Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders.

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK ). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Feasibility of Virtual Reality Exposure Therapy in the Treatment of Danish Veterans with Post-Traumatic Stress Disorder: A Mixed Method Pilot Study.

The BraveMind virtual reality exposure therapy (VRET) has been developed and has shown efficacy for U.S. service members and veterans. As the first study to date, the present study examined the feasibility of BraveMind VRET for non-U.S. military veterans. Moreover, the study sought to explore in-depth the participants' experiences with BraveMind VRET. Nine Danish veterans with post-traumatic stress disorder (PTSD) after deployment to Afghanistan participated in the study. PTSD, depression, and quality of life were assessed at pretreatment, post-treatment, and 3-month followup. The treatment consisted of 10 BraveMind VRET sessions. Semistructured interviews with treatment completers were conducted post-treatment to ascertain views about the treatment, in general, and the BraveMind VR system in particular. Thematic qualitative analysis was conducted at the semantic level using an inductive approach. There were significant reductions in pre- to post-treatment self-reported PTSD and significant improvements in quality of life. Treatment gains were maintained at 3-month followup. Pre- to post-treatment Cohen's d effect sizes were large for self-reported PTSD (PTSD Checklist-Civilian Version [PCL-C]: d = 1.55). Qualitative results indicated that the virtual environment of the BraveMind VR system does not entirely map the reality of Danish soldiers in Afghanistan. However, this was not experienced as a hindering factor in therapy. Findings indicate that BraveMind VRET is an acceptable, safe, and effective treatment for Danish veterans with PTSD. The qualitative results emphasize the importance of a strong therapeutic alliance, as VRET is experienced as more emotional straining than regular trauma-focused therapy.

Early prediction of mental health problems following military deployment: Integrating pre- and post-deployment factors in neural network models.

Military personnel deployed to war zones are at increased risk of mental health problems such as posttraumatic stress disorder (PTSD) or depression. Early pre- or post-deployment identification of those at highest risk of such problems is crucial to target intervention to those in need. However, sufficiently accurate models predicting objectively assessed mental health outcomes have not been put forward. In a sample consisting of all Danish military personnel who deployed to war zones for the first (N = 27,594), second (N = 11,083) and third (N = 5,161) time between 1992 and 2013, we apply neural networks to predict psychiatric diagnoses or use of psychotropic medicine in the years following deployment. Models are based on pre-deployment registry data alone or on pre-deployment registry data in combination with post-deployment questionnaire data on deployment experiences or early post-deployment reactions. Further, we identified the most central predictors of importance for the first, second, and third deployment. Models based on pre-deployment registry data alone had lower accuracy (AUCs ranging from 0.61 (third deployment) to 0.67 (first deployment)) than models including pre- and post-deployment data (AUCs ranging from 0.70 (third deployment) to 0.74 (first deployment)). Age at deployment, deployment year and previous physical trauma were important across deployments. Post-deployment predictors varied across deployments but included deployment exposures as well as early post-deployment symptoms. The results suggest that neural network models combining pre- and early post-deployment data can be utilized for screening tools that identify individuals at risk of severe mental health problems in the years following military deployment.

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information.

BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. RESULTS: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. CONCLUSIONS: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

Forecasting military mental health in a complete sample of Danish military personnel deployed between 1992-2013.

OBJECTIVE: Mental health problems (MHP) are a relatively common consequence of deployment to war zones. Early identification of those at risk of post-deployment MHP would improve prevention efforts. However, screening instruments based on linear models have not been successful. Machine learning (ML) has shown promise for providing the methodological frame for better prognostic models. METHODS: The study population was all Danish military personnel deployed for the first time between January 1, 1992 and December 31, 2013. From extensive registry data, 21 pre- or at-deployment predictors comprising early adversity, social, clinical and demographic variables were used to predict psychiatric contacts (psychiatric diagnosis and/or use of psychotropic medicine) occurring within 6.5 years after homecoming. Four supervised ML methods (penalized logistic regression, random forests, support vector machines and gradient boosting machines) were compared in ability to classify those with high risk of post-deployment MHP and those without. RESULTS: Of 27594 subjects, 2175 (8%) had a psychiatric contact. All four ML methods applied had performances well above chance (Area under the Receiver-operating Curve 0.62-0.68). Positive predictive value for the best model was 0.16. A range of pre-deployment factors were found to be predictive of post-deployment psychiatric contacts. CONCLUSIONS: ML methods can be useful in early identification of soldiers with high risk of MPH in the years following their first deployment. However, performances were modest and positive predictive values were low, limiting the applicability of the models for pre-deployment screening. Future studies should include neurobiological data and deployment experiences to increase accuracy of the models.

