Genetic Polymorphisms and Endocrine Pathways Associated with Problematic Digital-Media Use and Gaming Disorder: A Narrative Review

Background: Problematic digital-media use and gaming disorder have emerged as important public health concerns, particularly among adolescents. Along with psychosocial factors, genetic susceptibility and neuroendocrine pathways may contribute to individual vulnerability to problematic digital-media use and gaming-related problems. Objectives: This review aims to summarize current evidence on the genetic polymorphisms and endocrine pathways associated with problematic digital-media use and gaming disorder, with emphasis on dopaminergic reward mechanisms and hypothalamic–pituitary–adrenal (HPA) axis regulation. Methods: A structured literature search was conducted in PubMed/MEDLINE, Scopus, and Google Scholar for studies published up to 30 June 2026. Relevant human studies addressing genetic, epigenetic, endocrine, or related neurobiological mechanisms of problematic digital-media use and gaming-related behaviors were identified and narratively synthesized according to the principal biological pathways examined. Results: The available evidence suggests that genetic variants affecting dopaminergic neurotransmission (DRD2, COMT, DAT1, and DRD4), stress regulation (CRHR1, FKBP5), serotonergic signaling (SLC6A4), sleep-circadian regulation and other pathways (CHRNA4, NTRK3) may increase susceptibility to problematic Internet and gaming use. Excessive digital media exposure has been associated with alterations in dopaminergic signaling, stress and sleep–circadian regulation, including changes in hypothalamic–pituitary–adrenal axis activity, cortisol secretion and melatonin secretion. These alterations may be related to differences in reward processing, sleep, and emotional regulation, as well as to compulsive digital behaviors. Bidirectional associations have also been reported between problematic digital-media use and depression, anxiety disorders, and attention-deficit/hyperactivity disorder (ADHD). Conclusions: Genetic and endocrine factors may contribute to a broader biopsychosocial vulnerability to problematic digital-media use and gaming-related problems. However, current evidence is insufficient to establish individual genetic variants or endocrine measures as clinically actionable biomarkers. Future research should prioritize large, adequately powered longitudinal studies with harmonized phenotypes, objective behavioral measures, genome-wide approaches, and independent replication to clarify the clinical relevance of biological markers and their potential role in risk prediction and personalized intervention.