Different levels of pro- and anti-inflammatory cytokines in patients with unipolar and bipolar depression

Mao, Ruizhi; Zhang, Chen; Chen, Jun; Zhao, Guangsheng; Zhou, Rubai; Wang, Fan; Xu, Jingjing; Yang, Tao; Su, Yousong; Huang, Jia; Wu, Zhiguo; Cao, Lan; Wang, Yong; Hu, Ye; Yuan, Chen; Yi, Zhenghui; Wu, Hong; Wang, Zuowei; Peng, Daihui; Fang, Yiru

doi:10.1016/j.jad.2018.04.115

Cited by 62 publications

(40 citation statements)

References 47 publications

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“…Thus, altered levels of peripheral cytokines can probably be considered a stable biomarker of the disorder. BD patients show lower levels of plasma TNF-a and IL-13 (111), and serum IL-1b (112) compared to MDD patients. On the other hand, BD patients presented higher Creactive protein, sTNFR1, soluble IL-6 receptor (sIL-6R), and MCP-1 levels compared to MDD patients (33,113).…”

Section: Immune Markers As Clinical Outcome and Diagnostic Predictorsmentioning

confidence: 99%

Neuroinflammation in Bipolar Depression

et al. 2020

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Bipolar disorder (BD) is a leading cause of worldwide disability among mood disorders. Pathological mechanisms are still vastly unclear, and current treatments with conventional medications are often unsatisfactory in maintaining symptoms control and an adequate quality of life. Consequently, current research is focusing on shedding new light on disease pathogenesis, to improve therapeutic effectiveness. Recent evidence has suggested a prominent role of inflammation in mood disorders. Elevated levels of peripheral proinflammatory mediators have been reported in BD, as well as in other mood disorders, and people with systemic autoimmune diseases have an increased risk of developing BD. These immunological alterations are stable, and current medications are unable to alter peripheral concentrations even when clinical improvement is evident. These findings have also been replicated in the central nervous system (CNS) milieu, whereas genetic studies have shown that these immune alterations are not due to the disorder itself, being detectable before the illness onset. Moreover, these inflammatory modifications seem to be affected by and linked to other biomarkers of the disorder, such as alterations of white matter (WM) microstructure, metabolism, kynurenine pathway, and circadian rhythmicity. Finally, these immune variations seem to be useful as predictors of therapeutic responsiveness to medications, and in discriminating between clinically different outcomes. The objective of this review is to summarize available evidence on the connection between inflammation and BD, focusing on peripheral inflammatory markers and recent findings on their connection with other typical features of BD, to outline a general overview of the disorder. Moreover, it is meant to analyze the issues with data gathering and interpretation, given the partially contradictory and inconsistent nature of results.

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Section: Immune Markers As Clinical Outcome and Diagnostic Predictorsmentioning

confidence: 99%

Neuroinflammation in Bipolar Depression

et al. 2020

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“…Even though these categories are often referred to in the psychoimmunological literature, these are neither distinct nor generally accepted categories for the classification of cytokines. However, this functional classification might help to understand recent research papers on pro-inflammatory, anti-inflammatory, T H 1 and T H 2 cytokines in depression [e.g., (74–77)]. One must also take into account that cytokines can have different effects on different cells and thus may have pro- but also anti-inflammatory properties.…”