Trajectories of depression symptoms from pre- to post- deployment: Does previous trauma predict symptom increase?

BACKGROUND: A significant minority of individuals experience depression following military deployment. The course of depression symptoms varies over time and across individuals; several factors including combat exposure influence depressions incidence and course. Importantly, previous trauma, especially in childhood, have been found increase the risk of post-deployment depression. METHODS: In a prospective sample of 530 soldiers deployed to Afghanistan in 2009, we used latent growth mixture modeling (LGMM) to estimate trajectories of depression symptoms from before through 6.5 years after deployment. In a multinomial logistic regression model, we tested if childhood and adult life trauma predicted trajectory membership in combination with combat exposure and neuroticism. RESULTS: We identified a large trajectory of few depression symptoms from before through 6.5 years after deployment (Low-stable, 86.5%), a trajectory with somewhat elevated symptoms (Medium-fluctuating, 4.0%), and a trajectory with few symptoms before deployment and a steep increase to a severe symptom level 6.5 years after deployment (Low-increasing, 9.4%). The Low-increasing trajectory was predicted by lower rank and childhood trauma, while the Medium-fluctuating trajectory was predicted by neuroticism, adult life trauma, and post-deployment PTSD symptoms. LIMITATIONS: Attrition and use of self-report measures for depression and trauma. CONCLUSIONS: Depression symptoms follow a heterogeneous course from before through 6.5 years after deployment with 9.4% experiencing symptom increase, resulting in severe symptoms 6.5 years after deployment. Trajectories are differentially predicted by rank, childhood and adult life trauma as well as neuroticism and PTSD symptoms, illustrating the clinical importance of taking individual differences of symptom course into account.

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

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.

Post-traumatic stress following military deployment: Genetic associations and cross-disorder genetic correlations.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder that occurs with relatively high frequency after deployment to warzones (∼10%). While twin studies have estimated the heritability to be up to 40%, thus indicating a considerable genetic component in the etiology, the biological mechanisms underlying risk and development of PTSD remain unknown. METHODS: Here, we conduct a genome-wide association study (GWAS; N = 2,481) to identify genome regions that associate with PTSD in a highly homogenous, trauma-exposed sample of Danish soldiers deployed to war and conflict zones. We perform integrated analyses of our results with gene-expression and chromatin-contact datasets to prioritized genes. We also leverage on other large GWAS (N>300,000) to investigate genetic correlations between PTSD and other psychiatric disorders and traits. RESULTS: We discover, but do not replicate, one region, 4q31, close to the IL15 gene, which is genome-wide significantly associated with PTSD. We demonstrate that gene-set enrichment, polygenic risk score and genetic correlation analyses show consistent and significant genetic correlations between PTSD and depression, insomnia and schizophrenia. LIMITATIONS: The limited sample size, the lack of replication, and the PTSD case definition by questionnaire are limitations to the study. CONCLUSIONS: Our results suggest that genetic perturbations of inflammatory response may contribute to the risk of PTSD. In addition, shared genetic components contribute to observed correlations between PTSD and depression, insomnia and schizophrenia.

Mental Health Care for Service Members and Their Families Across the Globe.

The U.S. Defense Department partnered with the International Initiative for Mental Health Leadership on effective leadership and operational practices for delivery of mental health (MH) as well as addiction services throughout the world for Service Members (SM) and beneficiaries. A Military Issues Work Group (MIWG) was established in 2011 to focus on challenges experienced by military SM and beneficiaries among countries. The MIWG found common concerns related to MH care delivery to rural and remote beneficiaries. Gaps in access to care were identified and prioritized to explore. This led to better collaboration and understanding of telemental health (TMH) practices and technology applications (apps) which increase access to care for rural and remote SMs and beneficiaries. An assessment of the number of SMs and dependents distant from MH care services in the USA was conducted, as well as an environmental scan for psychological health-focused mobile apps and TMH services geared toward SM, veterans, and beneficiaries. The MIWG is developing a compendium of existing military TMH programs and apps that address MH concerns and extant literature on use of technology to extend global access to care for military members and their families across the world.

