Suicide attempts are associated with activated immune-inflammatory, nitro-oxidative, and neurotoxic pathways: A systematic review and meta-analysis

Jirakran, Ketsupar; Tunvirachaisakul, Chavit; Maes, Michaël

doi:10.1016/j.jad.2021.08.015

Cited by 55 publications

(47 citation statements)

References 91 publications

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“…SMD values of 0.8, 0.5, and 0.2 indicate large, moderate, and small effect sizes, respectively [40]. Heterogeneity was examined by tau-squared values as mentioned previously and we also computed the Q and I 2 metrics [41,42]. We also used the leave-one-out approach to conduct sensitivity analyses to assess the robustness of the pooled combined meta-analysis effects and betweenstudy heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis

et al. 2022

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Background Coronavirus disease 2019 (COVID-19) is accompanied by activated immune-inflammatory pathways and oxidative stress, which both induce indoleamine-2,3-dioxygenase (IDO), a key enzyme of the tryptophan (TRP) catabolite (TRYCAT) pathway. The aim of this study was to systematically review and meta-analyze the status of the TRYCAT pathway, including the levels of TRP and kynurenine (KYN) and the activity of IDO, as measured by the ratio of KYN/TRP. Methods This systematic review searched PubMed, Google Scholar, and Web of Sciences and included 14 articles that compared TRP and tryptophan catabolites (TRYCATs) in COVID-19 patients versus non-COVID-19 controls, as well as severe/critical versus mild/moderate COVID-19. The analysis was done on a total of 1269 people, including 794 COVID-19 patients and 475 controls. Results The results show a significant (p < 0.0001) increase in the KYN/TRP ratio (standardized mean difference, SMD = 1.099, 95% confidence interval, CI: 0.714; 1.484) and KYN (SMD = 1.123, 95% CI: 0.730; 1.516) and significantly lower TRP (SMD = − 1.002, 95%CI: − 1.738; − 0.266) in COVID-19 versus controls. The KYN/TRP ratio (SMD = 0.945, 95%CI: 0.629; 1.262) and KYN (SMD = 0.806, 95%CI: 0.462; 1.149) were also significantly (p < 0.0001) higher and TRP lower (SMD = − 0.909, 95% CI: − 1.569; − 0.249) in severe/critical versus mild/moderate COVID-19. No significant difference was detected in kynurenic acid (KA) and the KA/KYN ratio between COVID-19 patients and controls. Conclusions Our results indicate increased activity of the IDO enzyme in COVID-19 and severe/critical patients. The TRYCAT pathway is implicated in the pathophysiology and progression of COVID-19 and may signal a worsening outcome of the disease.

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Section: Discussionmentioning

confidence: 99%

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis

et al. 2022

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“…Moreover, the activated IRS pathways in affective disorders are associated with activation of nitro-oxidative pathways with increased reactive oxygen and nitrogen species (RONS), and consequent lipid peroxidation and protein oxidation (Maes, Galecki et al 2011, Maes 2022). Activation of IRS and nitro-oxidative pathways are associated with the key features of affective disorders, including severity of illness, staging (reoccurrence of episodes) and suicidal behaviors including suicidal ideation and attempts (Vasupanrajit, Jirakran et al 2021, Maes 2022, Maes, Rachayon et al 2022). The current theory is that the neurotoxic effects of M1 and Th-1 cytokines and RONS cause neuro-affective toxicity with dysfunctions in brain connectome pathways that lead to staging and the phenome of MDD/BD (Maes 2022, Maes, Rachayon et al 2022).…”

Section: Introductionmentioning

confidence: 99%

The tryptophan catabolite or kynurenine pathway in major depressive and bipolar disorder: a systematic review and meta-analysis

