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

• Published in: Psychopharmacology 2022-01, Vol.239 (1), p.141-152
• Main Authors: Picci, Giorgia, Fishbein, Diana H., VanMeter, John W., Rose, Emma J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adolescents; Biomedical and Life Sciences; Biomedicine; Brain - diagnostic imaging; Brain research; Child; Cortex (cingulate); Data collection; Dopamine D2 receptors; Dopamine receptors; Drug use; Drugs and youth; Female; Genetic aspects; Genetic diversity; Health aspects; Humans; Longitudinal Studies; Magnetic resonance imaging; Male; Neuroanatomy; Neurosciences; Nucleus accumbens; Opioid receptors (type mu); Opioids; Original Investigation; Pharmaceutical Preparations; Pharmacology/Toxicology; Phenotypes; Psychiatry; Putamen; Receptors; Receptors, Dopamine D2 - genetics; Receptors, Opioid, mu - genetics; Reinforcement; Risk factors; Substance-Related Disorders - genetics; Teenagers
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-021-06030-3

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-naïve 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.