Leadership and post-traumatic stress disorder: are soldiers' perceptions of organizational justice during deployment protective?

Background: Soldiers' perception of leadership during military deployment has gained research attention as a potentially modifiable factor to buffer against the development of postdeployment post-traumatic stress disorder (PTSD). Within nonmilitary research, the organizational justice (OJ) framework, i.e. distributive justice, procedural justice (PJ) and interactional justice (IJ), has been found to relate to mental health outcomes. Aspects of OJ may, therefore, be protective against PTSD. Objectives: We examined the prospective relationship between aspects of OJ, namely the perceptions of PJ and IJ by subordinate soldiers without leadership obligations in relationship to immediate superiors and PTSD. Method: Participants were soldiers (n = 245) deployed to Helmand Province in Afghanistan in 2009. Logistic regression procedures were used. The primary analysis measured PTSD cases using the Structured Clinical Interview for DSM-IV-TR Axis-I Disorder (SCID) 2½ years after homecoming. PJ/IJ was measured during deployment with a 6-item composite measure ranging from 0 to 12. Supplementary primary analyses were performed with PJ/IJ measured before and immediately after deployment. A secondary PJ/IJ analysis also tested against four postdeployment measures with the Post-Traumatic Stress Disorder Checklist Civilian (PCL-C) dichotomized at screening symptom levels. Results: Higher levels of perceived PJ/IJ for soldiers without leadership obligations during deployment had a prospective relation (OR = 0.86, 95% CI = 0.75-0.98) with PTSD on the SCID 2½ years after homecoming after adjustment for factors including predeployment PTSD symptoms, trauma and combat exposure, and state affectivity. Similar results were found by measuring PJ/IJ before (OR = 0.83, 95% CI = 0.71-0.95) but not immediately after homecoming (OR = 0.97, 95% CI = 0.85-1.11). A relationship with PTSD symptoms at the screening level at the four measurements of PCL-C was found, but only when predeployment PTSD symptoms were not controlled for. Conclusions: These results suggest that PJ/IJ exercised by superiors in relation to military deployments may protect subordinate soldiers against the development of postdeployment PTSD.

Planteamiento: La percepción del liderazgo de los soldados durante un despliegue militar se ha ganado la atención de la investigación como factor potencialmente modificable para amortiguar el desarrollo del trastorno por estrés postraumático (TEPT) después de un despliegue militar. Dentro de la investigación no militar, se ha encontrado que el marco de justicia organizacional (JO) ­es decir, justicia distributiva, justicia procedimental (JP) y justicia interaccional (JI)­ está relacionado con resultados de salud mental. Algunos aspectos de la JO pueden, por lo tanto, proteger contra el TEPT.Objetivos: Examinamos la relación prospectiva entre los aspectos de la JO, es decir, las percepciones de JP y JI de los soldados subordinados sin obligaciones de liderazgo en relación a sus superiores inmediatos y al TEPT. Método: Los participantes fueron soldados (n = 245) desplegados en la provincia de Helmand en Afganistán en 2009. Se usaron procedimientos de regresión logística. El análisis principal midió los casos de TEPT mediante la Entrevista Clínica Estructurada para los trastorno del Eje I del DSM-IV-TR (SCID, por sus siglas en inglés) dos años y medio después del regreso a casa. Se midieron la JP y la JI durante el despliegue con una medida compuesta de seis elementos que van de 0 a 12. Se realizaron análisis primarios adicionales, midiendo la JP y la JI antes e inmediatamente después del despliegue. Un análisis secundario de la JP y la JI también se comparó con cuatro medidas posteriores al despliegue con la Lista de verificación del trastorno por estrés postraumático civil (PCL-C, por sus siglas en inglés) dicotomizada para los niveles de síntomas en la selección.Resultados: Niveles más altos de percepción de JP / JI en soldados sin obligaciones de liderazgo durante el despliegue tuvieron una relación prospectiva (OR = 0.86, 95% -IC = 0.75­0.98) con el TEPT en el SCID 2½ años después del regreso al hogar por factores que incluían síntomas de TEPT previos al despliegue, exposición al trauma y al combate, y afectividad de estado. Se encontraron resultados similares midiendo la JP y la JI antes (OR = 0,83; IC del 95% = 0,71­0,95) pero no inmediatamente después de la vuelta al hogar (OR = 0,97; IC del 95% = 0,85­1,11). Se encontró una relación con los síntomas de TEPT en el nivel de detección en las cuatro medidas del PCL-C, pero solo cuando no se controlaron los síntomas del TEPT antes del despliegue.Conclusiones: Estos resultados sugieren que la JP y la JI ejercidas por los superiores en relación con los despliegues militares puede proteger a los soldados subordinados de desarrollar un TEPT posterior al despliegue.

