장준환 유소영 박예은 지미정 박현미 백지현 이지윤 김대진 이지은 최정석 2024-01-12T03:31:45Z 2024-01-12T03:31:45Z 2022-04-11 2022-04 1663-9812 https://pubs.kist.re.kr/handle/201004/76758 Stress plays an important role in the pathophysiology of addictive disorders. The kynurenine (KYN) pathway involved in neuroimmune and cognitive functions is activated under stress. However, the neuroimmunological-neurocognitive mechanisms in the role of stress in addictive disorders are unclear still now. Ninety-nine young adults aged 18-35 years [alcohol use disorder (AUD), N = 30; Internet gaming disorder (IGD), N = 34; healthy controls (HCs), N = 35] participated in this study. Stress levels, resilience, addiction severity, and neurocognitive functions were evaluated, and serum levels of tryptophan (TRP), 5-hydroxytryptamine (5-HT), KYN, and kynurenine acid (KYNA) were determined using liquid chromatography coupled with tandem mass spectrometry through blood samples. Both addictive disorder groups showed higher levels of stress, lower resilience, and impaired executive functions compared to the HC group. Importantly, the AUD group revealed significantly increased KYN levels and KYN/TRP ratios, as well as decreased KYNA levels and KYNA/KYN ratios compared to HCs (p < 0.001, p < 0.001, p = 0.033, and p < 0.001, respectively). The IGD group showed KYN levels and KYNA/KYN ratios intermediate between those of the AUD group and HCs. Furthermore, in the AUD group, the mediating effect of AUD on KYN through stress level was moderated by resilience [index of moderated mediation = -0.557, boot S.E = 0.331, BCa CI (-1.349, -0.081)]. Stress may induce an imbalance in downstream of KYN pathway metabolites, and the KYN/TRP ratio may play as a neuromediator between stress and behavioral changes in both addictive disorders. This study suggests that regulation of the KYN pathway is critical in the pathophysiology of addictive disorders and it may serve as an important target for future treatment modalities. English Frontiers Media S.A. The Kynurenine Pathway and Mediating Role of Stress in Addictive Disorders: A Focus on Alcohol Use Disorder and Internet Gaming Disorder Article 10.3389/fphar.2022.865576 1 Frontiers in Pharmacology, v.13, pp.1 - 11 Frontiers in Pharmacology 13 1 11 Y scie scopus 000791750300001 Pharmacology & Pharmacy Pharmacology & Pharmacy Article DRUG-USE RESILIENCE TRYPTOPHAN INFLAMMATION VULNERABILITY METABOLITES TRANSITION ANXIETY BRAIN internet gaming disorder stress kynurenine pathway executive function addiction alcohol use disorder