Gleissenthall Gabriele V, Geisler Simon, Malik Peter, Kemmler Georg, Benicke Hannah, Fuchs Dietmar, Mechtcheriakov Sergei
Corresponding author: Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Alcohol Alcohol. 2014 May-Jun;49(3):251-5. doi: 10.1093/alcalc/agu011. Epub 2014 Mar 18.
The aim of the study was to investigate the parameters of tryptophan and phenylalanine metabolism and their associations to immune system activation and to behavioural symptoms during medium-term withdrawal (4-12 weeks of abstinence) in alcohol-dependent patients.
Biochemical assays and clinical assessments at the beginning of treatment (fourth week of alcohol abstinence in average) and prior to the discharge after 8 weeks of treatment.
Kynurenine to tryptophan ratio (Kyn/Trp) slightly correlated with neopterin levels in early post-withdrawal period (Week 4 of abstinence) but this association disappeared after 12 weeks of abstinence. Phenylalanine and tyrosine concentrations as well as phenylalanine to tyrosine ratio (Phe/Tyr) decreased between Weeks 4 and 12 of abstinence. Kynurenine and Kyn/Trp increased significantly at 12th week of abstinence when compared with the beginning of the study (Week 4 of abstinence). At Week 12, Kyn/Trp significantly correlated with such behavioural symptoms as fatigue, irritability and sleep disturbances.
Tryptophan breakdown in early stages may be influenced by the increased activity of indoleamine 2,3-dioxygenase but the increase of Kyn/Trp between Weeks 4 and 12 of abstinence seems to be independent of immune changes and correlates with behavioural symptoms in later stages of the post-withdrawal course. A possible role of kynurenine metabolites in mediation of the increased stress sensibility in post-withdrawal alcohol-dependent patients is discussed.
本研究旨在调查酒精依赖患者中期戒断(戒断4 - 12周)期间色氨酸和苯丙氨酸代谢参数及其与免疫系统激活和行为症状的关联。
在治疗开始时(平均戒酒第4周)及治疗8周后出院前进行生化检测和临床评估。
戒断后早期(戒断第4周),犬尿氨酸与色氨酸比值(Kyn/Trp)与新蝶呤水平轻度相关,但戒断12周后这种关联消失。在戒断第4周和第12周之间,苯丙氨酸和酪氨酸浓度以及苯丙氨酸与酪氨酸比值(Phe/Tyr)下降。与研究开始时(戒断第4周)相比,戒断第12周时犬尿氨酸和Kyn/Trp显著增加。在第12周时,Kyn/Trp与疲劳、易怒和睡眠障碍等行为症状显著相关。
早期色氨酸分解可能受吲哚胺2,3 -双加氧酶活性增加的影响,但在戒断第4周和第12周之间Kyn/Trp的增加似乎与免疫变化无关,且与戒断后病程后期的行为症状相关。本文讨论了犬尿氨酸代谢产物在介导戒断后酒精依赖患者应激敏感性增加方面的可能作用。