The longstanding recognition that both genes (“nature”) and environments (“nurture”) contribute to the etiology of depression has motivated a great deal of interest in studying GxE. GxE studies examine the degree to which genetic variants modify the association between environmental factors and depression (or similarly, the extent to which environmental factors modify the association between genes and depression).70-72 Typically, GxE studies have assumed a “diathesis-stress” model, where a genetic liability, also referred to as a diathesis, interacts with a stressful life event to give rise to depression. In this model, genes either exacerbate or buffer the effects of stress.73 More recently, however, the concept of GxE has been expanded to incorporate more positive aspects of the environment, such as social support, psychosocial interventions, and other protective factors that reduce risk for disease.74,75 Here, emerging work has focused on differential susceptibility to the environment,76,77 or the extent to which genetic variation makes individuals more likely to respond adversely to negative environments, but more positively to salutary environments.
