Faculty Bibliography

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.

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.

Given the unique context of warzone engagement, which may include chronic threat, multiple and lengthy deployments, and loss, there is a need to understand whether and to what extent knowledge about PTSD derived from studies of civilian trauma exposure is generalizeable to the military. This special issue on PTSD in the military addresses a range of issues and debates related to mental health in military personnel and combat veterans. This article provides an overview of the issues covered in selected contributions that have been assembled for a special volume to consider issues unique to the military. Several leading scholars and military experts have contributed papers regarding: 1) prevalence rates of PTSD and other post-deployment mental health problems in different NATO countries, 2) the search for biomarkers of PTSD and the potential applications of such findings, and 3) prevention and intervention approaches for service members and veterans. The volume includes studies that highlight the divergence in prevalence rates of PTSD and other post-deployment mental health problems across nations and that discuss potential causes and implications. Included studies also provide an overview of research conducted in military or Veteran's Affairs settings, and overarching reviews of military-wide approaches to research, promotion of resilience, and mental health interventions in the Unites States and across NATO and allied ISAF partners.

BACKGROUND: The North Atlantic Treaty Organization (NATO) coalition forces remain heavily committed on combat operations overseas. Understanding the prevalence and characteristics of battlefield injury of coalition partners is vital to combat casualty care performance improvement. The aim of this systematic review was to evaluate the prevalence and characteristics of battle casualties from NATO coalition partners in Iraq and Afghanistan. The primary outcome was mechanism of injury and the secondary outcome anatomical distribution of wounds. METHODS: This systematic review was performed based on all cohort studies concerning prevalence and characteristics of battlefield injury of coalition forces from Iraq and Afghanistan up to December 20th 2013. Studies were rated on the level of evidence provided according to criteria by the Centre for Evidence Based Medicine in Oxford. The methodological quality of observational comparative studies was assessed by the modified Newcastle-Ottawa Scale. RESULTS: Eight published articles, encompassing a total of n=19,750 battle casualties, were systematically analyzed to achieve a summated outcome. There was heterogeneity among the included studies and there were major differences in inclusion and exclusion criteria regarding the target population among the included trials, introducing bias. The overall distribution in mechanism of injury was 18% gunshot wounds, 72% explosions and other 10%. The overall anatomical distribution of wounds was head and neck 31%, truncal 27%, extremity 39% and other 3%. CONCLUSIONS: The mechanism of injury and anatomical distribution of wounds observed in the published articles by NATO coalition partners regarding Iraq and Afghanistan differ from previous campaigns. There was a significant increase in the use of explosive mechanisms and a significant increase in the head and neck region compared with previous wars.

Several lines of research have demonstrated that memories for fearful events become transiently labile upon re-exposure. Activation of molecular mechanisms is required in order to maintain retrieved information. This process is called reconsolidation. Targeting reconsolidation - as in exposure-based psychotherapy - offers therefore a potentially interesting tool to manipulate fear memories, and subsequently to treat disorders such as post-traumatic stress disorder (PTSD). In this paper we discuss the evidence for reconsolidation in rodents and humans and highlight recent studies in which clinical research on normal and abnormal fear extinction reduction of the expression of fear was obtained by targeting the process of reconsolidation. We conclude that reconsolidation presents an interesting opportunity to modify or alter fear and fear-related memories. More clinical research on normal and abnormal fear extinction is required.

BACKGROUND: Military deployment to combat zones puts military personnel to a number of physical and mental challenges that may adversely affect mental health. Until now, few studies have been performed in Europe on mental health utilization after military deployment. OBJECTIVE: We compared the incidence of mental health consultations with the Military Mental Health Service (MMHS) of military deployed to Afghanistan to that of non-deployed military personnel. METHOD: We assessed utilization of the MMHS by the full cohort of the Netherlands Armed Forces enlisted between 2008 and 2010 through linkage of mental health and human resource information systems. RESULTS: The total population consisted of 50,508 military (18,233 deployed, 32,275 non-deployed), who accounted for 1,906 new consultations with the MMHS. The follow-up was limited to the first 2 years following deployment. We observed higher mental health care utilization in deployed vs. non-deployed military personnel; hazard ratio (HR), adjusted for sex, military branch and time in service, 1.84 [95% CI 1.61-2.11] in the first and 1.28 [1.09-1.49] in the second year after deployment. An increased risk of adjustment disorders (HR 2.59 [2.02-3.32] and 1.74 [1.30-2.32]) and of anxiety disorders (2.22 [1.52-3.25] and 2.28 [1.50-3.45]) including posttraumatic stress disorder (5.15 [2.55-10.40] and 5.28 [2.42-11.50]), but not of mood disorders (1.33 [0.90-1.97] and 1.11 [0.68-1.82]), was observed in deployed personnel in the first- and second-year post-deployment, respectively. Military personnel deployed in a unit with a higher risk of confrontation with potentially traumatic events had a higher HR (2.13 [1.84-2.47] and 1.40 [1.18-1.67]). CONCLUSIONS: Though absolute risk was low, in the first and second year following deployment to Afghanistan there was an 80 and 30% higher risk for mental health problems resulting in a consultation with the Dutch MMHS compared to military never deployed to Afghanistan. These observations underscore the need for an adequate mental health infrastructure for those returning from deployment.

Psychological trauma can have devastating consequences on emotion regulatory capacities and lead to dissociative processes that provide subjective detachment from overwhelming emotional experience during and in the aftermath of trauma. Dissociation is a complex phenomenon that comprises a host of symptoms and factors, including depersonalization, derealization, time distortion, dissociative flashbacks, and alterations in the perception of the self. Dissociation occurs in up to two thirds of patients with borderline personality disorder (BPD). The neurobiology of traumatic dissociation has demonstrated a heterogeneity in posttraumatic stress symptoms that, over time, can result in different types of dysregulated emotional states. This review links the concepts of trauma and dissociation to BPD by illustrating different forms of emotional dysregulation and their clinical relevance to patients with BPD.