Section: Cytokines Within the Immune Systemmentioning

confidence: 99%

Cytokine Research in Depression: Principles, Challenges, and Open Questions

et al. 2019

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Cytokines have been implicated in the pathology of depression. Currently, the evidence is based on cross-sectional studies and meta-analytic research comparing blood concentrations of T helper type 1 (TH1), T helper type 2 (TH2), pro-inflammatory or anti-inflammatory cytokines of patients with a depressive disorder to those of healthy controls. Additionally, multiple longitudinal studies have investigated cytokine levels during antidepressant treatment. According to the current literature, it seems that peripheral levels of interleukin (IL)-6, IL-10, IL-12, IL-13, and tumor necrosis factor (TNF)-α are elevated and that interferon (IFN)-γ levels are lower in patients with depression compared to healthy controls. However, the overlap of cytokine values between acutely depressed patients, remitted and recovered patients and healthy controls is considerable. Thus, the discriminative power of cytokine concentrations between depressed and non-depressed people is likely weak. Treatment with certain antidepressants appears to decrease peripheral levels of IL-6, IL-10, and TNF-α. However, weight gain-inducing psychopharmacological substances, such as the antidepressant mirtazapine, have been reported to potentially increase the production of pro-inflammatory cytokines. Even though cytokines are often discussed as biomarkers for depression, they have also been shown to be altered in other psychiatric disorders. Moreover, many environmental, social, psychological, biological, and medical factors are also associated with cytokine changes. Thus, cytokine alterations seem extremely unspecific. The interpretation of the results of these studies remains a challenge because it is unknown which type of cells are most responsible for cytokine changes measured in the blood nor have the main target cells or target tissues been identified. The same cytokine can be produced by multiple cell types, and the same cell can produce various cytokines. Additionally, redundancy, synergy, antagonism, and signaling cascades of cytokine signaling must be considered. Cytokines might not be associated with the diagnosis of depression according to the currently used diagnostic manuals, but rather with specific subtypes of depression, or with depressive symptoms across different psychiatric diagnoses. Therefore, the currently available diagnostic systems may not be the ideal starting point for psychiatric cytokine research.

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“…The sickness-related psychopathological symptoms during infection and inflammation are mediated by increasing multiple proinflammatory cytokines, namely IL-1ß, IL-6, TNF-α and IFN-γ. Intriguingly, an imbalance among them was detected in the serum of patients with MDD (Young et al, 2014 ; Mao et al, 2018 ). Some antidepressants have shown strong anti-inflammatory response, for example, selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRI and SNRI, respectively) are the first choice pharmacological options for treating MDD.…”

Section: Microglia Neuroinflammation and Mddmentioning

confidence: 99%

Switching of the Microglial Activation Phenotype Is a Possible Treatment for Depression Disorder

Zhang

You

2018

Front. Cell. Neurosci.

230

158

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Major depressive disorder (MDD) is a common emotional cognitive disorder that seriously affects people’s physical and mental health and their quality of life. Due to its clinical and etiological heterogeneity, the molecular mechanisms underpinning MDD are complex and they are not fully understood. In addition, the effects of traditional drug therapy are not ideal. However, postmortem and animal studies have shown that overactivated microglia can inhibit neurogenesis in the hippocampus and induce depressive-like behaviors. Nonetheless, the molecular mechanisms by which microglia regulate nerve regeneration and determine depressive-like behaviors remain unclear. As the immune cells of the central nervous system (CNS), microglia could influence neurogenesis through the M1 and M2 subtypes, and these may promote depressive-like behaviors. Microglia may be divided into four main states or phenotypes. Under stress, microglial cells are induced into the M1 type, releasing inflammatory factors and causing neuroinflammatory responses. After the inflammation fades away, microglia shift into the alternative activated M2 phenotypes that play a role in neuroprotection. These activated M2 subtypes consist of M2a, M2b and M2c and their functions are different in the CNS. In this article, we mainly introduce the relationship between microglia and MDD. Importantly, this article elucidates a plausible mechanism by which microglia regulate inflammation and neurogenesis in ameliorating MDD. This could provide a reliable basis for the treatment of MDD in the future.

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Different levels of pro- and anti-inflammatory cytokines in patients with unipolar and bipolar depression

Cited by 62 publications

References 47 publications

Neuroinflammation in Bipolar Depression

Neuroinflammation in Bipolar Depression

Cytokine Research in Depression: Principles, Challenges, and Open Questions

Switching of the Microglial Activation Phenotype Is a Possible Treatment for Depression Disorder

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