G×E crossover of risk has been observed in longitudinal studies [24, 82, 83, 85]. For example, in the ALSPAC study, girls with the low-activity MAOA-LPR variant showed both increased hyperactivity after stress exposure and decreased hyperactivity after little or no stress exposure compared with girls without the low-activity variant [24]. Another example comes from the Mannheim Children’s Study in which adolescents were genotyped for the functional COMT Val158-Met polymorphism. In Met/Met homozygotes only, low perceived parental supervision at age 15 was associated with increased drinking activity at age 19, but favorable parental supervision was associated with lower drinking activity compared with the other two genotype groups [93]. Thus, one genotype might confer both risk of behavioral disinhibition in the presence of stress and behavioral inhibition in the absence of stress. Genetic background may therefore make some individuals more susceptible to good and bad environmental influences—the so-called differential susceptibility hypothesis [94]. However, it should be noted that some have questioned whether the crossover effect might actually be a statistical artifact [92].
