Genetic and environmental influences on the co-morbidity between depression, panic disorder, agoraphobia, and social phobia: a twin study

Abstract

Background: Major depression (MD) and anxiety disorders such as panic disorder (PD), agoraphobia (AG), and social phobia (SP) are heritable and highly co-morbid. However, the relative importance of genetic and environmental etiology of the covariation between these disorders, particularly the relationship between PD and AG, is less clear.

Methods: This study measured MD, PD, and AG in a population sample of 5,440 twin pairs and 1,245 single twins, about 45% of whom were also scored for SP. Prevalences, within individual co-morbidity and twin odds ratios for co-morbidity, are reported. A behavioral genetic analysis of the four disorders using the classical twin design was conducted.

Results: Odds ratios for MD, PD, AG, and SP in twins of individuals diagnosed with one of the four disorders were increased. Heritability estimates under a threshold-liability model for MD, PD, AG, and SP respectively were .33 (CI: 0.30-0.42), .38 (CI: 0.24-0.55), .48 (CI: 0.37-0.65), and .39 (CI: 0.16-0.65), with no evidence for any variance explained by the common environment shared by twins. We find that a common genetic factor explains a moderate proportion of variance in these four disorders. The genetic correlation between PD and AG was .83.

Conclusion: MD, PD, AG, and SP strongly co-aggregate within families and common genetic factors explain a moderate proportion of variance in these four disorders. The high genetic correlation between PD and AG and the increased odds ratio for PD and AG in siblings of those with AG without PD suggests a common genetic etiology for PD and AG.

Figure 1

Full multivariate model in which a Cholesky decomposition is applied to the genetic and environmental variance-covariance matrices with standardized path coefficients showing the relationship between Depression (MD), Panic (PD), Agoraphobia (AG), and Social Phobia (SP). Path coefficients can be squared to get the percentage of variance accounted for. The Cholesky factors have been decomposed into additive genetic (A), shared (C) and non-shared environmental (E) influences. The most parsimonious model is shown with solid lines and path estimates in bold.