title: Stress-induced increase in kynurenic acid as a potential biomarker for patients with schizophrenia and distress intolerance.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  Laboratory-based psychological stress challenge.
  
  
  METHODS
  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 (ρ = 0.64; P = .008).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore.
authors.forename: Joshua
authors.initials: J
authors.lastname: Chiappelli
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore.
authors.forename: Ana
authors.initials: A
authors.lastname: Pocivavsek
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Nugent
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore.
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Notarangelo
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore.
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Rowland
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore.
authors.forename: Robert
authors.initials: R
authors.lastname: Schwarcz
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D007736:Kynurenic Acid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000502:physiology; D012463:Saliva / Q000737:chemistry / Q000502:physiology; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D018377:Neurotransmitter Agents; D007736:Kynurenic Acid