Effects of OPRM1 and DRD2 on brain structure in drug-naive adolescents: Genetic and neural vulnerabilities to substance use

Genetic variants in the opioid receptor mu 1 (OPRM1) and dopamine receptor d2 (DRD2) genes are implicated in behavioral phenotypes related to substance use disorders (SUD). Despite associations among OPRM1 (rs179971) and DRD2 (rs6277) genes and structural alterations in neural reward pathways implicated in SUDs, little is known about the contribution of risk-related gene variants to structural neurodevelopment. In a 3-year longitudinal study of initially SU-naive adolescents (N=129; 70 females; 11-14 years old), participants underwent an MRI structural scan at baseline and provided genetic assays for OPRM1 and DRD2 with SU behavior assessed during follow-up visits. Baseline differences in key reward-related brain regions (i.e., bilateral caudate and cingulate cortex) were detected in those with genetic liability for SU in OPRM1 who went onto engage in SU at subsequent waves of data collection. In addition, main effects of OPRM1, DRD2, and SU were related to variability in structure of the putamen, anterior cingulate, and nucleus accumbens, respectively. These data provide preliminary evidence that genetic risk factors interact with future SU to confer structural variability prior to SU in regions commonly implicated in risk for SU and the development of SUDs.

Automated summary

Genetic variants in the OPRM1 and DRD2 genes are associated with substance use disorders, affecting structural differences in key reward-related brain regions. The study also found that these genetic risk factors interact with future substance use, leading to structural variability in regions commonly implicated in risk for substance use disorders.