Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore.
JAMA Psychiatry. 2014 Jul 1;71(7):761-8. doi: 10.1001/jamapsychiatry.2014.243.
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.
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).
Laboratory-based psychological stress challenge.
Quitting the stressful task early was used as a behavioral marker of distress intolerance.
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).
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.
有几条证据将内源性神经调节剂犬尿酸（KYNA）与精神分裂症联系起来。精神分裂症的病理生理学通常与压力有关，而压力在犬尿酸途径的第一步，限速步骤中起着关键的调节作用，该步骤产生 KYNA。
确定 KYNA 的水平是否在心理压力后发生变化，以及这种变化是否与与压力相关的行为有关。
设计、设置和参与者：在 128 名参与者（64 名来自门诊的精神分裂症患者和 64 名来自社区的健康对照者）进行基于实验室的心理压力挑战后，在基线和 2 次时测量唾液样本中的 KYNA 水平。
基于实验室的心理压力挑战。
提前放弃紧张任务被用作痛苦耐受力差的行为标志物。
与健康对照组相比，精神分裂症患者表现出明显更高的痛苦耐受力（P = .003）。患者和对照组在基线和应激任务后 20 分钟之间，唾液 KYNA 水平均显著升高（分别为 6.72nM [0.65nM] 和 8.43nM [1.05nM]；P = .007）。无法忍受心理压力任务并提前退出的患者的 KYNA 水平明显高于能够耐受心理压力源的患者（P = .02）或健康对照组（P = .02）。在痛苦耐受力差的患者中，KYNA 升高与临床症状严重程度显著相关（ρ = 0.64；P = .008）。
精神分裂症患者中更常见的是痛苦耐受力差。具有这种行为表型的患者唾液 KYNA 水平升高。这种与应激反应行为相关的生物标志物可能有助于减少精神分裂症和其他与应激相关的精神疾病的异质性。
