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

Cathomas, Flurin; Guetter, Karoline; Seifritz, Erich; Klaus, Federica; Kaiser, Stefan

doi:10.1038/s41598-021-89335-9

Cited by 25 publications

(13 citation statements)

References 81 publications

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“…Studies investigating the link between QUIN and cognitive deficits in psychiatric diseases are scare, although its level is increased in various cognitive disorders such as dementia, which is also characterized by an inflammatory component [ 36 ], Alzheimer’s disease [ 37 ] and Huntington’s disease [ 38 ]. Interestingly, a study found that more severe cognitive impairments in schizophrenic patients were correlated to increased plasma levels of quinolinic acid [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Alterations of kynurenine pathway in alcohol use disorder and abstinence: a link with gut microbiota, peripheral inflammation and psychological symptoms

et al. 2021

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The gut-brain communication is mostly driven by the immune, metabolic and neural pathways which remained poorly explored in patients with alcohol use disorder (AUD). The metabolites arising from the tryptophan-kynurenine pathway have gained considerable attention since they are at the interface between intestinal bacteria, host immune response and brain functions. This study described the circulating levels of kynurenine metabolites in AUD patients, at the onset (T1) and end (T2) of a 3-week detoxification program, and tested correlations between those metabolites and inflammatory markers, the gut microbiota and the psychological symptoms. Increased concentration of the neurotoxic metabolite quinolinic acid (QUIN) and decreased levels of the neuroprotector metabolite kynurenic acid (KYNA) which both modulate glutamatergic neurotransmission were observed in AUD patients, particularly at T2. The inflammatory marker hsCRP was associated with several metabolic ratios of the kynurenine pathway. Tryptophan, KYNA and QUIN were correlated with depression, alcohol craving and reaction time, respectively. Analysis of gut microbiota revealed that bacteria known as short-chain fatty acid producers, as well as bacterial metabolites including butyrate and medium-chain fatty acids were associated with some metabolites of the tryptophan-kynurenine pathway. Targeting the glutamatergic neurotransmission through the modulation of the kynurenine pathway, by manipulating the gut microbiota, might represent an interesting alternative for modulating alcohol-related behavior.

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Section: Discussionmentioning

confidence: 99%

Alterations of kynurenine pathway in alcohol use disorder and abstinence: a link with gut microbiota, peripheral inflammation and psychological symptoms

et al. 2021

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“…Kynurenine is a catabolic product of the tryptophan-kynurenine metabolism and it is further metabolized into kynurenic acid or quinolinic acid. Previous studies have reported higher levels of plasma kynurenine to be associated with anxiety [57] and higher plasma levels of quinolinic acid associated with depression [58, 59]. The gut microbial pathway involved in p-cresol synthesis (MGB015) was strongly associated with a less than average improvement in depression intensity.…”

