We identified one differentially methylated region in DRD4, which survived genome-wide correction, associated with physical aggression above and beyond co-occurring symptomatology (e.g., ADHD, substance use), and showed strong cross-tissue concordance with both blood and brain.
Polymorphisms across serotonergic (SLC6A4, 5-HTTLPR), dopaminergic (DRD4, u-VNTR), noradrenergic (SLC6A2, rs36021), and GABAergic (GABRA2, rs279858; GABRA6, rs3811995) genes were examined given prior support for associations with temperament, externalizing behavior, and substance use problems.
Male adolescents who carried at least one allele of DRD4 with 7 or more repeats who were assigned to the control condition evinced more substance use across 22 months than did (a) carriers of at least one allele of DRD4 with 7 or more repeats who were assigned to SAAF-T or (b) adolescents assigned to either condition who carried two alleles of DRD4 with 6 or fewer repeats.
Genetic studies independently link the DRD4 gene polymorphism to substance use and to internalizing disorders, but no study has examined whether the DRD4 polymorphism is linked to comorbid marijuana use and depression in a population sample.
Supporting the differential susceptibility to parenting hypothesis, the results suggest a greater preventive effect for youths carrying a 7-repeat allele, a role for DRD4 in the escalation of substance use during adolescence, and potential for an enhanced understanding of early-onset substance use.
It is unclear whether the DRD4 gene is a marker for an underlying propensity for greater urge or whether the DRD4 gene differentially moderates the neuroadaptive effects of extended substance use on urge.
The inclusion of the 5-HTTLPR genotype provided greater precision to the relationships in that higher residential instability, in conjunction with the risk variant of 5-HTTLPR (i.e., the short allele), was associated with the highest level and steepest gradient of growth in substance use across ages 10-24 years.
Polymorphisms across serotonergic (SLC6A4, 5-HTTLPR), dopaminergic (DRD4, u-VNTR), noradrenergic (SLC6A2, rs36021), and GABAergic (GABRA2, rs279858; GABRA6, rs3811995) genes were examined given prior support for associations with temperament, externalizing behavior, and substance use problems.
Effects of the serotonin transporter (5-HTTLPR) and α2A-adrenoceptor (C-1291G) genotypes on substance use in children and adolescents: a longitudinal study.
A genetic vulnerability factor, a variable nucleotide repeat polymorphism (VNTR) in the promoter region of the serotonin transporter gene SLC6A4, known as 5-HTTLPR, was hypothesized to moderate the link between substance use at age 14 and risky sexual behavior at age 16.
Latent growth curve modeling indicated that 5-HTTLPR status (presence of 1 or 2 copies of the s allele) was linked with increases in substance use over time; however, this association was greatly reduced when youths received high levels of involved-supportive parenting.
In the present study, five diallelic sites spanning the DRD2 gene were determined in combined Caucasian (non-Hispanic) studies of more severe alcoholics (n = 92) and controls screened for substance use (n = 85).
In conclusion, the severity of alcohol dependence in alcoholics and of substance use behaviors in controls are important variables in DRD2 allelic association.
The present study used a daily monitoring method that assessed the effects of GABRA2 variation on substance use as it occurred in the natural environment during emerging adulthood.
The inverse association between parental education and substance use was statistically mediated by each element of diminished alternative reinforcement at Wave 2.
In the fully adjusted models, continued smoking at Wave 2 among Wave 1 smokers was associated with significantly greater odds of substance use (OR = 1.56, 95% CI, 1.10-2.20) and SUD relapse (OR = 2.02, 95% CI, 1.65-2.47) compared to Wave 2 nonsmoking.
Polymorphisms across serotonergic (SLC6A4, 5-HTTLPR), dopaminergic (DRD4, u-VNTR), noradrenergic (SLC6A2, rs36021), and GABAergic (GABRA2, rs279858; GABRA6, rs3811995) genes were examined given prior support for associations with temperament, externalizing behavior, and substance use problems.