Peripheral cytokine levels across psychiatric disorders: A systematic review and network meta-analysis

Zhang, Yuan; Wang, Jingjing; Ye, Yu; Zou, Yazhu; Chen, Wei; Wang, Zuxing; Zou, Zhili

doi:10.1016/j.pnpbp.2023.110740

Cited by 34 publications

(12 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, our investigation sheds light on several other proteins associated with the regulation of the inflammatory response, such as CREB3L4, CSK, CTSF, CTSS, ICAM5, INHBC, IRF3, ITGAL, and ITGBL1. While prior case-control studies 25 have often identified heightened levels of pro-inflammatory cytokines such as IL-6, IL-8, and IL-1ꞵ in patients with serious mental illness, it is noteworthy that none of these emerged as significant in our analysis, consistent with evidence that medication 26,27 and other state-related factors influence the levels of these biomarkers in patients with serious mental illness. Similarly, prior case-control research has replicably observed elevated blood levels of CRP in individuals with schizophrenia; however, these findings may be state-related 28,29 .…”

Section: Discussionsupporting

confidence: 82%

Large-Scale Mendelian Randomization Study Reveals Circulating Blood-based Proteomic Biomarkers for Psychopathology and Cognitive Task Performance

Bhattacharyya,

John,

Lam

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Research on peripheral (e.g., blood-based) biomarkers for psychiatric illness has typically been low-throughput in terms of both the number of subjects and the range of assays performed. Moreover, traditional case-control studies examining blood-based biomarkers are subject to potential confounds of treatment and other exposures common to patients with psychiatric illnesses. Our research addresses these challenges by leveraging large-scale, high-throughput proteomics data and Mendelian Randomization (MR) to examine the causal impact of circulating proteins on psychiatric phenotypes and cognitive task performance. Methods: We utilized plasma proteomics data from the UK Biobank (3,072 proteins assayed in 34,557 European-ancestry individuals) and deCODE Genetics (4,719 proteins measured across 35,559 Icelandic individuals). Significant proteomic quantitative trait loci (both cis-pQTLs and trans-pQTLs) served as MR instruments, with the most recent GWAS for schizophrenia, bipolar disorder, major depressive disorder, and cognitive task performance (all excluding overlapping UK Biobank participants) as phenotypic outcomes. Results: MR revealed 109 Bonferroni-corrected causal associations (44 novel) involving 88 proteins across the four phenotypes. Several immune-related proteins, including interleukins and complement factors, stood out as pleiotropic across multiple outcome phenotypes. Drug target enrichment analysis identified several novel potential pharmacologic repurposing opportunities, including anti-inflammatory agents for schizophrenia and bipolar disorder and duloxetine for cognitive performance. Conclusions: Identification of causal effects for these circulating proteins suggests potential biomarkers for these conditions and offers insights for developing innovative therapeutic strategies. The findings also indicate substantial evidence for the pleiotropic effects of many proteins across different phenotypes, shedding light on the shared etiology among psychiatric conditions and cognitive ability.

show abstract

Section: Discussionsupporting

confidence: 82%

Large-Scale Mendelian Randomization Study Reveals Circulating Blood-based Proteomic Biomarkers for Psychopathology and Cognitive Task Performance

Bhattacharyya,

John,

Lam

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In the depressive episode, mood and speech activity are reduced speech activity, and symptoms such as fatigue are relieved. Zhang et al [34] observed signi cantly increased levels of pro-in ammatory cytokines, particularly elevated IL-6 levels, in patients with bipolar disorder compared to those in the control group.…”

Section: Discussionmentioning

confidence: 99%

Association of schizophrenia, major depression, and bipolar disorder with sarcopenia-related traits: a bidirectional two-sample Mendelian randomization study

