These findings are in line with the differential-susceptibility hypothesis proposed by Belsky et al. (2009). According to this hypothesis, the same individuals who are most adversely affected by negative environments are also those who are most likely to benefit from positive environments. Belsky et al. referred to genetic factors that operate in this way as “plasticity genes,” and contrasted this framework for conceptualizing gene-environment interaction with the diathesis-stress framework, which focuses on “vulnerability genes” and has been the predominant model in psychiatric genetics. Under the diathesis-stress framework, gene-environment interaction is generally conceptualized as certain individuals being more susceptible to psychiatric problems in the context of adverse environmental conditions than other individuals are. A diathesis-stress framework hypothesizes a fan-shaped interaction (as illustrated in Fig. 4a), whereby there is a stronger association between genotype and outcome under adverse environmental conditions than under benign environmental conditions. In contrast, the differential-susceptibility hypothesis predicts a crossover interaction (Fig. 4b), whereby the association between genotype and outcome is actually reversed at environmental extremes, such that the individuals at highest risk under adverse environmental conditions are at lowest risk under positive environmental conditions.
