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263


Letter to the Editor: Posttraumatic stress disorder has genetic overlap with cardiometabolic traits [Letter]

Sumner, J A; Duncan, L E; Wolf, E J; Amstadter, A B; Baker, D G; Beckham, J C; Gelaye, B; Hemmings, S; Kimbrel, N A; Logue, M W; Michopoulos, V; Mitchell, K S; Nievergelt, C; Rothbaum, A; Seedat, S; Shinozaki, G; Vermetten, E
PMCID:5501741
PMID: 28374664
ISSN: 1469-8978
CID: 2616632

Longitudinal changes in glucocorticoid receptor exon 1F methylation and psychopathology after military deployment

Schur, R R; Boks, M P; Rutten, B P F; Daskalakis, N P; de Nijs, L; van Zuiden, M; Kavelaars, A; Heijnen, C J; Joels, M; Kahn, R S; Geuze, E; Vermetten, E; Vinkers, C H
Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucocorticoid receptor exon 1F region (GR-1F) for trauma-related psychopathology. We conducted a longitudinal study to examine GR-1F methylation changes over time in relation to trauma exposure and the development of post-deployment psychopathology. GR-1F methylation (52 loci) was quantified using pyrosequencing in whole blood of 92 military men 1 month before and 6 months after a 4-month deployment period to Afghanistan. GR-1F methylation overall (mean methylation and the number of methylated loci) and functional methylation (methylation at loci associated with GR exon 1F expression) measures were examined. We first investigated the effect of exposure to potentially traumatic events during deployment on these measures. Subsequently, changes in GR-1F methylation were related to changes in mental health problems (total Symptom Checklist-90 score) and posttraumatic stress disorder (PTSD) symptoms (Self-Report Inventory for PTSD). Trauma exposure during deployment was associated with an increase in all methylation measures, but development of mental health problems 6 months after deployment was only significantly associated with an increased functional methylation. Emergence of post-deployment PTSD symptoms was not related to increased functional methylation over time. Pre-deployment methylation levels did not predict post-deployment psychopathology. To our knowledge, this is the first study to prospectively demonstrate trauma-related increases in GR-1F methylation, and it shows that only increases at specific functionally relevant sites predispose for post-deployment psychopathology.
PMCID:5538126
PMID: 28742078
ISSN: 2158-3188
CID: 2653872

Odor-induced recall of emotional memories in PTSD-Review and new paradigm for research

Daniels, Judith K; Vermetten, Eric
It is clinically well known that olfactory intrusions in PTSD can be a disabling phenomena due to the involuntary recall of odor memories. Odorants can trigger involuntary recall of emotional memories as well have the potential to help diminishing emotional arousal as grounding stimuli. Despite major advances in our understanding of the function of olfactory system, the study of the relation of olfaction and emotional memory is still relatively scarce. Odor memory is long thought to be different than other types of memories such as verbal or visual memories, being more strongly engraved and more closely related to strong emotions. Brain areas mediating smell memory including orbitofrontal cortex and other parts of medial prefrontal cortex, hippocampus and amygdala, have been implicated in learning and memory and are part of a neural circuitry that is involved in PTSD. The olfactory cortex itself also plays an important role in emotional processing. Clinical observations support the notion that odor-evoked memories can play a role in the symptomatology of PTSD. This paper reviews a re-emerging body of science linking odor processing to emotional processing in PTSD using the calming and grounding effect of odors as well as the use of odors in augmented exposure therapy. This results in converging evidence that olfaction is an excellent model for studying many questions germane to the field of human emotional memory processing.
PMID: 27511295
ISSN: 1090-2430
CID: 2514142

Unintended Consequences of Changing the Definition of Posttraumatic Stress Disorder in DSM-5: Critique and Call for Action

Hoge, Charles W; Yehuda, Rachel; Castro, Carl A; McFarlane, Alexander C; Vermetten, Eric; Jetly, Rakesh; Koenen, Karestan C; Greenberg, Neil; Shalev, Arieh Y; Rauch, Sheila A M; Marmar, Charles R; Rothbaum, Barbara O
PMID: 27224895
ISSN: 2168-6238
CID: 2115032

Epigenome-wide association of PTSD from heterogeneous cohorts with a common multi-site analysis pipeline [Meeting Abstract]

