The Role of Inflammation in Depression and Fatigue

Abstract

Depression and fatigue are conditions responsible for heavy global societal burden, especially in patients already suffering from chronic diseases. These symptoms have been identified by those affected as some of the most disabling symptoms which affect the quality of life and productivity of the individual. While many factors play a role in the development of depression and fatigue, both have been associated with increased inflammatory activation of the immune system affecting both the periphery and the central nervous system (CNS). This is further supported by the well-described association between diseases that involve immune activation and these symptoms in autoimmune disorders, such as multiple sclerosis and immune system activation in response to infections, like sepsis. Treatments for depression also support this immunopsychiatric link. Antidepressants have been shown to decrease inflammation, while higher levels of baseline inflammation predict lower treatment efficacy for most treatments. Those patients with higher initial immune activation may on the other hand be more responsive to treatments targeting immune pathways, which have been found to be effective in treating depression and fatigue in some cases. These results show strong support for the hypothesis that depression and fatigue are associated with an increased activation of the immune system which may serve as a valid target for treatment. Further studies should focus on the pathways involved in these symptoms and the development of treatments that target those pathways will help us to better understand these conditions and devise more targeted treatments.

Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms

“…Cytokines are soluble intercellular signaling molecules that are involved in the pathophysiology of several mental disorders through affecting neurotransmitter synthesis, release, and reuptake [79], as well as regulating BDNF expression [80]. In regard to mental disorders, there is a growing body of research investigating the possible cross-talk between pathological alterations in sleep patterns [81], depression [82], and anxiety disorders [83] and inflammation-related diseases that involve increased inflammatory cytokines release. On the other hand, different studies have also shown that a deficit of anti-inflammatory cytokines, such as transforming growth factor-β1 (TGF-β1), can contribute to the pathogenesis of depressive disorders [84].…”

Variation in chemokines plasma concentrations in primary care depressed patients associated with Internet-based cognitive-behavioral therapy

“…For instance, cytokines have been suggested as predictors of the antidepressant effect of exercise 13 , and meta-analysis has shown that certain types of antidepressants reduce pro-inflammatory factors such as C-reactive protein, tumor necrosis factor-α and interleukin −1β, showing some interaction between antidepressant medication, depression and inflammation 14 . Another review showed that the effects of antidepressant drugs have been consistently linked to decreased inflammation 15 . However, despite the extensive research into cytokines in this area, a related family of immune system-derived signaling proteins, the chemokines, has been relatively neglected 7 .…”

Functional Neuroimaging in Psychiatry—Aiding in Diagnosis and Guiding Treatment. What the American Psychiatric Association Does Not Know

“…For example, treating multiple sclerosis with powerful antiinflammatories was associated with reduction of depressive symptoms (68). Conversely, treatment of hepatitis C with interferon alpha, a powerful activator of an inflammatory response, induces depression in roughly 20% of patients (72,73). Work over the last decade has characterized the nature of the inflammatory processes underlying depression and its possible influence on the brain.…”

“…Briefly, cytokines are elevated in a portion of patients suffering from depression. In particular, tumor necrosis factor alpha (TNFa), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-13 (IL-13), interleukin-18 (IL-18), Creactive protein (CRP), chemokine-2 (CCL2), and chemokine-11 (CCL11) are elevated in depression based on multiple metaanalyses (68,71,73). But how inflammatory cytokines induce depressive symptoms remain incompletely understood.…”

“…The IL-6 antagonist, tocilizumab, also shows anti-depressant qualities (76). Similarly, rituximab, an antibody which inhibits B cell activity, can induce decreased fatigue and improved mood in patients treated for rheumatoid arthritis (73). Recently, the antibiotic, minocycline, which has immunomodulatory effects, has been shown to improve depressive symptoms (77).…”