Investigation of the expression of miRNA-146a targetting the TRAF-6 gene in patients with methamphetamine use disorder before and after detoxification

Methamphetamine is the most commonly used illicit drug worldwide after cannabis. Methamphetamine use disorder is a significant disease that leads to considerable morbidity and mortality in society, affecting individuals' occupational functioning, family life, social life, and physical health. In recent years, there has been an increasing interest in neuroinflammation in research investigating the etiopathogenesis of psychiatric disorders. In our study, we investigated the role of microRNA-146a (miRNA-146a), which is thought to have a role in neuroinflammation, in the etiopathogenesis of methamphetamine use disorder. To the best of our knowledge, there is no study in the literature investigating the relationship between miRNA-146a and methamphetamine use disorder. Our study was planned as a prospective matched case-control study. Between March 2022 and December 2022, 30 patients who were admitted for inpatient treatment at Gaziantep University Department of Psychiatry, and tested positive only for methamphetamine in the urine toxic screening test, and diagnosed with methamphetamine use disorder according to DSM-5 diagnostic criteria, without any additional psychiatric or physical illness, were included in the study. As the control group, 30 healthy individuals without any diseases, matched for gender, age, and smoking status, were randomly selected. To exclude comorbid depression in all participants in the study, the Hamilton Depression Rating Scale (HAM-D) was administered. Through a structured interview (SCID-5), the most common comorbidities such as bipolar disorder and attention deficit hyperactivity disorder were excluded, and only individuals diagnosed with methamphetamine use disorder were included in the study. Personality disorders, despite showing a high rate of comorbidity, were not included in the exclusion criteria due to the lack of a significant association with neuroinflammation. Clinical interviews were conducted with the patients, the Penn Substance Craving Scale was administered, and blood samples were taken both before and after the detoxification treatment of methamphetamine to measure the levels of miRNA-146a, which we believe are associated with neuroinflammation. In our study, the expression levels of miRNA-146a in the patient group were found to be significantly lower than those in the healthy control group before detoxification treatment and significantly higher after detoxification treatment. The HAM-D score of the patient group was significantly higher compared to the controls. There was a moderate negative correlation between the amount of daily methamphetamine exposure and the miRNA-146a expression level measured before detoxification treatment. In our study, the significant decrease in miRNA-146a expression levels in the patient group before detoxification treatment and its significant increase after treatment suggest that this parameter may be indicative of neuroinflammation, indicating an important role of methamphetamine in neuroinflammation. After further elucidating the relationship between miRNA-146a expression levels and methamphetamine use disorder, new treatment strategies associated with miRNA-146a can be developed. The positive correlation between the duration of methamphetamine exposure and miRNA-146a expression levels measured after detoxification treatment implies that miRNA-146a expression levels could be an important parameter in predicting the prognosis of the disease. We believe that our study will contribute to this field, which has limited data in the literature.