Inflammation and nitro-oxidative stress in current suicidal attempts and current suicidal ideation: a systematic review and meta-analysis

Abstract

A meta-analysis showed a significant association between activated immune-inflammatory and nitro-oxidative (IO&NS) pathways and suicide attempts (SA). There is no data on whether suicidal ideation (SI) is accompanied by activated IO&NS pathways and whether there are differences between SA and SI. The current study searched PubMed, Google Scholar, and Web of Science, for articles published from inception until May 10, 2021, and systematically reviewed and meta-analyzed the association between recent SA/SI (< 3 months) and IO&NS biomarkers. We included studies which compared psychiatric patients with and without SA and SI and controls (either healthy controls or patients without SA or SI) and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence intervals (CI). Our search included 59 studies comprising 4.034 SA/SI cases and 12.377 controls. Patients with SA/SI showed activated IO&NS pathways (SMD: 0.299; CI: 0.200; 0.397) when compared to controls. The immune profiles were more strongly associated with SA than with SI, particularly when compared to healthy controls, as evidenced by activated IO&NS (SMD: 0.796; CI: 0.503; 1.089), immune (SMD: 1.409; CI: 0.637; 1.462), inflammatory (SMD: 1.200; CI: 0.584; 1.816), and neurotoxic (SMD: 0.904; CI: 0.431; 1.378) pathways. The effects sizes of the IO&NS, immune and inflammatory profiles were significantly greater in SA than in SI. In conclusion: increased neurotoxicity due to inflammation and nitro-oxidative stress and lowered neuroprotection explains at least in part why psychiatric patients show increased SA and SI. The IO&NS pathways are more pronounced in recent SA than in SI.

Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are all associated with neurotoxic immune networks and their intricate interactions with metabolic syndrome

“…Most importantly, based on the above we may conclude that the features of OMDD, including neuroticism, cognitive symptoms of depression, suicidal behaviors, and the phenome of OMDD are at least in part mediated via the immunoneurotoxic effects of different cytokines, chemokine, and growth factors. Previously, it was shown that in different MDD phenotypes, suicidal behaviors and the pure cognitive symptoms of depression, suicidal ideation and attempts were significantly associated with neuro-immune pathways , Vasupanrajit, Jirakran et al 2022, Maes, Rachayon et al 2023.…”

Immune activation and immune-associated neurotoxicity in Long-COVID: A systematic review and meta-analysis of 82 studies comprising 58 cytokines/chemokines/growth factors

“…For categorizing effect sizes, we used SMD values of 0.80, 0.5, and 0.20 to denote large, moderate, and small effects, respectively, following Cohen's guidelines (Cohen 2013). Heterogeneity was assessed through tau-squared statistics, Q, and I 2 values, a method consistent with previous metaanalyses (Almulla, Supasitthumrong et al 2022, Almulla, Thipakorn et al 2022, Almulla, Vasupanrajit et al 2022, Vasupanrajit, Jirakran et al 2022. Meta-regression was employed to identify factors contributing to heterogeneity.…”

The Tryptophan Catabolite or Kynurenine Pathway’s Role in Major Depression

“…Nevertheless, induction of the TRYCAT pathway in depression is probably not only a consequence of IRS activation but also of increased oxidative stress and increased LPS levels following increased translocation of Gram-negative bacteria [16]. First, there is evidence of increased reactive oxygen (ROS) and nitrogen (RNS) species in depression and suicidal behaviors with increased superoxide, nitric oxide, peroxynitrite, and hydrogen peroxide production [17][18][19]. Such changes not only lead to decreased neurogenesis, neurodegenerative processes, and reduction in brain volume but also to increased staging characteristics as indicated by an increased reoccurrence of illness index (ROI) and suicidal behaviors [19][20][21].…”

“…First, there is evidence of increased reactive oxygen (ROS) and nitrogen (RNS) species in depression and suicidal behaviors with increased superoxide, nitric oxide, peroxynitrite, and hydrogen peroxide production [17][18][19]. Such changes not only lead to decreased neurogenesis, neurodegenerative processes, and reduction in brain volume but also to increased staging characteristics as indicated by an increased reoccurrence of illness index (ROI) and suicidal behaviors [19][20][21]. Second, increased gut permeability or leaky gut may cause increased bacterial translocation and thus increased LPS load in the peripheral blood of patients with depression [16].…”