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JAMA Psychiatry. 2014 Jul 1;71(7):761-8. doi: 10.1001/jamapsychiatry.2014.243.

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

Author information

1
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore.

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 (ρ = 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.

PMID:
24806441
PMCID:
PMC4219570
DOI:
10.1001/jamapsychiatry.2014.243
[Indexed for MEDLINE]
Free PMC Article

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