Section: Discussionmentioning

confidence: 99%

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures

Pedroso¹,

Kumbhare²,

Joshi³

et al. 2022

Preprint

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BackgroundMental health diseases are a major component of morbidity and health care costs. Obesity and gut disorders are comorbid with mental health, with the gut microbiome hypothesized to play a key mechanistic role in linking them. Pharmacological and behavioral interventions are currently used to treat mental health disorders, but they have limited efficacy. Dietary and weight-loss interventions have been shown to provide different benefits. Still, there exists conflicting evidence regarding their effects which may be due to an individual’s genetic or microbiome factors modulating the improvement of symptoms.ObjectiveWe aimed to identify genetic and gut microbiome factors that explain the improvement in mental health after a dietary and lifestyle intervention for weight loss.MethodsWe recruited 369 individuals participating in the Digbi Health personalized digital care program, for which we evaluated the association between 23 genetic scores, the abundance of 178 gut microbiome genera, and 42 gut-brain modules (pathways related to neuroactive metabolites produced by gut microbes) with the presence/absence of anxiety/depression or sleep problems at baseline and improvement on anxiety, depression, and insomnia after losing at least 2% body weight.ResultsThe mean BMI and age of the study cohort were 34.6 and 48.7, respectively, and there was an overrepresentation of individuals with functional gastrointestinal disorders (84%). On average, the individuals lost 5.4% of body weight at the time of follow-up (mean of 88 days), and more than 95% reported improvement in at least one outcome. We found significant correlations between genetic scores with anxiety and depression at baseline, gut microbial functions with sleep problems at baseline, and genetic scores and gut microbial taxa and functions with anxiety, depression, and insomnia improvement. Among the gut microbial functions identified, the abundance of butyrate synthesis genes was associated with less than average improvement in depression symptoms, the abundance of kynurenine synthesis genes was associated with less than average improvement in anxiety symptoms, and the abundance of genes able to synthesize and degrade neuroactive hormones like nitric oxide was associated with greater than average improvement in depression and insomnia symptoms. Among the genetic scores identified, anxiety or depression at baseline were associated with genetic scores for alcohol use disorder and major depressive disorder, and greater than average improvement in anxiety and depression symptoms was associated with an obstructive sleep apnea genetic score. Furthermore, a type 1 diabetes genetic score was associated with a greater than average improvement of insomnia symptoms, whereas a type 2 diabetes genetic score was associated with a less than average improvement of insomnia symptoms. We compared the relative ability of demographic, genetic, and microbiome factors to explain baseline and improvement in mental health and found that genetic and microbiome factors provide value above demographic variables alone. Medication and recreational drug use do not confound microbiome associations with mental health.ConclusionsThe digital therapeutics care program significantly decreased body weight and concomitantly decreased self-reported mental health symptom intensity. Our results provide evidence that genetic and gut microbiome factors help explain interindividual differences in mental health improvement after dietary and lifestyle interventions for weight loss. Thus, individual genetic and gut microbiome factors provide a basis for designing and further personalizing dietary interventions to improve mental health.

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“…We have previously published findings on task-based explorative behavior in a population of patients with SZ partially overlapping with the current sample 66 – 69 , which used some of the same inflammation measures in the SZ population 70 . In the current publication, we specifically compare additionally inflammatory markers of MDD patients with SZ patients to assess specificity to individual disease.…”

Section: Methodsmentioning

confidence: 97%

Common and disorder-specific upregulation of the inflammatory markers TRAIL and CCL20 in depression and schizophrenia

Klaus

Guetter

Schlegel

et al. 2021

Sci Rep

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Schizophrenia (SZ) and major depressive disorder (MDD) are severe mental disorders, which have been associated with alterations of the peripheral inflammatory network. However, studies for both disorders have not been fully consistent and have focused on few canonical markers with high relevance to the innate immune system, while the role of the adaptive immune system is studied less. Furthermore, it is unclear to what extent inflammatory abnormalities are diagnosis-specific or transdiagnostic. The purpose of this study was to investigate 75 peripheral inflammatory markers including the acute phase protein high-sensitivity C-reactive protein (hsCRP) in patients with MDD (n = 37), SZ (n = 42) and healthy controls (HC) (n = 17), while considering possible confounders and correcting rigorously for multiple testing in group comparisons. We identified C–C chemokine ligand 20 (CCL20) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as the inflammatory markers with significant group differences after controlling for multiple comparisons and adjusting for BMI, sex and smoking as confounders. TRAIL was elevated in both MDD and SZ compared to HC. CCL20 was specifically increased in SZ compared to MDD and HC. There were no significant group differences in hsCRP after correcting for multiple testing. Finally, we observed no significant correlations among CCL20, TRAIL and CRP. TRAIL is a transdiagnostic marker for SZ and MDD, with both markers being independent from CRP and body mass index (BMI). CCL20 may be a novel and specific biomarker of schizophrenia, but an influence of antipsychotic medication cannot be excluded. Identifying novel markers in mental disease bears the potential for future research towards novel treatment strategies by modifying inflammation-related processes.

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

Cited by 25 publications

References 81 publications

Alterations of kynurenine pathway in alcohol use disorder and abstinence: a link with gut microbiota, peripheral inflammation and psychological symptoms

Alterations of kynurenine pathway in alcohol use disorder and abstinence: a link with gut microbiota, peripheral inflammation and psychological symptoms

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures

Common and disorder-specific upregulation of the inflammatory markers TRAIL and CCL20 in depression and schizophrenia

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