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Depression and Gender Differences 301“two-hit” model of the rise in depression during adolescence because both vulnerabilityto stress and stress itself are increasing.Integrating the Cognitive Vulnerability-Stressand Genetic Vulnerability-Stress ModelsTo date, the cognitive and genetic approaches to depression have proceeded inparallel with little “cross-talk.” Given the major success of each, it is time to integratethem. Providing a foundation for such an integration, two independent studieshave shown that cognitive vulnerability has a genetic component (Lau, Rijsdijk,& Eley, in press; Schulman, Keith, & Seligman, 1993). In particular, higher concordancesfor cognitive vulnerability among monozygotic than dizygotic twinshave been reported (Schulman et al., 1993). Similarly, in a study of over 1,300adolescent twin and sibling pairs, model-fitting techniques revealed a genetic influenceon cognitive vulnerability (attributional style; Lau et al., in press). For anumber of reasons, it is highly plausible that the 5-HTTLPR genotype, in particular,is related to cognitive vulnerability. At a general level, cognitive vulnerabilityand 5-HTTLPR genotype vulnerability share some critical similarities. Bothappear related to ethnicity, with African Americans less vulnerable than Caucasians.Moreover, both participate in vulnerability-stress interactions that moderatethe effects of stress on the development of depression. At a more specific level,exciting recent work (Meyer et al., 2003, 2004) suggests that serotonin modulatesdysfunctional attitudes, one type of cognitive vulnerability for depression. Finally,a link has been found between the 5-HTTLPR genotype and negative emotionality/neuroticism(e.g., Lesch et al., 1996, but for an exception, see Gelertner et al.,1998), which, in turn, interacts with negative life events to predict the developmentof cognitive vulnerability among children making the transition to adolescence(Mezulis, Hyde, & Abramson, in press).Thus, a growing body of work suggests a link between cognitive vulnerabilityand the 5-HTTLPR genotype. Building on these findings, it will be important todetermine whether cognitive vulnerability is related to the 5-HTTLPR genotypeand whether cognitive vulnerability mediates, at least in part, the effects of thisgenotype on depression in response to the rise in adolescent stressors. The time isripe to test such an integrated cognitive/genetic vulnerability-stress model as anexplanation for the adolescent surge and emergence of gender differences in depressionin a prospective study of children making the transition to adolescence.Implications for PreventionInsofar as depression has been ranked as the “single most burdensome disease”(Murray & Lopez, 1996) due to its unique combination of high lifetime prevalence,early age of onset, high chronicity, and great role impairment (Kessler, 2000), it