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Stress-induced increase in kynurenic acid as a potential biomarker for patients with schizophrenia and distress intolerance.

ABSTRACT: IMPORTANCE:Several lines of evidence have linked the endogenous neuromodulator kynurenic acid (KYNA) to schizophrenia. The pathophysiology of schizophrenia is commonly associated with stress, and stress plays a key regulatory role in the first, rate-limiting step of the kynurenine pathway, which produces KYNA. OBJECTIVE:To determine whether the level of KYNA changes following psychological stress and whether this change is associated with stress-related behavior. DESIGN, SETTING, AND PARTICIPANTS:The KYNA level was measured in saliva samples taken at baseline and at 2 times following a laboratory-based psychological stress challenge in 128 participants (64 patients with schizophrenia from outpatient clinics and 64 healthy controls from the community). EXPOSURE:Laboratory-based psychological stress challenge. MAIN OUTCOMES AND MEASURES:Quitting the stressful task early was used as a behavioral marker of distress intolerance. RESULTS:Patients with schizophrenia showed a significantly higher rate of distress intolerance compared with healthy controls (P?=?.003). Salivary KYNA levels increased significantly between baseline and 20 minutes following the stress task in both patients and controls (mean [SEM], 6.72nM [0.65nM] vs 8.43nM [1.05nM], respectively; P?=?.007). Patients who were unable to tolerate the stressful tasks and quit early showed significantly higher levels of KYNA than patients who tolerated the psychological stressor (P?=?.02) or healthy controls (P?=?.02). In patients with distress intolerance, KYNA elevation significantly correlated with the severity of clinical symptoms (??=?0.64; P?=?.008). CONCLUSIONS AND RELEVANCE:Distress intolerance is more common in patients with schizophrenia. Patients with this behavioral phenotype have elevated salivary KYNA levels. This stress response behavior-linked biomarker may aid heterogeneity reduction in schizophrenia and other stress-related psychiatric conditions.

SUBMITTER: Chiappelli J

PROVIDER: S-EPMC4219570 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Stress-induced increase in kynurenic acid as a potential biomarker for patients with schizophrenia and distress intolerance.

Chiappelli Joshua J Pocivavsek Ana A Nugent Katie L KL Notarangelo Francesca M FM Kochunov Peter P Rowland Laura M LM Schwarcz Robert R Hong L Elliot LE

JAMA psychiatry 20140701 7

<h4>Importance</h4>Several lines of evidence have linked the endogenous neuromodulator kynurenic acid (KYNA) to schizophrenia. The pathophysiology of schizophrenia is commonly associated with stress, and stress plays a key regulatory role in the first, rate-limiting step of the kynurenine pathway, which produces KYNA.<h4>Objective</h4>To determine whether the level of KYNA changes following psychological stress and whether this change is associated with stress-related behavior.<h4>Design, settin ...[more]

PMID: 24806441

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Project description:BackgroundDiabetes significantly delays wound healing through oxidative stress, inflammation and impaired re-epithelialization that lead to defective regulation of the healing process, although the related mechanism remains unclear. Here, we aim to investigate the potential role and mechanism for the beneficial effect of betulinic acid (BA) on diabetic wound healing.MethodsThe molecular effect of BA on hyperglycemia-mediated gene expression, oxidative stress, inflammation and glucose uptake was evaluated in endothelial, fibroblast and muscle cells. Burn injury was introduced to streptozotocin-induced diabetic rats and BA administration through either an intraperitoneal (IP) or topical (TOP) technique was used for wound treatment. Glucose tolerance was evaluated in both muscle tissue and fibroblasts, while oxidative stress and inflammation were determined in both the circulatory system and in wound tissues. The effect of BA on the wound healing process was also evaluated.ResultsBA treatment reversed hyperglycemia-induced glucose transporter type 4 (GLUT4) suppression in both muscle and fibroblast cells. This treatment also partly reversed hyperglycemia-mediated suppression of endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and nuclear factor NFκB p65 subunit (NFκB p65) activation in endothelial cells. An in vivo rat study showed that BA administration ameliorated diabetes-mediated glucose intolerance and partly attenuated diabetes-mediated oxidative stress and inflammation in both the circulatory system and wound tissues. BA administration by both IP and TOP techniques significantly accelerated diabetic wound healing, while BA administration by either IP or TOP methods alone had a significantly lower effect.ConclusionsBA treatment ameliorates hyperglycemia-mediated glucose intolerance, endothelial dysfunction, oxidative stress and inflammation. Administration of BA by both IP and TOP techniques was found to significantly accelerate diabetic wound healing, indicating that BA could be a potential therapeutic candidate for diabetic wound healing.

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Stress-induced increase in kynurenic acid as a potential biomarker for patients with schizophrenia and distress intolerance.

Publications

Stress-induced increase in kynurenic acid as a potential biomarker for patients with schizophrenia and distress intolerance.

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