Erika J. Wolf

Posttraumatic Stress Disorder and the Genetic Structure of Comorbidity

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.

Personality-based latent classes of posttraumatic psychopathology: personality disorders and the internalizing/externalizing model.

Prior research using the Brief Form of the Multidimensional Personality Questionnaire (MPQ-BF; Patrick, Curtin, & Tellegen, 2002) has shown evidence of 3 temperament-based subtypes--termed internalizing, externalizing, and simple PTSD--among individuals with symptoms of posttraumatic stress disorder (PTSD; Miller, Greif, & Smith, 2003). This study sought to replicate and extend research in this area by conducting a latent profile analysis of higher order temperament scales from the MPQ-BF using a new sample of 208 veterans with symptoms of PTSD. Results suggest that a 3-class solution reflecting internalizing, externalizing, and simple subtypes of posttraumatic psychopathology provided the best fit to the data. The externalizing subtype was characterized by features of antisocial, borderline, histrionic, and narcissistic personality disorders on the International Personality Disorder Examination (Loranger, 1999) as well as low levels of constraint and high levels of negative emotionality on the MPQ-BF. In contrast, individuals in the internalizing class exhibited features of schizoid and avoidant personality disorders, low levels of positive emotionality, and high levels of negative emotionality. The simple subtype was defined by low levels of comorbid personality disorder features and relatively normal personality profiles. Findings support the reliability of this typology and support the relevance of the internalizing and externalizing model to the structure of personality disorders.

The MMPI-2 Restructured Clinical Scales in the Assessment of Posttraumatic Stress Disorder and Comorbid Disorders

This study examined the psychometric properties of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) Restructured Clinical Scales (RCSs) in individuals with posttraumatic stress disorder (PTSD) receiving clinical services at Department of Veterans Affairs medical centers. Study 1 included 1,098 men who completed the MMPI-2 and were assessed for a range of psychological disorders via structured clinical interview. Study 2 included 136 women who completed the MMPI-2 and were interviewed with the Clinician Administered Scale for PTSD. The utility of the RCSs was compared with that of the Clinical Scales (CSs) and the Keane PTSD (PK) scale. The RCSs demonstrated good psychometric properties and patterns of associations with other measures of psychopathology that corresponded to current theory regarding the structure of comorbidity. A notable advantage of the RCSs compared with the MMPI-2 CSs was their enhanced construct validity and clinical utility in the assessment of comorbid internalizing and externalizing psychopathology. The PK scale demonstrated incremental validity in the prediction of PTSD beyond that of the RCSs or CSs.

Longitudinal associations between post-traumatic stress disorder and metabolic syndrome severity.

BACKGROUNDnPost-traumatic stress disorder (PTSD) is associated with elevated risk for metabolic syndrome (MetS). However, the direction of this association is not yet established, as most prior studies employed cross-sectional designs. The primary goal of this study was to evaluate bidirectional associations between PTSD and MetS using a longitudinal design.nnnMETHODnA total of 1355 male and female veterans of the conflicts in Iraq and Afghanistan underwent PTSD diagnostic assessments and their biometric profiles pertaining to MetS were extracted from the electronic medical record at two time points (spanning ~2.5 years, n = 971 at time 2).nnnRESULTSnThe prevalence of MetS among veterans with PTSD was just under 40% at both time points and was significantly greater than that for veterans without PTSD; the prevalence of MetS among those with PTSD was also elevated relative to age-matched population estimates. Cross-lagged panel models revealed that PTSD severity predicted subsequent increases in MetS severity (β = 0.08, p = 0.002), after controlling for initial MetS severity, but MetS did not predict later PTSD symptoms. Logistic regression results suggested that for every 10 PTSD symptoms endorsed at time 1, the odds of a subsequent MetS diagnosis increased by 56%.nnnCONCLUSIONSnResults highlight the substantial cardiometabolic concerns of young veterans with PTSD and raise the possibility that PTSD may predispose individuals to accelerated aging, in part, manifested clinically as MetS. This demonstrates the need to identify those with PTSD at greatest risk for MetS and to develop interventions that improve both conditions.

Avoidant Coping as a Predictor of Mortality in Veterans With End-Stage Renal Disease

OBJECTIVEnThe aim of this study was to examine the role of active and avoidant coping strategies in predicting mortality in 61 veterans with end-stage renal disease.nnnDESIGNnParticipants completed a self-report measure of coping strategies (The COPE; Carver, Scheier, & Weintraub, 1989) and were interviewed as part of a structured assessment to determine their appropriateness for renal transplant. On average, participants were then followed for 9 years via medical record review to determine mortality status.nnnMAIN OUTCOME MEASURESnMortality, as predicted by factor scores on active and avoidant coping factors estimated via confirmatory factor analysis of select COPE subscales.nnnRESULTSnA Cox regression revealed that a unit change in avoidant coping was associated with a 114% increase in odds of mortality, even after controlling for variance attributable to demographic variables. There was also a statistical trend indicating that this association might be mediated by poor attendance at medical appointments. Active coping did not predict mortality.nnnCONCLUSIONnResults demonstrate the importance of assessing coping style in this population; clinical implications of these findings and possible mechanisms of this effect are discussed.

Comparison of Treatment for Post-Traumatic Stress Disorder among Three Department of Veterans Affairs Medical Centers

The objective of the present study was to compare three specialized treatment programs for post-traumatic stress disorder (PTSD) in different Veterans Affairs medical centers, in terms of the format of therapeutic services and the medications prescribed for PTSD. Chart review methods were used to examine medical records for 50 patients from each facility over a 6-month period. Results indicated that the medications prescribed were fairly consistent across sites, although they were not always consistent with treatment recommendations. Therapy formats for two of the facilities were quite different, with one offering more case management services and the other offering more intensive individual and group therapy services. Additional research is needed to broaden our knowledge of how PTSD is being treated currently and to study the effectiveness of the treatment strategies being used.

