The changes in metabolomics profile induced by intermittent theta burst stimulation in major depressive disorder: an exploratory study

Background Recently, there has been an ongoing interest in the mechanism of intermittent theta burst stimulation (iTBS) in major depressive disorder. Studying the metabolite changes induced by iTBS may help to understand the mechanism. Methods Eleven participants with major depressive disorder received 10 days iTBS treatment. Magnetic resonance imaging (MRI) was used to target the region of the left dorsolateral prefrontal cortex (DLPFC) in each participant. We analyzed the effects of iTBS on metabolites using high-throughput profiling and assessed its impact on depressive symptoms. These analyses were considered exploratory, and no correction for multiple comparisons was applied. Results Among the 318 measured metabolites, a significant increase in cystine, asymmetric dimethylarginine (ADMA), 1-methylhistidine, indoleacetic acid (IAA), diethanolamine (DEA), dopa, riboflavin-5′-monophosphate (FMN), and a significant decrease in alphalinolenic acid (ALA), gamma-linolenic acid (GLA), serotonin, linoleic acid (LA) ( p < 0.05) were detected in the patients after iTBS treatment. In Pearson correlation analysis, the plasma levels of LA, FMN and ADMA at baseline were significantly related to the reduction rate of the 17‐item Hamilton Depression Rating Scale and the Patient Health Questionnaire-9 scores ( p < 0.05). Conclusions Our study highlights that LA, FMN, ADMA and their relationship with oxidative stress, may be key factors in the antidepressant efficacy of iTBS.