Smith, A; Ratanatharathorn, A; Boks, M; Logue, M; Maihofer, A; Kilaru, V; Garrett, M; Guffanti, G; Vermetten, E; Koenen, K; Aiello, A; Baker, D; Hauser, M; Kimbrel, N; Dennis, M; Ashley-Koch, A; Luft, B; Bromet, E; Miller, M; Ressler, K; Uddin, M; Nievergelt, C
Background: Post-traumatic stress disorder (PTSD) results from trauma, but not all individuals develop PTSD after trauma. Differences in susceptibility to PTSD may be related to epigenetic differences between cases and trauma-exposed controls that can provide insight into the biological processes underlying PTSD and may serve as biological indicators of PTSD risk or resilience. Methods: The PGC-PTSD Epigenetics Workgroup combined epigenome-wide data from a diverse group of military and civilian studies to conduct a cross-sectional meta-analysis of current PTSD in >445 cases and >700 trauma-exposed controls. For all samples, DNA methylation was measured in whole blood using the Infinium HumanMethylation450 BeadChip. A common pipeline was developed for quality control, data normalization and association testing. Using this pipeline, EWAS was performed on each cohort followed by meta-analysis using inverse normal p-value combination and false discovery rate (FDR) estimation. Results: There were substantial differences in the results from each cohort. No CpG site remained significant after correction for multiple testing, but the top results included CpG sites (7.7e-7
EMBASE:72256553
ISSN: 0006-3223
CID: 2103582

Emotional Reactions and Moral Judgment: The Effects of Morally Challenging Interactions in Military Operations

de Graaff, Miriam C; Schut, Michelle; Verweij, Desiree EM; Vermetten, Eric; Giebels, Ellen
This study explores the association between different types of morally challenging interactions during military deployment and response strategies (e.g., moral justification), as well as the mediating role of moral emotions. Interviews with Dutch servicemen who participated in military operations (e.g., in Afghanistan, Angola; N = 45) were content coded. We found a relationship between local-cultural and team-related interactions and moral justification; these effects were mediated by other-condemning emotions. Similarly, other-condemning emotions mediated the relationship between local-cultural interactions and relativism. This study points at the importance of other-condemning emotions in shaping military reactions to frequently occurring morally challenging interactions.
ISI:000366611000002
ISSN: 1532-7019
CID: 2345012

Post-traumatic stress disorder

Yehuda, Rachel; Hoge, Charles W; McFarlane, Alexander C; Vermetten, Eric; Lanius, Ruth A; Nievergelt, Caroline M; Hobfoll, Stevan E; Koenen, Karestan C; Neylan, Thomas C; Hyman, Steven E
Post-traumatic stress disorder (PTSD) occurs in 5-10% of the population and is twice as common in women as in men. Although trauma exposure is the precipitating event for PTSD to develop, biological and psychosocial risk factors are increasingly viewed as predictors of symptom onset, severity and chronicity. PTSD affects multiple biological systems, such as brain circuitry and neurochemistry, and cellular, immune, endocrine and metabolic function. Treatment approaches involve a combination of medications and psychotherapy, with psychotherapy overall showing greatest efficacy. Studies of PTSD pathophysiology initially focused on the psychophysiology and neurobiology of stress responses, and the acquisition and the extinction of fear memories. However, increasing emphasis is being placed on identifying factors that explain individual differences in responses to trauma and promotion of resilience, such as genetic and social factors, brain developmental processes, cumulative biological and psychological effects of early childhood and other stressful lifetime events. The field of PTSD is currently challenged by fluctuations in diagnostic criteria, which have implications for epidemiological, biological, genetic and treatment studies. However, the advent of new biological methodologies offers the possibility of large-scale approaches to heterogeneous and genetically complex brain disorders, and provides optimism that individualized approaches to diagnosis and treatment will be discovered.
PMID: 27189040
ISSN: 2056-676x
CID: 2111742