Anhedonia and emotional numbing in treatment-seeking veterans: behavioural and electrophysiological responses to reward.

Background: Anhedonia is a common symptom following exposure to traumatic stress and a feature of the PTSD diagnosis. In depression research, anhedonia has been linked to deficits in reward functioning, reflected in behavioural and neural responses. Such deficits following exposure to trauma, however, are not well understood. Objective: The current study aims to estimate the associations between anhedonia, PTSD symptom-clusters and behavioural and electrophysiological responses to reward. Methods: Participants (N = 61) were recruited among Danish treatment-seeking veterans at the Department of Military Psychology in the Danish Defence. Before entering treatment, participants were screened with symptom measurement instruments and participated in a joint behavioural-electrophysiological experiment. The experimental paradigm consisted of a signal-detection task aimed at assessing reward-driven learning. Simultaneous electrophysiological-recordings were analysed to evaluate neural responses upon receiving reward, as indicated by the Feedback-Related Negativity (FRN) component. Result: Anhedonia as conceptualized in depression correlated with behavioural learning (r = -0.28, p = .032). Neither anhedonia nor behavioural learning correlated with FRN. However, the anhedonia symptom cluster of PTSD did correlate with FRN (r = 0.29, p = .023). Extending upon this in an exploratory analysis, the specific PTSD-symptom emotional numbing was found to correlate moderately with FRN (r = 0.38, p = .003). Conclusion: The present data suggest that anhedonia in trauma-exposed individuals is related to the anticipatory aspect of reward, whereas the neural consummatory reward response seems unlinked. Interestingly, emotional numbing in the same population is related to the consummatory phase of reward, correlating with the FRN response. This suggests that anhedonia and emotional numbing in response to trauma might pertain to different phases of reward processing.

Planteamiento: La anhedonia es un síntoma frecuente después de la exposición al estrés traumático y una característica del diagnóstico de TEPT. En la investigación de la depresión, la anhedonia se ha relacionado con los déficits en el funcionamiento de la recompensa, que se refleja en las respuestas conductuales y neuronales. Dichos déficits después de la exposición al trauma, sin embargo, no se entienden bien.Objetivo: El presente estudio tiene como objetivo estimar las asociaciones entre la anhedonia, los grupos de síntomas de TEPT y las respuestas conductuales y electrofisiológicas a la recompensa. Métodos: Los participantes (N = 61) fueron reclutados entre los veteranos daneses que buscaban tratamiento en el Departamento de Psicología Militar de la Defensa Danesa. Antes de empezar al tratamiento, los participantes fueron evaluados con instrumentos de medición de síntomas y participaron en un experimento conjunto electrofisiológico-conductual. El paradigma experimental consistió en una tarea de detección de señales destinada a evaluar el aprendizaje basado en recompensas. Simultáneamente se analizaron las grabaciones de EEG para evaluar las respuestas neurales al recibir la recompensa, según lo indicado por el componente de negatividad relacionada con la retroalimentación (FRN, por sus siglas en inglés).Resultados: La anhedonia, tal como se conceptualizó en la depresión, se correlacionó con el aprendizaje conductual (r = −0.28, p = .032). Ni la anhedonia ni el aprendizaje conductual se correlacionaron con la FRN. Sin embargo, el grupo de síntomas de anhedonia del TEPT se correlacionó con el FRN (r = 0.29, p = .023). Sobre la base de esto en un análisis exploratorio, el entumecimiento emocional específico de los síntomas del TEPT se correlacionó moderadamente con la FRN (r = 0.38, p = .003).Conclusiones: Los datos actuales sugieren que la anhedonia en individuos expuestos al trauma está relacionada con el aspecto anticipatorio de la recompensa, mientras que la respuesta de recompensa neural consumada parece desvinculada. Curiosamente, el adormecimiento emocional en la misma población está relacionado con la fase de recompensa consumada, que se correlaciona con la respuesta FRN. Esto sugiere que la anhedonia y el entumecimiento emocional en respuesta al trauma podrían pertenecer a diferentes fases del procesamiento de la recompensa.

