Dataset Information

A Potential Interface between the Kynurenine Pathway and Autonomic Imbalance in Schizophrenia.

ABSTRACT: Schizophrenia is a neuropsychiatric disorder characterized by various symptoms including autonomic imbalance. These disturbances involve almost all autonomic functions and might contribute to poor medication compliance, worsened quality of life and increased mortality. Therefore, it has a great importance to find a potential therapeutic solution to improve the autonomic disturbances. The altered level of kynurenines (e.g., kynurenic acid), as tryptophan metabolites, is almost the most consistently found biochemical abnormality in schizophrenia. Kynurenic acid influences different types of receptors, most of them involved in the pathophysiology of schizophrenia. Only few data suggest that kynurenines might have effects on multiple autonomic functions. Publications so far have discussed the implication of kynurenines and the alteration of the autonomic nervous system in schizophrenia independently from each other. Thus, the coupling between them has not yet been addressed in schizophrenia, although their direct common points, potential interfaces indicate the consideration of their interaction. The present review gathers autonomic disturbances, the impaired kynurenine pathway in schizophrenia, and the effects of kynurenine pathway on autonomic functions. In the last part of the review, the potential interaction between the two systems in schizophrenia, and the possible therapeutic options are discussed.

SUBMITTER: Buki A

PROVIDER: S-EPMC8467675 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Schizophrenia (SCZ) and bipolar disorder (BD) are associated with immunological dysfunctions that have been hypothesized to lead to clinical symptomatology in particular through kynurenine pathway abnormalities. The aim of this study was thus to investigate the impact of serum kynurenine metabolite levels on diagnosis, clinical state, symptom severity and clinical course in a large French transdiagnostic cohort of SCZ and BD patients. Four patient groups (total n = 507) were included in a cross-sectional observational study: 1) hospitalized acute bipolar patients (n = 205); 2) stable bipolar outpatients (n = 116); 3) hospitalized acute schizophrenia patients (n = 111) and 4) stable schizophrenia outpatients (n = 75), in addition to healthy controls (HC) (n = 185). The quantitative determination of serum kynurenine metabolites was performed using liquid chromatography-tandem mass spectrometry. Kynurenine levels were lower in all patients combined compared to HC while ANCOVA analyses did not reveal inter-diagnostic difference between SCZ and BD. Interestingly, hospitalized patients of both diagnostic groups combined displayed significantly lower kynurenine levels than stabilized outpatients. Psychotic symptoms were associated with lower quinaldic acid (F = 9.18, p=<.001), which is KAT-driven, whereas a longer duration of illness contributed to abnormalities in tryptophan (F = 5.41, p = .023), kynurenine (F = 16.93, p=<.001), xanthurenic acid (F = 9.34, p = .002), quinolinic acid (F = 9.18, p = .003) and picolinic acid (F = 4.15, p = .043), metabolized through the KMO-branch. These data confirm illness state rather than diagnosis to drive KP alterations in SCZ and BD. Lower levels of KP metabolites can thus be viewed as a transdiagnostic feature of SCZ and BD, independently associated with acute symptomatology and a longer duration of illness. Quinaldic acid has seldomly been investigated by previous studies and appears an important state marker in SCZ and BD. As serum samples are used in this study, it is not possible to extrapolate these findings to the brain.

Project description:BackgroundThe cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA).MethodsThis work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by high-performance liquid chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored.ResultsIn the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzyme expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolite content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC.ConclusionsThus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.

Dataset Information

A Potential Interface between the Kynurenine Pathway and Autonomic Imbalance in Schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets