BACKGROUND Gamma-hydroxybutyrate (GHB; or sodium oxybate) is an endogenous GHB-/gamma-aminobutyric acid B receptor agonist. It is approved for application in narcolepsy and has been proposed for the potential treatment of Alzheimer's disease, Parkinson's disease, fibromyalgia, and depression, all of which involve neuro-immunological processes. Tryptophan catabolites (TRYCATs), the cortisol-awakening response (CAR), and brain-derived neurotrophic factor (BDNF) have been suggested as peripheral biomarkers of neuropsychiatric disorders. GHB has been shown to induce a delayed reduction of T helper and natural killer cell counts and alter basal cortisol levels, but GHB's effects on TRYCATs, CAR, and BDNF are unknown. METHODS Therefore, TRYCAT and BDNF serum levels, as well as CAR and the affective state (Positive and Negative Affect Schedule [PANAS]) were measured in the morning after a single nocturnal dose of GHB (50 mg/kg body weight) in 20 healthy male volunteers in a placebo-controlled, balanced, randomized, double-blind, cross-over design. RESULTS In the morning after nocturnal GHB administration, the TRYCATs indolelactic acid, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid; the 3-hydroxykynurenine to kynurenic acid ratio; and the CAR were significantly reduced (P < 0.05-0.001, Benjamini-Hochberg corrected). The quinolinic acid to kynurenic acid ratio was reduced by trend. Serotonin, tryptophan, and BDNF levels, as well as PANAS scores in the morning, remained unchanged after a nocturnal GHB challenge. CONCLUSIONS GHB has post-acute effects on peripheral biomarkers of neuropsychiatric disorders, which might be a model to explain some of its therapeutic effects in disorders involving neuro-immunological pathologies. This study was registered at ClinicalTrials.gov as NCT02342366.

中文翻译：

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夜间γ-羟基丁酸可降低健康志愿者的皮质醇觉醒反应和早期Kynurenine途径代谢产物。

背景技术γ-羟基丁酸酯（GHB；或羟丁酸钠）是内源性GHB- /γ-氨基丁酸B受体激动剂。它被批准用于发作性睡病，并已建议用于潜在的阿尔茨海默氏病，帕金森氏病，纤维肌痛和抑郁症的治疗，所有这些疾病均涉及神经免疫过程。色氨酸分解代谢产物（TRYCATs），皮质醇唤醒反应（CAR）和脑源性神经营养因子（BDNF）已被建议作为神经精神疾病的外周生物标志物。GHB已被证明可诱导T辅助和自然杀伤细胞计数的延迟减少并改变基础皮质醇水平，但GHB对TRYCAT，CAR和BDNF的作用尚不清楚。方法因此，TRYCAT和BDNF血清水平 以及CAR和情绪状态（正面和负面影响表[PANAS]）是在安慰剂对照，平衡的20例健康男性志愿者中，在夜间单剂量服用GHB（50 mg / kg体重）后测量的。 ，随机，双盲，交叉设计。结果夜间服用GHB后的早晨，TRYCATs吲哚乳酸，犬尿氨酸，犬尿酸，3-羟基犬尿氨酸和喹啉酸。3-羟基犬尿氨酸与犬尿酸的比例；和CAR显着降低（P <0.05-0.001，Benjamini-Hochberg校正）。喹啉酸与犬尿酸的比例呈下降趋势。夜间GHB激发后，血清素，色氨酸和BDNF水平以及早晨的PANAS得分保持不变。结论GHB对神经精神疾病的外周生物标志物具有急性后效应，这可能是解释其在涉及神经免疫病理学的疾病中的某些治疗作用的模型。该研究已在ClinicalTrials.gov上注册为NCT02342366。