Does size really matter? A multisite study assessing the latent structure of the proposed ICD-11 and DSM-5 diagnostic criteria for PTSD.

Background: Researchers and clinicians within the field of trauma have to choose between different diagnostic descriptions of posttraumatic stress disorder (PTSD) in the DSM-5 and the proposed ICD-11. Several studies support different competing models of the PTSD structure according to both diagnostic systems; however, findings show that the choice of diagnostic systems can affect the estimated prevalence rates. Objectives: The present study aimed to investigate the potential impact of using a large (i.e. the DSM-5) compared to a small (i.e. the ICD-11) diagnostic description of PTSD. In other words, does the size of PTSD really matter? Methods: The aim was investigated by examining differences in diagnostic rates between the two diagnostic systems and independently examining the model fit of the competing DSM-5 and ICD-11 models of PTSD across three trauma samples: university students (N = 4213), chronic pain patients (N = 573), and military personnel (N = 118). Results: Diagnostic rates of PTSD were significantly lower according to the proposed ICD-11 criteria in the university sample, but no significant differences were found for chronic pain patients and military personnel. The proposed ICD-11 three-factor model provided the best fit of the tested ICD-11 models across all samples, whereas the DSM-5 seven-factor Hybrid model provided the best fit in the university and pain samples, and the DSM-5 six-factor Anhedonia model provided the best fit in the military sample of the tested DSM-5 models. Conclusions: The advantages and disadvantages of using a broad or narrow set of symptoms for PTSD can be debated, however, this study demonstrated that choice of diagnostic system may influence the estimated PTSD rates both qualitatively and quantitatively. In the current described diagnostic criteria only the ICD-11 model can reflect the configuration of symptoms satisfactorily. Thus, size does matter when assessing PTSD.

Planteamiento: Los investigadores y clínicos del campo del trauma pronto decidirán entre dos descripciones diagnósticas diferentes del trastorno de estrés postraumático (TEPT) en el DSM-5 y la propuesta CIE-11. Varios estudios apoyan diferentes modelos en competencia sobre la estructura del TEPT en función de ambos sistemas de diagnóstico; sin embargo, los resultados demuestran que la elección de los sistemas de diagnóstico puede afectar las tasas de prevalencia estimadas. Objetivos: y métodos. El presente estudio tenía como objetivo investigar el impacto potencial de usar una descripción del TEPT amplia (es decir, el DSM-5) en comparación con una pequeña (es decir, la CIE-11). En otras palabras, ¿el tamaño del TEPT importa realmente? El objetivo se investigó mediante el examen de las diferencias en las frecuencias de diagnóstico entre los dos sistemas de diagnóstico y examinando de forma independiente cómo se ajustaban los modelos en competencia para el TEPT del DSM-5 y la CIE-11 en tres muestras de trauma: estudiantes universitarios (N = 4213), pacientes con dolor crónico (N = 573) y personal militar (N = 118). Resultados: Las tasas diagnósticas del TEPT fueron significativamente más bajas según los criterios de la propuesta CIE-11 en la muestra universitaria, pero no se encontraron diferencias significativas para los pacientes con dolor crónico y el personal militar. El modelo de tres factores propuesto por la CIE-11 proporcionó el mejor ajuste de los modelos de la CIE-11 que fueron probados en todas las muestras. En cambio, el modelo híbrido de siete factores del DSM-5 proporcionó el mejor ajuste en las muestras universitaria y del dolor, y el modelo de Anhedonia de seis factores del DSM-5 en la muestra militar de los modelos probados del DSM-5. Conclusiones: Se pueden debatir las ventajas y desventajas de utilizar un conjunto amplio o reducido de síntomas para el TEPT; sin embargo, este estudio demostró que la elección del sistema de diagnóstico puede influir en las tasas estimadas del TEPT, tanto cualitativa como cuantitativamente. Al mismo tiempo, parece que, dados los criterios diagnósticos descritos actualmente, solo el modelo de la CIE-11 puede reflejar satisfactoriamente la configuración de los síntomas. Por lo tanto, el tamaño importa cuando se evalúa el TEPT.

