Abstract
Substance use disorders (SUD) have long been diagnosed and monitored through subjective self-report, leaving a critical gap in objective biomarkers for subtyping, treatment response, and relapse prediction. Cao et al. provided pivotal genetic evidence for bidirectional causal relationships between addiction phenotypes and systemic inflammation using Mendelian Randomization (MR), a methodological breakthrough that opens a tangible path toward closing this gap. Building upon these genetic insights, this commentary evaluates their implications for psychiatric practice and mechanistic research. We assess cytokines such as HGF, IL-10, and M-CSF as potential biomarkers for addiction subtyping, treatment response, and relapse monitoring, and emphasize the need to shift from peripheral measures to central neuroimmune mechanisms. By incorporating the key bibliometric theme of “oxidative stress,” we outline an integrative pathology framework connecting oxidative stress, inflammation, and neuroplasticity in addiction. Methodological considerations of the MR design, including population generalizability, are discussed. We conclude that addiction is not solely a brain disorder but an immunologically embedded condition, and call for trans-ethnic, longitudinal, and multi-omics studies to translate these causal clues into precision diagnostics and immunomodulatory therapies for SUD.
Keywords
Substance use disorders, Addiction, Inflammation, Biomarkers, Mendelian randomization, Oxidative stress