Genetic and environmental influences modulating risk of SUDs change developmentally and across the lifespan. In a longitudinal twin study, Kendler and colleagues21 found that gene effects in alcohol, cannabis, and nicotine addictions were low in early adolescence but their relative importance gradually grew in adulthood. In contrast, the effect of family environment declined from childhood to adulthood. A possible explanation is that as they mature, people have increasing latitude to shape their choices and social environments, thus increasing the relative importance of genotype.22 Another explanation is that some genetic factors are important only after repetitive exposure to addictive agents. Also, some alleles may only alter responses of the adult brain. Genetic variation within the CHRNA5–CHRNA3–CHRNB4 gene cluster appears to have a stronger effect on smoking behavior in adulthood than in adolescence and moderated the risk of developing a severe pattern of smoking in subjects who had already initiated nicotine use.19 In contrast, the TTC12–ANKK1–DRD2 and MAOA appears to influence personality characteristics such as novelty seeking and impulsivity that promote substance initiation.19
