The Kynurenine Pathway and Mediating Role of Stress in Addictive Disorders: A Focus on Alcohol Use Disorder and Internet Gaming Disorder

• DOI: 10.3389/fphar.2022.865576
• Publication Date: 2022-04-11T10:31:25Z
• Authors: Joon Hwan Jang; So Young Yoo; Yae Eun Park; Mi-Jung Ji; Hyun-Mee Park; Ji Hyun Back; Ji Yoon Lee; Dai Jin Kim; Ji Eun Lee; Jung-Seok Choi
• Keywords: Alcohol use disorder; Kynurenine pathway

Stress plays an important role in the pathophysiology of addictive disorders. The kynurenine (KYN) pathway involved neuroimmune and cognitive functions is activated under stress. However, neuroimmunological-neurocognitive mechanisms stress disorders are unclear still now. Ninety-nine young adults aged 18-35 years [alcohol use disorder (AUD), N = 30; Internet gaming (IGD), 34; healthy controls (HCs), 35] participated this study. levels, resilience, addiction severity, neurocognitive were evaluated, serum levels tryptophan (TRP), 5-hydroxytryptamine (5-HT), KYN, acid (KYNA) determined using liquid chromatography coupled with tandem mass spectrometry through blood samples. Both groups showed higher stress, lower impaired executive compared to HC group. Importantly, AUD group revealed significantly increased KYN KYN/TRP ratios, as well decreased KYNA KYNA/KYN ratios HCs (p < 0.001, p 0.033, respectively). IGD intermediate between those HCs. Furthermore, group, mediating effect on level was moderated by resilience [index mediation -0.557, boot S.E 0.331, BCa CI (-1.349, -0.081)]. may induce imbalance downstream metabolites, ratio play a neuromediator behavioral changes both This study suggests that regulation critical it serve target for future treatment modalities.