Evaluation of mitochondrial DNA copy number alterations and their clinical correlates in methamphetamine use disorder

This study aimed to compare peripheral blood mitochondrial DNA (mtDNA) copy number between patients with methamphetamine use disorder (MUD) and healthy controls, and to examine its associations with clinical characteristics and symptom severity. Fifty-two patients with MUD, diagnosed according to DSM-5 using the SCID-5-CV, and 52 age- and sex-matched healthy controls were included. Clinical features were assessed with validated psychiatric scales, including the Clinical Global Impression-Severity (CGI-S) and Improvement (CGI-I) scales, the Positive and Negative Syndrome Scale (PANSS), and the Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales. Peripheral mtDNA copy number was quantified by quantitative polymerase chain reaction (qPCR). mtDNA copy number was significantly lower in MUD patients compared to controls (p < .001). After adjusting for age and sex, a significant inverse correlation was observed between mtDNA copy number and illness duration (r = -0.312, p = .037). No significant associations were found between mtDNA copy number and psychometric scale scores or clinical characteristics, including history of suicide attempts, self-mutilation, violent behavior, hospitalization, withdrawal symptoms, or drug-induced psychosis (p > .05). In summary, our results indicate a marked decrease in peripheral blood mtDNA copy number among individuals with MUD, along with a significant inverse relationship between mtDNA copy number and the duration of substance use, suggesting cumulative mitochondrial stress associated with chronic methamphetamine exposure.