Zhu

Yang²,

Wang³

et al. 2023

Preprint

View full text Add to dashboard Cite

The rising incidence of schizophrenia, depression, bipolar disorder, and other mental illnesses have an association with sarcopenia (SP). Observational studies are susceptible to confounding factors. Mendelian randomization (MR) studies offer a way to mitigate the influence of such factors when assessing causality. The causal connection between schizophrenia, depression, bipolar disorder, and SP was evaluated using inverse-variance weighted (IVW) and other MR methods. Sensitivity analyses were also performed. We found schizophrenia exhibited a negative association with increased whole-body FFM (fat free mass) (odds ratio [OR] = 0.987, 95% CI: 0.979–0.996, P = 0.03), that was attributed to a reduction in FFM in both lower legs (OR = 0.990, 95% CI: 0.981–0.999, P = 0.037; OR = 0.984, 95% CI: 0.975–0.993, P = 0.000). Schizophrenia were negatively correlated in both upper limb, with OR = 0.987, 95% CI: 0.979–0.994, P = 0.001, OR = 0.986, 95% CI: 0.997–0.996, P = 0.004. Major depression and walking pace were negatively related (OR = 0.965, 95% CI: 0.935–0.996, P = 0.027). Bipolar disorder was associated with decreased left leg FFM (OR = 0.979, 95% CI: 0.960–0.999, P = 0.036). Both upper limbs showed a reduction in FFM, with the left and right limbs having an OR = 0.973, 95% CI: 0.953–0.993, P = 0.008 and OR = 0.973, 95% CI: 0.951–0.994, P = 0.014, respectively. Additionally, bipolar disorder was associated with increased walking pace (OR = 1.021, 95% CI: 1.005–1.038, P = 0.012).A potential causal relationship existed among SP-related traits, schizophrenia, and major depression, in addition to bipolar disorder. In conclusion, significant causal relationships exist between schizophrenia, major depression, bipolar disorder, and SP. SP worsens with the increasing severity of mental illness. SP demonstrated a potential causal relationship with schizophrenia and major depression, apart from bipolar disorder.

show abstract

“…The cytokine, macrophage-T lymphocyte, and immune-response system (IRS) theories of MDD summarised these findings (Maes, 1995;Maes et al, 1995a). Recent systematic reviews and meta-analyses corroborate that MDD is associated with elevated serum levels of M1 macrophage and Th1 cytokines and immune activation (Kohler et al, 2017;Zhang et al, 2023;Foley et al, 2023;Gasparini et al, 2022;Mac Giollahui et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviors: effects of in vitro cannabidiol administration

Maes

Rachayon

Jirakran

et al. 2023

Preprint

View full text Add to dashboard Cite

Early flow cytometry studies revealed T cell activation in major depressive disorder (MDD) (Maes et al., 1990-1993). MDD is characterised by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS), including deficits in T regulatory (Treg) cells. This study examines the number of cannabinoid type 1 (CB1) and type 2 (CB2) receptor bearing T/B lymphocytes in MDD, and the effects of in vitro cannabidiol (CBD) administration on CB1/CB2. Using flow cytometry, we determined the percentage of CD20+CB2+, CD3+CB2+, CD4+CB2+, CD8+CB2 and FoxP3+CB1+ cells in 19 healthy controls and 29 MDD patients in 5 conditions: baseline, stimulation with anti-CD3/CD28 with or without 0.1 mug/mL, 1.0 mug/mL or 10.0 mug/mL CBD. We found that CB2+ was significantly higher in CD20+ than CD3+ and CD4+, and CD8+ cells. Stimulation with anti-CD3/CD8 beads increases the number of CB2-bearing CD3+, CD4+, and CD8+ cells, as well as CB1-bearing FoxP3+ cells. There was an inverse association between the number of reduced CD4+CB2+ and IRS profiles, including M1 macrophage, T helper-(Th)-1 and Th-17 phenotypes. MDD is characterized by lowered basal FoxP3+CB1+% and higher CD20+CB2+%. 33.2% of the variance in the depression phenome (including severity of depression, anxiety, and current suicidal behaviors) is explained by CD20+CB2+% (positively) and CD3+CB2+% (inversely). All 5 immune cell populations were significantly increased by 10 mug/mL CBD administration. In conclusion, reductions in FoxP3+CB1+% and CD3+/CD4+CB2+% contribute to deficits in immune homeostasis in MDD, while increased CD20+CB2+% may contribute to the pathophysiology of MDD by activating T-independent humoral immunity.

show abstract

Peripheral cytokine levels across psychiatric disorders: A systematic review and network meta-analysis

Cited by 34 publications

References 47 publications

Large-Scale Mendelian Randomization Study Reveals Circulating Blood-based Proteomic Biomarkers for Psychopathology and Cognitive Task Performance

Large-Scale Mendelian Randomization Study Reveals Circulating Blood-based Proteomic Biomarkers for Psychopathology and Cognitive Task Performance

Association of schizophrenia, major depression, and bipolar disorder with sarcopenia-related traits: a bidirectional two-sample Mendelian randomization study

Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviors: effects of in vitro cannabidiol administration

Contact Info

Product

Resources

About