Determining sample size requirements for structural equation modeling (SEM) is a challenge often faced by investigators, peer reviewers, and grant writers. Recent years have seen a large increase in SEMs in the behavioral science literature, but consideration of sample size requirements for applied SEMs often relies on outdated rules-of-thumb. This study used Monte Carlo data simulation techniques to evaluate sample size requirements for common applied SEMs. Across a series of simulations, we systematically varied key model properties, including number of indicators and factors, magnitude of factor loadings and path coefficients, and amount of missing data. We investigated how changes in these parameters affected sample size requirements with respect to statistical power, bias in the parameter estimates, and overall solution propriety. Results revealed a range of sample size requirements (i.e., from 30 to 460 cases), meaningful patterns of association between parameters and sample size, and highlight the limitations of commonly cited rules-of-thumb. The broad “lessons learned” for determining SEM sample size requirements are discussed.
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.
BACKGROUND Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = −0.17, p = .00054), and smaller amygdalae (d = −0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma.
Context The nature of the relationship of dissociation to posttraumatic stress disorder (PTSD) is controversial and of considerable clinical and nosological importance. Objective To examine evidence for a distinct subtype of PTSD characterized by high levels of dissociation. Design A latent profile analysis of cross-sectional data from structured clinical interviews indexing DSM-IV symptoms of current PTSD and dissociation. Setting VA Boston and New Mexico VA Healthcare Systems. Participants 492 Veterans and their intimate partners, all of whom had histories of trauma. Participants reported exposure to a variety of traumatic events including combat, childhood physical and sexual abuse, partner abuse, motor vehicle accidents, and natural disasters, with most participants reporting exposure to multiple types of traumatic events. Forty-two percent of the sample met criteria for a current diagnosis of PTSD. Main Outcome Measures Item-level scores on the Clinician Administered PTSD Scale. Results A latent profile analysis suggested a three class solution: a low severity subgroup, a high PTSD severity subgroup characterized by elevations across the 17 core symptoms of the disorder, and a small but distinctly dissociative subgroup that comprised 12% of individuals with a current diagnosis of PTSD. The latter group was characterized by severe PTSD symptoms combined with marked elevations on items assessing flashbacks, derealization, and depersonalization. Individuals in this subgroup also endorsed greater exposure to childhood and adult sexual trauma compared to the other two groups suggesting a possible etiologic link with the experience of repeated sexual trauma. Conclusions Results support the subtype hypothesis of the association between PTSD and dissociation and suggest that dissociation is a highly salient facet of posttraumatic psychopathology in a subset of individuals with the disorder.
We describe the results of the first genome-wide association study of PTSD performed using trauma-exposed white non-Hispanic participants from a cohort of veterans and their intimate partners (295 cases and 196 controls). Several SNPs yielded evidence of association. One SNP (rs8042149), located in the retinoid-related orphan receptor alpha gene (RORA), reached genome-wide significance. Nominally significant associations were observed for other RORA SNPs in two African American replication samples—one from the veteran cohort (43 cases and 41 controls) and another independent cohort (100 cases and 421 controls). However, only the associated SNP from the veteran African American replication sample survived gene-level multiple testing correction. RORA has been implicated in prior GWAS studies of psychiatric disorders and is known to play an important role in neuroprotection and other behaviorally-relevant processes. This study represents an important step towards identifying the genetic underpinnings of PTSD.
The Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) is currently undergoing revisions in advance of the next edition, DSM-5. The DSM-5 posttraumatic stress disorder workgroup has proposed numerous changes to the PTSD diagnosis. These include the addition of new symptoms, revision of existing ones, and a new four-cluster organization (Friedman, Resick, Bryant, & Brewin, 2011). We conducted two Internet-based surveys to provide preliminary information about how proposed changes might impact PTSD prevalence and clarify the latent structure of the new symptom set. We used a newly developed instrument to assess event exposure and lifetime and current DSM-5 PTSD symptoms among a nationally representative sample of American adults (N = 2,953) and a clinical convenience sample of U.S. military veterans (N = 345). Results from both samples indicated that the originally proposed DSM-5 symptom criteria (i.e., requiring 1 B, 1 C, 3 D, and 3 E symptoms) yielded considerably lower PTSD prevalence estimates compared with DSM-IV estimates. These estimates were more comparable when the DSM-V D and E criteria were relaxed to 2 symptoms each (i.e., the revised proposal). Confirmatory factor analyses (CFA) indicated that the factor structure implied by the four-symptom criteria provided adequate fit to the data in both samples, and a DSM-5 version of a dysphoria model (Simms, Watson, & Doebbeling, 2002) yielded modest improvement in fit. Item-response theory and CFA analyses indicated that the psychogenic amnesia and new reckless/self-destructive behavior symptom deviated from the others in their respective symptom clusters. Impli cations for final formulations of DSM-5 PTSD criteria are discussed.
Results provide support for a dissociative subtype of PTSD and also suggest that dissociation may play a role in the frequent co-occurrence of PTSD and borderline PD among women. These results are pertinent to the on-going revisions to the DSM and suggest that consideration should be given to incorporating a dissociative subtype into the revised PTSD criteria.
Complex posttraumatic stress disorder (CPTSD) has been proposed as a diagnosis for capturing the diverse clusters of symptoms observed in survivors of prolonged trauma that are outside the current definition of PTSD. Introducing a new diagnosis requires a high standard of evidence, including a clear definition of the disorder, reliable and valid assessment measures, support for convergent and discriminant validity, and incremental validity with respect to implications for treatment planning and outcome. In this article, the extant literature on CPTSD is reviewed within the framework of construct validity to evaluate the proposed diagnosis on these criteria. Although the efforts in support of CPTSD have brought much needed attention to limitations in the trauma literature, we conclude that available evidence does not support a new diagnostic category at this time. Some directions for future research are suggested.
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