Generalized anxiety disorder (GAD), panic disorder (PD) and post-traumatic stress disorder (PTSD) often co-occur. We investigated whether and to what degree genetic and environmental contributions overlap among symptoms of GAD, symptoms of PD and PTSD. Subjects were 3327 monozygotic and dizygotic male–male twin pair members of the Vietnam Era Twin Registry who participated in a 1992 telephone administration of the Diagnostic Interview Schedule Version 3 Revised (DIS3R). Genetic model fitting was performed to estimate the magnitude of genetic and environmental contributions to the lifetime co-occurrence of GAD symptoms, PD symptoms and PTSD. The liability for GAD symptoms was due to a 37.9% additive genetic contribution common to PD symptoms and PTSD. Liability for PD symptoms was due to a 20.7% additive genetic contribution common to GAD symptoms and PTSD, and a 20.1% additive genetic influence specific to PD symptoms. Additive genetic influences common to symptoms of GAD and PD accounted for 21.3% of the genetic variance in PTSD. Additive genetic influences specific to PTSD accounted for 13.6% of the genetic variance in PTSD. Remaining variance for all three disorders was due to unique environmental factors both common and specific to each phenotype. These results suggest that these disorders each have etiologically distinct components and also have significant genetic and unique environmental contributions in common.
Generalized anxiety disorder (GAD), panic disorder (PD) and post-traumatic stress disorder (PTSD) are all classified as anxiety disorders in the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R) (American Psychiatric Association, 1987). The characteristic features of these three anxiety disorders are symptoms of anxiety and avoidance behavior. In GAD and PD, anxiety is usually the predominant symptom. GAD is characterized by excessive and persistent anxiety and worry, while PD is characterized by spontaneous and sudden onset of a discrete period of intense apprehension, terror and discomfort. PTSD is unique among anxiety disorders because its diagnosis requires exposure to a traumatic event outside the range of usual human experience. It is characterized by re-experiencing the traumatic event, accompanied by symptoms of increased arousal and by avoidance of stimuli associated with the trauma.
GAD and PD often co-occur with PTSD. Helzer et al. (1987) in the Epidemiologic Catchment Area study of psychiatric disorders in the general population, Breslau et al. (1991) in a study of traumatic events and post-traumatic stress disorder in an urban population of young adults, and Kessler et al. (1995) in the National Comorbidity Survey all found an increase in risk of GAD and PD among men and women with PTSD.
Evidence to date suggests that liability to GAD (Andrews et al., 1990, Kendler et al., 1992 and Skre et al., 1993), PD (Crowe et al., 1983, Crowe, 1985, Martin et al., 1988, Skre et al., 1993, Torgersen, 1983, Weissman, 1993 and Kendler et al., 1995) and PTSD (Davidson et al., 1985, Davidson et al., 1989, Skre et al., 1993, True et al., 1993, Comings et al., 1996 and Reich et al., 1996) has a genetic component. Scherrer et al. (2000) in a previous study of Vietnam Era Twin (VET) Registry twins found that the risk for symptoms of GAD and symptoms of PD is partly due to a common genetic influence. PTSD has been found to be more prevalent among co-twins of probands with anxiety disorders, suggesting potential for a common genetic influence (Skre et al., 1993), but the degree to which genetic and shared environmental contributions to GAD symptoms and PD symptoms are common to vulnerability for PTSD is not known. Understanding the degree to which genetic and shared environmental factors influence these phenotypes may help explain the greater than chance lifetime co-occurrence of GAD, PD and PTSD.
We analyzed telephone interview data collected from members of the Vietnam Era Twin (VET) Registry in a multivariate genetic model to estimate the genetic and environmental factors which influence the lifetime co-occurrence of GAD symptoms, PD symptoms and PTSD. In addition, the magnitudes of common and disorder-specific genetic and environmental factors were estimated. Because DSM-IV diagnoses were not available at the time of data collection, our present analyses use DSM-III-R criteria.
In this sample of VET Registry twins, the risk for lifetime co-occurrence of GAD symptoms, PD symptoms and PTSD were best explained by models which allowed for additive genetic influences common to all three phenotypes. In addition, PD symptoms and PTSD were influenced by disorder-specific additive genetic factors. Each disorder was influenced by common and unique environmental factors.
Under the best fitting model for lifetime co-occurrence of GAD symptoms, PD symptoms and PTSD, the variances in liability for GAD symptoms (37.9%, common additive genetic contribution only), PD symptoms (40.8%, combining 20.7% in common to GAD symptoms and PTSD, and 20.1% specific to PD symptoms) and PTSD (34.9%, combining 21.3% in common to GAD symptoms and PD symptoms, and 13.6% specific to PTSD) were accounted for by genetic contributions. That is, PD symptoms and PTSD partly shared additive genetic influences with GAD symptoms and had disorder-specific additive genetic contributions, which were not shared with the genetic vulnerability of GAD symptoms.
This finding of a genetic influence is consistent with previous univariate model-fitting results for GAD symptoms and PD symptoms in VET Registry members which found that additive genetic factors accounted for 37.2 and 43.4% of the risk of these disorders, respectively (Scherrer et al., 2000). This is also consistent with an analysis of DSM-III-R based diagnoses in which the concordance for GAD among MZ twins was 4.3 times greater than for DZ twins, suggesting a genetic influence (Skre et al., 1993). In addition, our results are consistent with a multivariate genetic analysis of phobia, GAD, PD, bulimia, major depression and alcoholism (Kendler et al., 1995) which found 12% of the genetic variance in PD overlapped with GAD and 32% of the variance in PD did not overlap with GAD in female twins.
