Cross-sectional relationship between kynurenine pathway metabolites and cognitive function in major depressive disorder

Zhou, Yanling; Zheng, Wei; Liu, Weijian; Wang, Chengyu; Zhan, Yongle; Li, Hanqiu; Chen, Lijian; Ning, Yuping

doi:10.1016/j.psyneuen.2018.11.001

Cited by 43 publications

(24 citation statements)

References 44 publications

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“…This is in contrast to a recent study, where Zhou et al reported an association between cognitive impairment and elevated serum KYN levels and the KYN/TRP ratio. However, the authors found this association only in female but not male patients and further, QUIN was not studied 69 . Our study population was not large enough to investigate female and male patients separately and therefore future studies are needed to investigate potential sex differences in TRYCATs and cognitive deficits across neuropsychiatric disorders.…”

Section: Discussionmentioning

confidence: 83%

Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder

Cathomas

Guetter

Seifritz

et al. 2021

Sci Rep

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Tryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD). The relationship to different psychopathological dimensions within these disorders however remains to be elucidated. We thus investigated potential group differences of tryptophan, kynurenine, kynurenic acid, 3-hydroxy kynurenine and quinolinic acid in the plasma of 19 healthy controls (HC), 45 patients with SZ and 43 patients with MDD and correlated plasma proteins with the “motivation and pleasure” dimension and cognition. After correcting for the covariates age, sex, body mass index, smoking and medication, patients with MDD showed lower kynurenine and 3-hydroxy kynurenine levels compared to HC. Quinolinic acid correlated negatively with composite cognitive score in patients with SZ, indicating that more severe cognitive impairments were associated with increased plasma levels of quinolinic acid. No correlations were found in patients with MDD. These results indicate that MDD and SZ are associated with dysregulation of the kynurenine pathway. Quinolinic acid might be specifically implicated in the pathophysiology of cognitive deficits in patients with SZ. Further studies are needed to determine whether TRYCATs are causally involved in the etiology of these neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 83%

Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder

Cathomas

Guetter

Seifritz

et al. 2021

Sci Rep

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“…The etiology of depression is partly attributed to a dysregulated KYN/TRP pathway (Reus et al, 2015). An elevated ratio of plasma KYN/TRP often correlates positively with the depression severity in human (Maes et al, 2002;Gabbay et al, 2010;Baranyi et al, 2013;Zhou et al, 2019). It was demonstrated that L. reuteri intake improved behaviors of depressed mice by reversing the stress-induced (1) decrease in fecal H 2 O 2 levels and Lactobacillus populations, and (2) increase in intestinal IDO1 expression and plasma KYN levels (Marin et al, 2017).…”

Section: Microbial Hydrogen Peroxide and Kynurenine Pathwaymentioning

confidence: 99%

Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential

et al. 2020

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The accumulating knowledge of the host-microbiota interplay gives rise to the microbiota-gut-brain (MGB) axis. The MGB axis depicts the interkingdom communication between the gut microbiota and the brain. This communication process involves the endocrine, immune and neurotransmitters systems. Dysfunction of these systems, along with the presence of gut dysbiosis, have been detected among clinically depressed patients. This implicates the involvement of a maladaptive MGB axis in the pathophysiology of depression. Depression refers to symptoms that characterize major depressive disorder (MDD), a mood disorder with a disease burden that rivals that of heart diseases. The use of probiotics to treat depression has gained attention in recent years, as evidenced by increasing numbers of animal and human studies that have supported the antidepressive efficacy of probiotics. Physiological changes observed in these studies allow for the elucidation of probiotics antidepressive mechanisms, which ultimately aim to restore proper functioning of the MGB axis. However, the understanding of mechanisms does not yet complete the endeavor in applying probiotics to treat MDD. Other challenges remain which include the heterogeneous nature of both the gut microbiota composition and depressive symptoms in the clinical setting. Nevertheless, probiotics offer some advantages over standard pharmaceutical antidepressants, in terms of residual symptoms, side effects and stigma involved. This review outlines antidepressive mechanisms of probiotics based on the currently available literature and discusses therapeutic potentials of probiotics for depression.

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“…Demographic variables (age and gender), clinical assessments (mood state and symptom severity scores), and TRYCAT metabolite levels (means and standard deviations) were extracted from each study. Authors were contacted for additional information when data could not be extracted from the paper; this was received from four papers (13,(23)(24)(25). The Review Manager 5.3 (RevMan 5.3) computer program was used for performing the primary meta-analysis and subgroup analyses.…”

Section: Data Synthesis and Analysismentioning

confidence: 99%

Tryptophan Catabolites in Bipolar Disorder: A Meta-Analysis

et al. 2021

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ObjectiveTryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of TRYCAT levels in bipolar disorder (BD) patients compared to healthy controls.MethodsA systematic literature search in seven electronic databases (PubMed, Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier) was conducted on TRYCAT levels in cerebrospinal fluid or peripheral blood according to the PRISMA statement. A minimum of three studies per TRYCAT was required for inclusion. Standardized mean differences (SMD) were computed using random effect models. Subgroup analyses were performed for BD patients in a different mood state (depressed, manic). The methodological quality of the studies was rated using the modified Newcastle-Ottawa Quality assessment Scale.ResultsTwenty-one eligible studies were identified. Peripheral levels of tryptophan (SMD = -0.44; p < 0.001), kynurenine (SMD = - 0.3; p = 0.001) and kynurenic acid (SMD = -.45; p = < 0.001) were lower in BD patients versus healthy controls. In the only three eligible studies investigating TRP in cerebrospinal fluid, tryptophan was not significantly different between BD and healthy controls. The methodological quality of the studies was moderate. Subgroup analyses revealed no significant difference in TRP and KYN values between manic and depressed BD patients, but these results were based on a limited number of studies.ConclusionThe TRYCAT pathway appears to be downregulated in BD patients. There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs.

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Cross-sectional relationship between kynurenine pathway metabolites and cognitive function in major depressive disorder

Cited by 43 publications

References 44 publications

Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder

Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder

Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential

Tryptophan Catabolites in Bipolar Disorder: A Meta-Analysis

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