Cognitive ability and risk of post-traumatic stress disorder after military deployment: an observational cohort study.

BACKGROUND: Studies of the association between pre-deployment cognitive ability and post-deployment post-traumatic stress disorder (PTSD) have shown mixed results. AIMS: To study the influence of pre-deployment cognitive ability on PTSD symptoms 6-8 months post-deployment in a large population while controlling for pre-deployment education and deployment-related variables. METHOD: Study linking prospective pre-deployment conscription board data with post-deployment self-reported data in 9695 Danish Army personnel deployed to different war zones in 1997-2013. The association between pre-deployment cognitive ability and post-deployment PTSD was investigated using repeated-measure logistic regression models. Two models with cognitive ability score as the main exposure variable were created (model 1 and model 2). Model 1 was only adjusted for pre-deployment variables, while model 2 was adjusted for both pre-deployment and deployment-related variables. RESULTS: When including only variables recorded pre-deployment (cognitive ability score and educational level) and gender (model 1), all variables predicted post-deployment PTSD. When deployment-related variables were added (model 2), this was no longer the case for cognitive ability score. However, when educational level was removed from the model adjusted for deployment-related variables, the association between cognitive ability and post-deployment PTSD became significant. CONCLUSIONS: Pre-deployment lower cognitive ability did not predict post-deployment PTSD independently of educational level after adjustment for deployment-related variables. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Assessing PTSD in the military: Validation of a scale distributed to Danish soldiers after deployment since 1998.

Since 1998, soldiers deployed to war zones with the Danish Defense (≈31,000) have been invited to fill out a questionnaire on post-mission reactions. This provides a unique data source for studying the psychological toll of war. Here, we validate a measure of PTSD-symptoms from the questionnaire. Soldiers from two cohorts deployed to Afghanistan with the International Security Assistance Force (ISAF) in 2009 (ISAF7, N = 334) and 2013 (ISAF15, N = 278) filled out a standard questionnaire (Psychological Reactions following International Missions, PRIM) concerning a range of post-deployment reactions including symptoms of PTSD (PRIM-PTSD). They also filled out a validated measure of PTSD-symptoms in DSM-IV, the PTSD-checklist (PCL). We tested reliability of PRIM-PTSD by estimating Cronbach's alpha, and tested validity by correlating items, clusters, and overall scale with corresponding items in the PCL. Furthermore, we conducted two confirmatory factor analytic models to test the factor structure of PRIM-PTSD, and tested measurement invariance of the selected model. Finally, we established a screening and a clinical cutoff score by application of ROC analysis. We found high internal consistency of the PRIM-PTSD (Cronbach's alpha = 0.88; both cohorts), strong item-item (0.48-0.83), item-cluster (0.43-0.72), cluster-cluster (0.71-0.82) and full-scale (0.86-0.88) correlations between PRIM-PTSD and PCL. The factor analyses showed adequate fit of a one-factor model, which was also found to display strong measurement invariance across cohorts. ROC curve analysis established cutoff scores for screening (sensitivity = 1, specificity = 0.93) and clinical use (sensitivity = 0.71, specificity = 0.98). In conclusion, we find that PRIM-PTSD is a valid measure for assessing PTSD-symptoms in Danish soldiers following deployment.

The influence of pre-deployment cognitive ability on post-traumatic stress disorder symptoms and trajectories: The Danish USPER follow-up study of Afghanistan veterans.