Network models of DSM–5 posttraumatic stress disorder: Implications for ICD–11.

Recent proposals for revisions to the 11th edition of the International Classification of Diseases (ICD–11) posttraumatic stress disorder (PTSD) diagnostic criteria have argued that the current symptom constellation under the Diagnostic and Statistical Manual of Mental Disorders-5 is unwieldy and includes many symptoms that overlap with other disorders. The newly proposed criteria for the ICD–11 include only 6 symptoms. However, restricting the symptoms to those included in the ICD–11 has implications for PTSD diagnosis prevalence estimates, and it remains unclear whether these 6 symptoms are most strongly associated with a diagnosis of PTSD. Network analytic methods, which assume that psychiatric disorders are networks of interrelated symptoms, provide information regarding which symptoms are most central to a network. We estimated network models of PTSD in a national sample of veterans of the Iraq and Afghanistan wars. In the full sample, the most central symptoms were persistent negative emotional state, efforts to avoid external reminders, efforts to avoid thoughts or memories, inability to experience positive emotions, distressing dreams, and intrusive distressing thoughts or memories; that is, 3 of the 6 most central items to the network would be eliminated from the diagnosis under the current proposal for ICD–11. An empirically defined index summarizing the most central symptoms in the network performed comparably to an index reflecting the proposed ICD–11 PTSD criteria at identifying individuals with an independently assessed DSM–5 defined PTSD diagnosis. Our results highlight the symptoms most central to PTSD in this sample, which may inform future diagnostic systems and treatment.

Combat exposure severity as a moderator of genetic and environmental liability to post-traumatic stress disorder.

BACKGROUNDnTwin studies of veterans and adults suggest that approximately 30-46% of the variance in post-traumatic stress disorder (PTSD) is attributable to genetic factors. The remaining variance is attributable to the non-shared environment, which, by definition, includes combat exposure. This study used a gene by measured environment twin design to determine whether the effects of genetic and environmental factors that contribute to the etiology of PTSD are dependent on the level of combat exposure.nnnMETHODnThe sample was drawn from the Vietnam Era Twin Registry (VETR) and included 620 male-male twin pairs who served in the US Military in South East Asia during the Vietnam War era. Analyses were based on data from a clinical diagnostic interview of lifetime PTSD symptoms and a self-report measure of combat exposure.nnnRESULTSnBiometric modeling revealed that the effects of genetic and non-shared environment factors on PTSD varied as a function of level of combat exposure such that the association between these factors and PTSD was stronger at higher levels of combat exposure.nnnCONCLUSIONSnCombat exposure may act as a catalyst that augments the impact of hereditary and environmental contributions to PTSD. Individuals with the greatest exposure to combat trauma were at increased risk for PTSD as a function of both genetic and environmental factors. Additional work is needed to determine the biological and environmental mechanisms driving these associations.

The Structure of Personality Disorders in Individuals with Posttraumatic Stress Disorder

Research on the structure of personality disorders (PDs) has relied primarily on exploratory analyses to evaluate trait-based models of the factors underlying the covariation of these disorders. This study used confirmatory factor analysis to evaluate whether a model that included both PD traits and a general personality dysfunction factor would account for the comorbidity of the PDs better than a trait-only model. It also examined if the internalizing/externalizing model of psychopathology, developed previously through research on the structure of Axis I disorders, might similarly account for the covariation of the Axis II disorders in a sample of 245 veterans and nonveterans with posttraumatic stress disorder. Results indicated that the best fitting model was a modified bifactor structure composed of nine lower-order common factors. These factors indexed pathology ranging from aggression to dependency, with the correlations among them accounted for by higher-order Internalizing and Externalizing factors. Further, a general factor, reflecting a construct that we termed boundary disturbance, accounted for additional variance and covariance across nearly all the indicators. The Internalizing, Externalizing, and Boundary Disturbance factors evidenced differential associations with trauma-related covariates. These findings suggest continuity in the underlying structure of psychopathology across DSM-IV Axes I and II and provide empirical evidence of a pervasive, core disturbance in the boundary between self and other across the PDs.

Low Basal Cortisol and Startle Responding as Possible Biomarkers of PTSD: The Influence of Internalizing and Externalizing Comorbidity

Comorbidity presents significant problems to investigators engaged in the search for biomarkers of post-traumatic stress disorder (PTSD) because it means that multiple overlapping psychiatric phenotypes may be present in any PTSD sample. This chapter reviews research on an internalizing/externalizing model of post-traumatic psychopathology and discusses its relevance to the search for PTSD biomarkers. It focuses on two candidate biomarkers that have been studied extensively in relation to PTSD—basal cortisol level and startle reflex amplitude—but have yielded complicated and mixed results. Our review of the cortisol literature finds evidence for links between disorders of the internalizing spectrum and elevated levels of cortisol and links between externalizing psychopathology and low levels of cortisol. The review of the startle reflex literature reveals an association between exaggerated startle and fear-related disorders of the internalizing spectrum. These findings illustrate how individual differences in internalizing and externalizing comorbidity may moderate associations between these measures and PTSD diagnostic status. The chapter concludes with a discussion of the advantages of studying latent dimensions of comorbidity in future PTSD biomarker research.