Metabolomics analysis of serum biomarkers and metabolic pathways in addictive disorders: focus on internet gaming disorder and alcohol use disorder

Abstract

Metabolomics technologies provide a means to uncover metabolic disturbances and the associated signaling pathways in addictive disorders such as alcohol use disorder (AUD) and internet gaming disorder (IGD). While it is anticipated that common or distinctive metabolic pathways may be implicated in AUD and IGD groups, there have been few studies of comparative metabolomic analysis for these two addictive disorders. In the current study, we investigated the metabolomic profiles of serum samples obtained from ninety-nine young adults aged 18–35 years, comprising individuals with AUD (n = 30), IGD (n = 34), and healthy controls (HCs, n = 35) using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q TOF-MS). From the metabolomic analysis of the serum samples, 26 metabolites exhibited statistically significant changes (p-value < 0.05, > 1.5-fold change) between individuals with AUD or IGD and HCs. Among these metabolites, six, including N-acetyltryptophan, L-formylkynurenine, and 3,4-dihydroxymandelic acid, exhibited increased or decreased levels in both the AUD and IGD groups compared to HCs. Metabolic pathway analysis revealed that the tyrosine metabolism pathway was specific to both the AUD and IGD groups, whereas sphingolipid metabolism and steroid hormone biosynthesis were activated in the AUD group compared to individuals with IGD and HCs. While the current study is the first attempt to conduct comparative metabolomic analyses of the substance and non-substance-related addictions, the findings will broaden the understanding of the molecular mechanisms underlying addictive behaviors and offer important biomarkers for diagnosing and devising therapeutic strategies for these addictive disorders.