The Role of Inflammation in Depression and Fatigue

Chieh-Hsin Lee, Fabrizio Giuliani, Chieh-Hsin Lee, Fabrizio Giuliani

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.

Keywords: autoimmune diseases; depression; fatigue; inflammation; psychoneuroimmunology.

Figures

Figure 1
Figure 1
Links between peripheral inflammation and changes in the CNS in depression and fatigue. Increased inflammation is seen in the periphery in both depression and fatigue. This inflammation leads to increased permeability of the BBB, allowing for easier entry of inflammatory molecules or immune cells into the CNS. Inflammatory signaling in the CNS leads to both structural and functional changes, with the hippocampus being the location of many of the changes. BBB, Blood–brain barrier; CNS, Central nervous system; CRP, C-reactive protein; IFN, Interferon; IFNAR1, Interferon-alpha/beta receptor alpha chain; IL, Interleukin; IP-10, Interferon gamma-induced protein 10; TNF, Tumor necrosis factor; NK, Natural killer cell; Treg, Regulatory T cell; LTP, Long-term potentiation.

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