Almulla

Thipakorn

Maes

et al. 2022

Preprint

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Background: There is now evidence that affective disorders including major depressive disorder (MDD) and bipolar disorder (BD) are mediated by immune-inflammatory and nitro-oxidative pathways. Activation of these pathways may be associated with activation of the tryptophan catabolite (TRYCAT) pathway leading to depletion of tryptophan (TRP) and increases in tryptophan catabolites (TRYCATs). Aims: To systematically review and meta-analyze TRP, its competing amino-acids (CAAs) and TRYCAT data in MDD and BD. Methods: This review searched PubMed, Google Scholar and SciFinder and included 121 full-text articles and 15470 individuals, including 8024 MDD/BD patients and 7446 healthy controls. Results: TRP levels (either free and total) and the TRP/CAAs ratio were significantly decreased (p<0.0001) in MDD/BD as compared with controls with a moderate effect size (standardized mean difference for TRP: SMD=-0.513, 95% confidence interval, CI: -0.611; -0.414; and TRP/CAAs: SMD=-0.558, CI: -0.758; -0.358). Kynurenine (KYN) levels were significantly decreased in patients as compared with controls with a small effect size (p<0.0001, SMD= -0.213, 95%CI: -0.295; -0.131). These differences were significant in plasma (p<0.0001, SMD=-0.304, 95%CI: -0.415, -0.194) but not in serum (p=0.054) or the central nervous system (CNS, p=0.771). The KYN/TRP ratio, frequently used as an index of indoleamine-dioxygenase (IDO) activity, and neurotoxicity indices based on downstream TRYCATs were unaltered or even lowered in MDD/BD. Conclusions: Our findings revealed that MDD/BD are accompanied by TRP depletion without IDO and TRYCAT pathway activation. Lowered TRP availability is probably the consequence of lowered serum albumin during the inflammatory response in affective disorders.

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“…Clinical studies have demonstrated a direct association between concentrations of MDA in the plasma with the severity of depressive symptoms [ 40 ]. In this respect, researchers reported that major depressive disorder is associated with a decrease in antioxidant status and induction of oxidative and nitrosative pathways [ 6 , 41 , 42 ]. It has been well-determined that reduced antioxidant capacity is associated with increased MDA levels [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Possible involvement of l-arginine-nitric oxide pathway in the antidepressant activity of Auraptene in mice

et al. 2022

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Background Depression is one of the most common mental illnesses worldwide. Nitric oxide (NO) is involved in the pathophysiology of depression. Auraptene (a coumarin derivative) has been shown to possess pharmacological effects on neurological diseases. Purpose The present study aimed to investigate the possible role of the NO pathway in Auraptene antidepressant effects in male mice. Methods Behavioral tests were used to assess depression-like behaviors. The mice received Auraptene at 10, 30, and 100 mg/kg, the combination of the sub-effective (ineffective) dose of Auraptene (10 mg/kg) and L-NAME, and the combination of the effective dose of Auraptene (30 mg/kg) and L-arginine. Finally, OFT, TST, FST, brain, serum MDA level, antioxidant capacity, hippocampus, and serum NO level were measured. Results The data analysis showed that Auraptene (30 mg/kg) improved depression-like behaviors. Auraptene (30 mg/kg) also significantly reduced serum NO levels (P < 0.05) and significantly increased serum MDA (10 mg/kg, P < 0.05). Auraptene at 30 mg/kg also increased serum antioxidant capacity (P < 0.01). Co-administration of L-NAME and the sub-effective dose of Auraptene enhanced the effects of Auraptene. However, co-administration of the effective dose of Auraptene and L-arginine reduced the impacts of Auraptene. Conclusions The results showed that Auraptene causes antidepressant effects in a dose-dependent manner and acts as a prooxidant at 100 mg/kg, and exacerbates oxidative stress. The antidepressant effects of this active molecule are exerted by reducing the NO level in the hippocampus and serum, increasing the antioxidant capacity, and reducing the MDA level in the serum.

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Suicide attempts are associated with activated immune-inflammatory, nitro-oxidative, and neurotoxic pathways: A systematic review and meta-analysis

Cited by 55 publications

References 91 publications

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis

The tryptophan catabolite or kynurenine pathway in major depressive and bipolar disorder: a systematic review and meta-analysis

Possible involvement of l-arginine-nitric oxide pathway in the antidepressant activity of Auraptene in mice

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