Metabolomics changes after rTMS intervention reveal potential peripheral biomarkers in methamphetamine dependence

Methamphetamine is one of the most commonly used drugs around the world, leading to serious public health and psychiatric problems. Due to the lackness of objective laboratory evaluation indicators, the molecular mechanisms of methamphetamine dependence still remain unclear. Previous evidence demonstrated that repetitive transcranial magnetic stimulation (rTMS) may be useful in treating drug addiction. The aim of this study was to identify and validate plasma metabolomics biomarkers in patients with methamphetamine use disorder before and after rTMS intervention. An untargeted gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) based metabolomics approach was applied to characterize the metabolic profile of forty methamphetamine dependent subjects and thirty-eight healthy controls in peripheral blood mononuclear cells (PBMCs). Patients were randomized to receive either rTMS or sham over the DLPFC for four weeks (20 daily sessions, 900 pulses per day). Cognitive function were assessed before and after rTMS intervention. Eight PBMC metabolites responsible for distinguishing real rTMS from sham treatment were identified. These metabolites were mainly involved in energy metabolism and oxidative stress. Compared with baseline, the expression of three metabolites was reversed after rTMS intervention: alpha-tocopherol, glyceric acid and fumaric acid. Changes of the alpha-tocopherol were associated with cognitive function improvement following rTMS. These findings suggest that energy metabolism and oxidative stress system may be associated with the effect of rTMS on cognitive function in methamphetamine dependence, and warrant further investigation.