OBJECTIVE: New trajectories of PTSD symptoms have recently been identified in war exposed army veterans. The aim of this army veterans study was to examine whether pre-deployment cognitive ability is associated with the risk of developing PTSD symptoms or non-resilient PTSD trajectories. METHOD: Follow up study in 428 Danish soldiers, deployed to Afghanistan in 2009, who were assessed at six occasions from pre-deployment to three years post-deployment. Pre-deployment vulnerabilities, deployment and homecoming stressors were measured. Pre-deployment cognitive test scores on Børge Priens Prøve (based on logical, verbal, numerical and spatial reasoning) were converted to a mean of 100 and with a standard deviation of 15. RESULTS: Higher pre-deployment cognitive ability scores were associated with lower risk of PTSD symptoms as assessed by the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) 2.5 years post-deployment (OR=0.97; 95% CI 0.95-1.00) after adjustment for educational length, baseline PCL-C score and perceived war-zone stress. Compared to a resilient trajectory, a non-resilient relieved-worsening trajectory (high baseline mental symptoms, being symptom free during deployment and a drastic increase in PTSD symptoms at the final assessments of PTSD symptoms) had significantly lower cognitive scores by a mean difference of 14.5 (95% CI 4.7-24.3). This trajectory (n=9) comprised 26.5% of soldiers with moderate-severe PTSD symptoms 2.5 years post-deployment. CONCLUSION: We confirmed an inverse association between pre-deployment cognitive ability and risk of PTSD symptoms, and observed significantly lower mean pre-deployment cognitive scores in one non-resilient PTSD trajectory. If replicated, this might inform relevant prevention efforts for soldiers at pre-deployment.

Early identification of posttraumatic stress following military deployment: Application of machine learning methods to a prospective study of Danish soldiers.

BACKGROUND: Pre-deployment identification of soldiers at risk for long-term posttraumatic stress psychopathology after home coming is important to guide decisions about deployment. Early post-deployment identification can direct early interventions to those in need and thereby prevents the development of chronic psychopathology. Both hold significant public health benefits given large numbers of deployed soldiers, but has so far not been achieved. Here, we aim to assess the potential for pre- and early post-deployment prediction of resilience or posttraumatic stress development in soldiers by application of machine learning (ML) methods. METHODS: ML feature selection and prediction algorithms were applied to a prospective cohort of 561 Danish soldiers deployed to Afghanistan in 2009 to identify unique risk indicators and forecast long-term posttraumatic stress responses. RESULTS: Robust pre- and early postdeployment risk indicators were identified, and included individual PTSD symptoms as well as total level of PTSD symptoms, previous trauma and treatment, negative emotions, and thought suppression. The predictive performance of these risk indicators combined was assessed by cross-validation. Together, these indicators forecasted long term posttraumatic stress responses with high accuracy (pre-deployment: AUC = 0.84 (95% CI = 0.81-0.87), post-deployment: AUC = 0.88 (95% CI = 0.85-0.91)). LIMITATIONS: This study utilized a previously collected data set and was therefore not designed to exhaust the potential of ML methods. Further, the study relied solely on self-reported measures. CONCLUSIONS: Pre-deployment and early post-deployment identification of risk for long-term posttraumatic psychopathology are feasible and could greatly reduce the public health costs of war.

Community integration after deployment to Afghanistan: a longitudinal investigation of Danish soldiers.

OBJECTIVE: In the years following military deployment, soldiers may experience problems integrating into the community. However, little is known about the nature and prevalence of these problems and if they relate to posttraumatic symptomatology. METHODS: In a prospective, longitudinal study of Danish soldiers deployed to Afghanistan in 2009 (N = 743), we assessed community reintegration difficulties 2.5 years after home coming (study sample: N = 454). Furthermore, symptoms of posttraumatic stress disorder (PTSD) were assessed before, during, and after deployment. Trajectories of PTSD symptoms from a previously published latent growth mixture modeling analysis were used to address whether community reintegration difficulties differ as a result of course and level of PTSD symptoms. RESULTS: Between 3.6 and 18.0% reported to have some, a lot, or extreme difficulties in reintegration domains such as interpersonal functioning, productivity, community involvement, and self-care. Mean level of reintegration difficulties differed significantly across six PTSD symptom trajectories (range 6.35-36.00); with more symptomatic trajectories experiencing greater community reintegration difficulties. CONCLUSIONS: Reintegration difficulties after deployment are present in less than 20% of Danish soldiers who return from Afghanistan. Difficulties are greater in individuals who follow symptomatic PTSD trajectories in the first years following deployment than in those who follow a low-stable trajectory with no or few symptoms.