypothalamic-pituitary-adrenal axis; 5-HT; neuroplasticity ·Review· IntroductionThe prevalence of major depression has increased dramatically over the past few decades [1] , and women are nearly twice as likely as men to develop depressive disorder [2] . Depression is classified as a brain disorder, but its symptomatology includes some behaviors that also occur during chronic infl ammatory stress [3] . Research has shown that immune activation and the production of cytokines may be involved in depression [4] , so this relationship has received much attention. In fact, three causal pathways have been proposed: depression to inflammation, inflammation to depression, and a bidirectional relationship [5] . In this review, we focus on the impact of inflammation on depression and the underlying mechanisms. Cytokines are small cell-signaling proteins that mediate and regulate immune responses and inflammation, and can be divided into two categories:the pro-inflammatory cytokines interleukin (IL)-1 β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, and the anti-inflammatory cytokines IL-1Rα, IL-4, IL-10, and transforming growth factor (TGF)-β1. Generally, t he proinfl ammatory cytokines promote systemic infl ammation and are essential for the initiation of an infl ammatory response to disease [6] , while the anti-inflammatory cytokines antagonize these actions to reduce inflammation and promote healing [6,7] . Moreover, some cytokines play dual roles [8] . In the central nervous system (CNS), the cellular source, function, and mechanisms of action of cytokines differ from those in the periphery. In the following, we briefl y introduce the current research on infl ammatory biomarkers of depression. Infl ammatory Biomarkers of DepressionSo far, there are neither universally accepted or defi nitive biomarkers of depression [9] , nor effective methods to assess the severity, endophenotypes, or response to treatment [10] .However, sufficient evidence has suggested changes in the circulating levels of cytokines in depressed patients, which can be reversed by antidepressant treatments [11,12] .So, many studies have aimed to clarify the neurobiological changes in depression and to establish inflammatory biomarkers. The peripheral levels of IL-6, TNF-α, and IL-1β are increased in patients with depression [13][14][15][16][17] , and antidepressant treatments reverse this effect [18][19][20] . These consistent results demonstrate that IL-6, TNF-α, and IL-1β are putative biomarkers for depression. However, due to the he...

New hypothesis and treatment targets of depression: an integrated view of key findings

“…When the immune system responds to stressors such as disease, injury, infection, or psychosocial factors, cytokines are secreted to regulate body functions [40] . Much evidence indicates that changes in infl ammatory cytokines are closely associated with the occurrence of depression, leading to the cytokine hypothesis of depression which proposes that depression is often associated with immune disorders, activation of the infl ammatory response system, and elevated infl ammatory cytokines under stress conditions.…”

Antidepressant Augmentation With Anti-Inflammatory Agents

“…[1][2][3][4] If this is true, then anti-inflammatory drugs may improve depression outcomes by attenuating the neuroinflammatory changes 5 or by other mechanisms, such as increased norepinephrine and serotonin levels. 6 Data from animal models show that NSAIDs in monotherapy 7,8 and in combination with conventional antidepressants 5 indeed attenuate indices of inflammation and depression.…”

Chronic and treatment-resistant depression

“…A bidirectional relationship between inflammation and depression is thought to exist (Han & Yu, 2014). Particular attention has been given to cytokines, cell signalling proteins that mediate and regulate immune response and depression (Han & Yu, 2014).…”

“…A bidirectional relationship between inflammation and depression is thought to exist (Han & Yu, 2014). Particular attention has been given to cytokines, cell signalling proteins that mediate and regulate immune response and depression (Han & Yu, 2014). Pro-inflammatory cytokines promote the inflammatory response whilst anti-inflammatory cytokines work to reduce inflammation and initiate healing (Han & Yu, 2014).…”

“…Particular attention has been given to cytokines, cell signalling proteins that mediate and regulate immune response and depression (Han & Yu, 2014). Pro-inflammatory cytokines promote the inflammatory response whilst anti-inflammatory cytokines work to reduce inflammation and initiate healing (Han & Yu, 2014). Efforts to identify neuroendocrine and immune dysfunction in depression have focused on alterations in hypothalamic-pituitary adrenal (HPA) regulation and other neuroendocrine changes such as elevated cortisol levels as well as altered immune function (Pariante & Lightman, 2008;Hasler, 2010).…”