Dataset Information

A chicken and egg scenario in psychoneuroimmunology: Bidirectional mechanisms linking cytokines and depression.

ABSTRACT:

Background

Cytokines are an important part of the immune system. Certain cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), have well-described associations with depression. Various mechanisms exist that may explain bidirectional effects of cytokines on depression and vice versa. No recent reviews to our knowledge have comprehensively characterized both these mechanisms and the interaction of these mechanisms using evidence from the molecular level to the clinical level. The goal of this review is to both evaluate the present knowledge base and identify knowledge gaps to help guide future research.

Methods

We conducted an extensive bibliographic search across multiple databases, using both general (e.g. "cytokine") and topic-specific (e.g. "kynurenine") keywords.

Results

We describe the most recent evidence outlining these mechanisms, including the role of the hypothalamic pituitary axis, the kynurenine pathway, and neural circuitry. For relevant topics, we outline the pathways by which cytokine activation may lead to depressive symptoms, and how depressive symptomology may lead to elevations in cytokines. We also identify key areas for future research, including the need for longitudinal clinical studies to examine causality in pertinent mechanisms and modulating factors in the cytokine-depression interaction.

Limitations

Given the numerous potential mechanisms associating cytokines and depressions, this review paper solely focuses on the most commonly described mechanisms at a basic level.

Conclusions

Bidirectional evidence exists for several mechanisms in the relationship between cytokines and depression. However, more work is required to further elucidate the role of these mechanisms in specific clinical populations.

SUBMITTER: Rengasamy M

PROVIDER: S-EPMC9387766 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

A chicken and egg scenario in psychoneuroimmunology: Bidirectional mechanisms linking cytokines and depression.

Rengasamy Manivel M Marsland Anna A Spada Meredith M Hsiung Kimberly K Kovats Tessa T Price Rebecca B RB

Journal of affective disorders reports 20210619

<h4>Background</h4>Cytokines are an important part of the immune system. Certain cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), have well-described associations with depression. Various mechanisms exist that may explain bidirectional effects of cytokines on depression and vice versa. No recent reviews to our knowledge have comprehensively characterized both these mechanisms and the interaction of these mechanisms using evidence from the molecular level to the cli ...[more]

PMID: 35992016

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Project description:Objective: Inflammatory cytokines disturbance is the main result of immune dysregulation, which is widely described in major depressive disorder (MDD). However, the potential causal relationship between these two factors has not been discovered. Therefore, the purpose of this study was to investigate the causal relationship between inflammatory cytokines and MDD risk by using the two-sample Mendelian randomization (MR) analysis. Method: Two genetic instruments obtained from publicly available gene profile data were utilized for the analysis. We obtained the genetic variation data of 41 inflammatory cytokines from genome-wide association studies (GWAS) meta-analysis of 8293 individuals of Finnish descent. The MDD data, including 135,458 MDD cases and 344,901 controls, were obtained from the Psychiatric Genomics Consortium Database. For the Mendelian randomization (MR) estimation, several methods were employed, namely, MR-Egger regression, inverse-variance weighted (IVW), weighted median, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods. Result: A causal relationship was identified between the genetically proxied levels of Interleukin (IL) -18, IL-1β, and Regulated upon activation normal T cell expressed and secreted (RANTES) and the risk of MDD (OR = 0.968, 95%CI = 0.938, 0.998, p = 0.036; OR = 0.875, 95%CI = 0.787, 0.971, p = 0.012; OR = 0.947, 95%CI = 0.902, 0.995, p = 0.03; respectively). However, our Mendelian randomization (MR) estimates provided no causality of MDD on inflammatory cytokines. Conclusion: Our study elucidates the connection between inflammatory cytokines and MDD by using MR analysis, thereby enhancing our comprehension of the potential mechanisms. By identifying these associations, our findings hold substantial implications for the development of more effective treatments aimed at improving patient outcomes. However, further investigation is required to fully comprehend the exact biological mechanisms involved.

Dataset Information

A chicken and egg scenario in psychoneuroimmunology: Bidirectional mechanisms linking cytokines and depression.

Background

Methods

Results

Limitations

Conclusions

Publications

A chicken and egg scenario in psychoneuroimmunology: Bidirectional mechanisms linking cytokines and depression.

Similar Datasets

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