Longitudinal measures of hostility in deployed military personnel

Heesink, Lieke; Rademaker, Arthur; Vermetten, Eric; Geuze, Elbert; Kleber, Rolf
Increases in anger and hostility are commonly found after military deployment. However, it is unknown how anger and hostility develop over time, and which veterans are more at risk for developing these complaints. Data of 745 veterans one month before deployment to Afghanistan and one, six, twelve and 24 months after deployment were analyzed in a growth model. Growth mixture modeling revealed four classes based on their growth in hostility. Most of the participants belonged to a low-hostile group or a mild-hostile group that remained stable over time. Two smaller groups were identified that displayed increase in hostility ratings after deployment. The first showed an immediate increase after deployment. The second showed a delayed increase between twelve and 24 months after deployment. No groups were identified that displayed a decrease of hostility symptoms over time. Multinomial logistic regression was applied to predict group membership by age, education, early trauma, deployment stressors and personality factors. This study gains more insight into the course of hostility over time, and identifies risk factors for the progression of hostility.
PMID: 26165965
ISSN: 1872-7123
CID: 2911962

Impact of combat events on first responders: Experiences of the armed conflict in Uruzgan, Afghanistan

Hoencamp, Rigo; Idenburg, Floris J; Vermetten, Eric; Tan, Edward; Plat, Marie-Christine; Hoencamp, Erik; Leenen, Luke P H; Hamming, Jaap F
INTRODUCTION: Care for battle casualties demands special skills from medics, nurses, and tactical commanders. To date, no inventory has been performed evaluating the first responders (medics, nurses and tactical commanders) around battle casualties. METHOD: This observational cohort study was conducted amongst the first responders (n=195) who were deployed to Southern Afghanistan (2009-2010) in three Marine companies. The survey focused on four main topics: (1) participants general background, (2) exposure to combat (casualty) situations, (3) self-perceived quality of care (1 [low]-10 [high]) in the pre-hospital phase, and (4) the effects of combat stressors on professional skills and social environment using the Post Deployment Reintegration Scale (PDRS) and the Impact of Event Scale-Revised (IES-R). RESULTS: 71% of the eligible Dutch tactical commanders, medics, and nurses participated in this survey. Most (14/16) medics and nurses scored their pre-deployment training as sufficient The overall self-perceived quality of care score was above average (7.8). Most (80%) of the participants were exposed to battle casualties. There were no significant differences regarding rank, gender, age and military task using the impact of event scale and PDRS, except for a worse score on the work negative, family positive and personal positive subscales (p<0.05) in the PDRS for the first responders in comparison to the armed forces norm score. CONCLUSION: The quality of care in the pre-hospital phase was considered adequate, symptoms of post-traumatic stress in this group was low. Active involvement of co-combatants and the social support network are essential in adaption after exposure to combat events. Further research is necessary to identity predisposing preventable high stress factors, and to compose a "waterproof" aftercare programme.
PMID: 25548112
ISSN: 0020-1383
CID: 1469732

Prevalence of mental health symptoms in Dutch military personnel returning from deployment to Afghanistan: A 2-year longitudinal analysis

Reijnen, A; Rademaker, A R; Vermetten, E; Geuze, E
OBJECTIVE: Recent studies in troops deployed to Iraq and Afghanistan have shown that combat exposure and exposure to deployment-related stressors increase the risk for the development of mental health symptoms. The aim of this study is to assess the prevalence of mental health symptoms in a cohort of Dutch military personnel prior to and at multiple time-points after deployment. METHODS: Military personnel (n=994) completed various questionnaires at 5 time-points; starting prior to deployment and following the same cohort at 1 and 6months and 1 and 2years after their return from Afghanistan. RESULTS: The prevalence of symptoms of fatigue, PTSD, hostility, depression and anxiety was found to significantly increase after deployment compared with pre-deployment rates. As opposed to depressive symptoms and fatigue, the prevalence of PTSD was found to decrease after the 6-month assessment. The prevalence of sleeping problems and hostility remained relatively stable. CONCLUSIONS: The prevalence of mental health symptoms in military personnel increases after deployment, however, symptoms progression over time appears to be specific for various mental health symptoms. Comprehensive screening and monitoring for a wide range of mental health symptoms at multiple time-points after deployment is essential for early detection and to provide opportunities for intervention. DECLARATION OF INTEREST: This project was funded by the Dutch Ministry of Defence.
PMID: 25195152
ISSN: 0924-9338
CID: 1469652