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

Almulla, Abbas F.; Thipakorn, Yanin; Vasupanrajit, Asara; Algon, Ali Abbas Abo; Tunvirachaisakul, Chavit; Aljanabi, Ashwan Abdulzahra Hashim; Oxenkrug, Gregory F.; Al‐Hakeim, Hussein Kadhem; Maes, Michaël

doi:10.1016/j.bbih.2022.100537

Cited by 30 publications

(31 citation statements)

References 192 publications

(171 reference statements)

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“…The findings of the current study should be interpreted in light of its limitations. First, the results would be more interesting if we had assessed biomarkers of chlorinative stress—namely, chlorotyrosine and dichlorotyrosine—and the activation of the tryptophan catabolite (TRYCAT) pathway, which may increase TRYCATs and lower the availability of tryptophan, the precursor of 5-HT [ 103 , 104 ]. Moreover, our COVID-19 studies were conducted on Iraqi patients and, therefore, require replication in other countries.…”

Section: Discussionmentioning

confidence: 99%

Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro-Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection

Al‐Hakeim

Al-Rubaye²,

Almulla

et al. 2023

JCM

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Background: Long-term coronavirus disease 2019 (long COVID) is associated with physio-somatic (chronic fatigue syndrome and somatic symptoms) and affective (depression and anxiety) symptoms. The severity of the long COVID physio-affective phenome is largely predicted by increased peak body temperature (BT) and lowered oxygen saturation (SpO2) during the acute infectious phase. This study aims to delineate whether the association of BT and SpO2 during the acute phase and the long COVID physio-affective phenome is mediated by neurotoxicity (NT) resulting from activated immune-inflammatory and oxidative stress pathways. Methods: We recruited 86 patients with long COVID (3–4 months after the acute phase) and 39 healthy controls and assessed serum C-reactive protein (CRP), caspase 1, interleukin (IL) 1β, IL-18, IL-10, myeloperoxidase (MPO), advanced oxidation protein products (AOPPs), total antioxidant capacity (TAC), and calcium (Ca), as well as peak BT and SpO2 during the acute phase. Results: Cluster analysis revealed that a significant part (34.9%) of long COVID patients (n = 30) show a highly elevated NT index as computed based on IL-1β, IL-18, caspase 1, CRP, MPO, and AOPPs. Partial least squares analysis showed that 61.6% of the variance in the physio-affective phenome of long COVID could be explained by the NT index, lowered Ca, and peak BT/SpO2 in the acute phase and prior vaccinations with AstraZeneca or Pfizer. The most important predictors of the physio-affective phenome are Ca, CRP, IL-1β, AOPPs, and MPO. Conclusion: The infection–immune–inflammatory core of acute COVID-19 strongly predicts the development of physio-affective symptoms 3–4 months later, and these effects are partly mediated by neuro-immune and neuro-oxidative pathways.

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Section: Discussionmentioning

confidence: 99%

Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro-Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection

Al‐Hakeim

Al-Rubaye²,

Almulla

et al. 2023

JCM

Self Cite

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“…Finally, several potential limitations should be mentioned. Because Trp and fatty acids metabolism is greatly affected by individuals, such as gender, age, eating habits, and smoking [ 7 , 68 ], the recruited cases are relatively small and the results still need a large sample to explore further. Meanwhile, considering that antidepressant and antipsychotic drugs could affect Trp and fatty acids metabolism [ 69 , 70 , 71 ], the influence of drugs on plasma Trp metabolites and the composition of fatty acids cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

A Preliminary Comparison of Plasma Tryptophan Metabolites and Medium- and Long-Chain Fatty Acids in Adult Patients with Major Depressive Disorder and Schizophrenia

Liu

Li³

et al. 2023

Medicina

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Background and Objectives: Disturbance of tryptophan (Trp) and fatty acid (FA) metabolism plays a role in the pathogenesis of psychiatric disorders. However, quantitative analysis and comparison of plasma Trp metabolites and medium- and long-chain fatty acids (MCFAs and LCFAs) in adult patients with major depressive disorder (MDD) and schizophrenia (SCH) are limited. Materials and Methods: Clinical symptoms were assessed and the level of Trp metabolites and MCFAs and LCFAs for plasma samples from patients with MDD (n = 24) or SCH (n = 22) and healthy controls (HC, n = 23) were obtained and analyzed. Results: We observed changes in Trp metabolites and MCFAs and LCFAs with MDD and SCH and found that Trp and its metabolites, such as N-formyl-kynurenine (NKY), 5-hydroxyindole-3-acetic acid (5-HIAA), and indole, as well as omega-3 polyunsaturated fatty acids (N3) and the ratio of N3 to omega-6 polyunsaturated fatty acids (N3: N6), decreased in both MDD and SCH patients. Meanwhile, levels of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) decreased in SCH patients, and there was a significant difference in the composition of MCFAs and LCFAs between MDD and SCH patients. Moreover, the top 10 differential molecules could distinguish the two groups of diseases from HC and each other with high reliability. Conclusions: This study provides a further understanding of dysfunctional Trp and FA metabolism in adult patients with SCH or MDD and might develop combinatorial classifiers to distinguish between these disorders.

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“…Tryptophan is an essential amino acid which cannot be produced in the body and its availability to the brain from blood is a rate-limiting step in the production of brain serotonin. Sampling peripheral plasma tryptophan in humans is straightforward and three meta-analyses have concluded that plasma tryptophan is decreased in unmedicated depressed patients, with effect sizes increasing from Hedge's g = 0.45 in all patients to 0.84 in unmedicated patients (Ogawa et al, 2014), a subsequent meta-analysis finding similar effect sizes in major depressive disorder (MDD) patients (Standardised Mean Difference (SMD) = −0.46) (Pu et al, 2021), and recent replication (SMD = −0.51) (Almulla et al, 2022).…”

Section: Plasma Tryptophan In Depressionmentioning

confidence: 99%

Fifty years on: Serotonin and depression

2023

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

Cited by 30 publications

References 192 publications

Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro-Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection

Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro-Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection

A Preliminary Comparison of Plasma Tryptophan Metabolites and Medium- and Long-Chain Fatty Acids in Adult Patients with Major Depressive Disorder and Schizophrenia

Fifty years on: Serotonin and depression

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