Faculty Bibliography

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.

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.

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.

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.

OBJECTIVE: Combat stress exposed soldiers may respond to post-deployment stressful life events (SLE) with increases in symptoms of posttraumatic stress disorder (PTSD), consistent with a model of stress sensitization. Several lines of research point to sensitization as a model to describe the relations between exposure to traumatic events, subsequent SLE, and symptoms of PTSD. Based on previous findings we hypothesized that immune activation, measured as a high in vitro capacity of leukocytes to produce cytokines upon stimulation, underlies stress sensitization. METHODS: We assessed mitogen-induced cytokine production at 1 month, SLE at 1 year, and PTSD symptoms from 1 month up to 2 years post-deployment in soldiers returned from deployment to Afghanistan (N=693). Exploratory structural equation modeling as well as latent growth models were applied. RESULTS: The data demonstrated significant three-way interaction effects of combat stress exposure, cytokine production, and post-deployment SLE on linear change in PTSD symptoms over the first 2 years following return from deployment. In soldiers reporting high combat stress exposure, both high mitogen-stimulated T-cell cytokine production and high innate cytokine production were associated with increases in PTSD symptoms in response to post-deployment SLE. In low combat stress exposed soldiers as well as those with low cytokine production, post-deployment SLE were not associated with increases in PTSD symptoms. CONCLUSION: High stimulated T-cell and innate cytokine production may contribute to stress sensitization in recently deployed, high combat stress exposed soldiers. These findings suggest that detecting and eventually normalizing immune activation may potentially complement future strategies to prevent progression of PTSD symptoms following return from deployment.

OBJECTIVE: There is limited evidence on the association of the activity of HPG-axis with stress and symptoms of stress-related disorders. The aim of the current study was to assess the effect of deployment to a combat zone on plasma testosterone levels, and the possible association with the development of symptoms of posttraumatic stress disorder (PTSD). METHODS: A total of 918 males were included in the study before deployment to a combat zone in Afghanistan. The effect of deployment on testosterone was longitudinally assessed; starting prior to deployment and follow-up assessments were preformed at 1 and 6 months after return. Furthermore, the association with PTSD symptoms reported at 1 and 2 years post-deployment was assessed. RESULTS: Plasma testosterone levels were significantly increased after deployment compared with pre-deployment levels. Although no difference was found between individuals reporting high or low levels of PTSD symptoms, pre-deployment testosterone levels predicted the development of PTSD symptoms at 1 and 2 years post-deployment. CONCLUSION: This study provides evidence that not the alterations in testosterone levels shortly after deployment, but the pre-deployment testosterone levels are associated with PTSD symptoms, which is of value in the identification of biological vulnerability factors for the development of PTSD.

Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular ageing will show increased ageing. We expect that particularly in individuals that developed symptoms of post-traumatic stress disorder (PTSD) increases in these ageing parameters would stand out. From an existing longitudinal cohort study, ninety-six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self-Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19-item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator procedure. The association of trauma with telomere length was in the expected direction but not significant (B=-10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p=0.018). In concordance, trauma significantly accelerated epigenetic ageing (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic ageing (B=-0.10, p=0.044). Blood cell count, medication and premorbid early life trauma exposure did not confound the results. Overall, in this longitudinal study of military personnel deployed to Afghanistan we show an acceleration of ageing by trauma. However, development of PTSD symptoms was associated with telomere lengthening and reversed epigenetic ageing. These findings warrant further study of a perhaps dysfunctional compensatory cellular ageing reversal in PTSD.

Deployed soldiers are at risk of developing stress-related conditions, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and severe fatigue. We previously observed condition- and cell-specific differences in sensitivity of immune cells for regulation by glucocorticoids (GCs) pre-deployment between male soldiers with and without subsequent development of high levels of these stress-related symptoms. Here we investigated whether these pre-deployment dysregulations in GC-sensitivity of immune cells persisted after return from military deployment. In a prospective, longitudinal study including 721 male and female soldiers, the in vitro GC-sensitivity of monocytes and T-cells was assessed prior to deployment and one and six months post-deployment. Differences in the longitudinal course of sensitivity for regulation by dexamethasone (DEX) of LPS-stimulated TNF-alpha production and PHA-stimulated T-cell proliferation between soldiers with and without subsequent symptom development were investigated using linear mixed models. Within the whole group, DEX-sensitivity of monocytes was significantly decreased at six months post-deployment compared to the assessments pre-deployment and one month post-deployment. The DEX-sensitivity of T-cells did not significantly change over time. Participants developing high levels of PTSD symptoms showed high DEX-sensitivity of T-cells, while participants developing high levels of depressive symptoms showed low DEX-sensitivity of T-cells before deployment that persisted at the two time points after return. In addition, participants developing severe fatigue had low DEX-sensitivity of monocytes at all assessments. Our finding that the previously observed pre-deployment group differences in peripheral GC-sensitivity persisted until at least six months after return indicates that in vitro GC-sensitivity of T-cells and monocytes may represent a persistent biological vulnerability factor for development of stress-related conditions PTSD, depression and fatigue.

BACKGROUND: A subgroup of servicemen can be identified that seek a disproportionally amount of health care in comparison to diagnostic and therapeutic perspectives. This group can be identified on the basis of an absence of a structural medical explanation for their symptoms. The symptoms manifest predominantly as fatigue and pain, and are often chronic. Patients with medical unexplained medical symptoms (MUPS) often have multiple and complex problems that would be best treated by a multidisciplinary team of medical specialists and paramedics. The military is characterized by high loyalty towards peers and leadership, leading to neglect for personal care. OBJECTIVE: While consensus on the biological basis for these complaints is lacking, awareness on the need for effective treatments for this patient group is high. METHOD: Based on reviews, expert recommendations and clinical demand, a specialized treatment program for soldiers with MUPS has recently been developed and implemented in the system of health care in the Netherlands Armed Forces. We developed a functional rehabilitation program with blended care elements of cognitive behavioral therapy (CBT), physical therapy, case management, and psychoeducation, embedded in a day treatment setting. RESULTS: The program received high scores on participant as well as team satisfaction. The program is illustrated by two clinical vignettes. CONCLUSION: The blended care program for MUPS that focused on allostatic load awareness offered a more holistic and preventive approach that contributed to a reduction of unnecessary medical consumption, and increased job participation. We recommend that the development of guidelines for diagnoses and treatment of these complaints in military settings will improve the quality of patient care, reduce disability, facilitate reintegration, and encourage scientific research.