Posttraumatic stress disorder and the genetic structure of comorbidity

Abstract

This study used structural equation modeling to examine the genetic and environmental architecture of latent dimensions of internalizing and externalizing psychiatric comorbidity and explored structural associations between posttraumatic stress disorder (PTSD) and these dimensions. Data were drawn from the Vietnam Era Twin Registry and included lifetime diagnoses for PTSD and a range of other psychiatric disorders for 3,372 male-male twin pairs. Examination of the phenotypic structure of these disorders revealed that PTSD cross-loaded on both Internalizing and Externalizing common factors. Biometric analyses suggested largely distinct genetic risk factors for the latent internalizing and externalizing comorbidity dimensions, with the total heritability of the Externalizing factor (69%) estimated to be significantly stronger than that for Internalizing (41%). Nonshared environment explained the majority of the remaining variance in the Internalizing (58%) and Externalizing (20%) factors. Shared genetic variance across the 2 dimensions explained 67% of their phenotypic correlation (r = .52). These findings have implications for conceptualizations of the etiology of PTSD and its location in an empirically based nosology.

Figure 1

Common pathway model testing sequence. The figure shows the model testing sequence for one twin. Identical models were simultaneously evaluated in the second twin from each pair but are not depicted in the figure for the sake of presentation clarity. Common factors are denoted by circles and observed indicators by squares. The first common pathway model (the simple ACE model) included the paths depicted by solid black lines (Paths a1–e1 and a2–e2). The c1 pathway was set to zero in all models. The second common pathway model (the Cholesky-A model) added the path denoted by the long-dotted line (Path a1-b) and the third common pathway model (the Cholesky-AE model) added in the path denoted by the short-dotted gray line (Path e1-b). A = additive genetic; C = common environment; E = nonshared environment; INT = internalizing; EXT = externalizing; MDD = major depressive disorder; Dys = dysthymia; GAD = generalized anxiety disorder; PD = panic disorder; PTSD = posttraumatic stress disorder; ASPD = antisocial personality disorder; Drug = drug abuse/dependence; Alch = alcohol abuse/dependence.

Figure 2

Standardized results from best-fitting biometric model. All values are completely standardized parameter estimates. All paths are statistically significant at the p < .001 level with the following exceptions: All paths fixed or estimated to be 0 or .01 were not significant, the residual genetic paths to PTSD and alcohol abuse/dependence were not significant, the residual common environment path to PTSD was significant at the p = .006 level, and the residual genetic path to ASPD was significant at the p = .03 level. A = additive genetic; C = common environment; E = nonshared environment; INT = internalizing; EXT = externalizing; MDD = major depressive disorder; Dys = dysthymia; GAD = generalized anxiety disorder; PD = panic disorder; PTSD = posttraumatic stress disorder; ASPD = antisocial personality disorder; Drug = drug abuse/dependence; Alch = alcohol abuse/dependence.