Genetic and Epigenetic Factors Influencing Methamphetamine Addiction and Aggressive Behavior among Iraqi Adult men

Abstract

BackgroundMethamphetamine addiction remains a significant public health concern, primarily affecting the central nervous system by disrupting dopamine and serotonin signaling. Epigenetic modifications, especially DNA methylation in the catechol-O-methyltransferase (COMT) and serotonin transporter (SLC6A4) genes, are implicated in addiction-related behavioral changes. While previous research has examined these genes, this study provides a novel perspective by analyzing methylation patterns in relation to aggression subtypes and methamphetamine use behaviors within a Middle Eastern cohort--an underrepresented population in addiction genetics. AimsTo investigate the genetic and epigenetic factors associated with methamphetamine addiction and aggression, with a specific focus on methylation profiles of the SLC6A4 and COMT genes. MethodsSixty male patients with methamphetamine addiction and aggression, and thirty age-matched healthy controls were enrolled. Peripheral blood samples were collected for RNA and DNA extraction. Methylation levels were assessed via bisulfite sequencing, and gene expression was evaluated using qRT-PCR. Behavioral data and substance use patterns were recorded through structured assessments. ResultsPatients showed significantly higher methylation levels in the SLC6A4 (63.29% vs. 7.84%, p = 0.0001) and COMT(50.98% vs. 19.77%, p = 0.0001) genes compared to controls. A strong correlation was observed between dopamine and methamphetamine levels (r = 0.846, p < 0.001). Methylation levels varied by aggression subtype and drug use frequency, suggesting epigenetic involvement in addiction severity and behavioral traits. ConclusionsThis study supports the role of SLC6A4 and COMT gene methylation in methamphetamine addiction and aggression. While causality cannot be inferred, the findings encourage further investigation into epigenetic biomarkers for behavioral risk profiling. Broader, longitudinal studies are needed to evaluate therapeutic potential and inform ethically sound applications in personalized addiction treatment.