Peripheral molecular and brain structural profile implicated stress activation and hyperoxidation in methamphetamine use disorder.

Aim: Methamphetamine use disorders (MUDs) cause widespread disruptions in metabolomic and immunologic processes, highlighting the need for new therapeutic approaches. The purpose of this study was to find molecular and neuroimaging biomarkers for methamphetamine addiction.

Methods: In this study, we recruited 231 patients with MUD at varying stages of withdrawal and 40 healthy controls to quantify the blood levels of 52 molecules using enzyme-linked immunosorbent assay.

Results: The overall molecular disruption caused by methamphetamine was inversely related to withdrawal time (P = 0.0008), with partial recovery observed after 1 year of follow-up (P = 2.20 × 10^-5). Molecules related to stress, immune activation, oxidative products, and cardiac injury were significantly elevated in all MUD groups, while antioxidation enzymes were downregulated. Additionally, the blood level of brain-derived neurotrophic factor was significantly correlated with gray matter volumes in nine brain regions (fusiform gyrus, orbitofrontal cortex, temporal pole, caudate, cerebellum crus, and vermis, adjusted P < 0.05) among patients with MUD.

Conclusion: These findings suggest that patients with MUD exhibit elevated levels of immune response, stress, and oxidative stress, which are associated with brain structural abnormalities.