A twin study of gene-environment interaction in generalized anxiety disorder

Genetic liability and Stressful Life Events (SLEs) are both recognized risk factors for the onset of Generalized Anxiety Disorder (GAD), however we know little about how they interact. We applied discrete time survival analysis to a population-based sample of female-female twins (590 monozygotic and 440 dizygotic pairs) assessed on two occasions by person interview that assessed for SLEs and the onset of GAD in the preceding year. Four of the "personal" SLEs and two of the aggregate "network" SLEs predicted the onset of GAD (4-week definition) in the month of occurrence with odds ratio (OR) ranging from 2.3 to 4.6. The impact of genetic liability on the risk for GAD was also significant. The best fitting model for the joint effect of SLEs and the genetic liability on onset of GAD suggested genetic control of the sensitivity to the anxiogenic effects of the SLEs. A linear regression analysis indicated significant genotype x environment interaction in the prediction of episode onset of GAD by severe SLEs. There were however differences in the pattern of the type of SLEs that were predictive of GAD and Major Depression in the same sample, loss events in particular being more depressogenic than anxiogenic.