Faculty Bibliography

Although the symptoms of Post-Traumatic Stress Disorder (PTSD) in the general and military population seem very similar, combat-related PTSD (cr-PTSD) is typically thought to be more severe due to the repeated and prolonged exposure of traumatic events. Therapeutic adherence is reported a problem in military populations compromising treatment efficacy. Therefore, a new potential supplementary treatment is specially designed for patients with cr-PTSD. This intervention is called Military Motion Memory Desensitization and Reprocessing (3MDR). The treatment incorporates key elements of successful treatments as Virtual Reality Exposure (VRE) and Eye Movement Desensitization Reprocessing (EMDR) and adds motion to the condition. We aimed at designing a treatment procedure that preserved dual task processing principle, yet introduced new engagement by performing the desensitization during motion by to walking on a treadmill. Moreover, we aimed at exposure to real high-affect pictures of deployment setting. Subjects walk a repetitive cycle while walking and viewing high affect pictures of deployment scenes. Dual task processing was maintained by an oscillating ball. Aspects of presence are adhered to, to maximize possible positive outcome. METHOD: Two veterans with chronic PTSD, received four weekly sessions of 3MDR therapy. The indicator of effectiveness was difference in CAPS (Clinical Administrated PTSD Scale)-score. The treatment was designed on the Computer Assisted Rehabilitation Environment (CAREN) facility. RESULTS: The 3MDR treatment did further decrease PTSD symptoms. Patients were highly satisfied about the treatment and had no attention to drop out. CONCLUSION: The results of the two cases suggest that the 3MDR treatment is a successful, more additional treatment that goes further into the patients affect where other treatment may stagnate. The presence was highly appreciated. Further research with more patients needs to be performed to obtain more reliable results.

BACKGROUND: In this report we describe the development and use of a web portal in the aftermath of the 2004 tsunami. This large scale disaster confronted many displaced people with death, despair and need for information and support. Awareness and insight in the emotional impact of disasters can provide opportunities for surveillance and early treatment. Moreover, online support systems can contribute to community building, empowerment of victims and resilience. OBJECTIVE: We evaluate the development and use of a multilingual web portal that combined a platform for information, emotional support, self assessment and referral with research opportunities. The rapid development, use, advantages, difficulties and learning points are discussed. METHODS: A multidisciplinary working group from the University Medical Centre Utrecht, the Major Incident Hospital and the Central Military Hospital developed a web portal for tsunami victims. The webportal combined: (1) a forum aimed at community building, (2) self assessment tools that in the same time function as a reseach survey, (3) e-consultation, and (4) an information portal. RESULTS: Within 3 weeks after the tsunami, the working group launched an open, online service (www.TISEI.org. Tsunami Intrenational Survey on Emotional Impact) to foster community) support in the aftermath of the disaster. It combined four functionalities that were earlier previously only used separately. The portal had over 36.800 unique visitors in the first two years. At least 31% (144/464) percent of the Dutch surviving victims could be reached for a survey through the site. The TISEI-environment was available in 15 languages and visitors came from all over the world. Ninety-five percent of all visitors came from Europe or the United States. Subsequent to immediate disaster support, the web portal also served as a memorial archive for anniversary meetings and follow-up incentives. Difficulties we experienced were lack of funding, time pressure, victim-anonymisation, international collaboration and long term maintenance. CONCLUSIONS: A multilingual website with combined modalities for emotional care and research after a natural disaster proved feasible. Web based services like www.TISEI.org in the aftermath of mass disasters can help community building and deliver low level, patient centred and easily accessible information and care. A multilingual website with combined modalities for emotional care and research after a natural disaster proved feasible. Growing Internet penetration world wide and especially the rapid expansion and influence of online communities enables delivery of care and perform research with the internetInternet as a platform. The unpredictable nature of disaster does put time pressure on the development of online solutions and influenced the yield of our site. This highlights the necessity of developing methods and (inter) national collaborations in advance, secure funding, and learn from earlier initiatives.

INTRODUCTION: Individuals who are exposed to a traumatic event are at increased risk of developing psychiatric disorders such as posttraumatic stress disorder (PTSD). Studies have shown that increased amygdala activity is frequently found in patients with PTSD. In addition, pre-trauma glucocorticoid receptor (GR) number in peripheral blood mononuclear cells (PBMCs) has been found to be a significant predictor for the development of PTSD symptoms. Research in rodents has shown that the response of basolateral amygdala neurons to corticosterone is mediated by GR. However, to the best of our knowledge, no previous study has investigated GR number in PBMCs and amygdala function in humans. METHODS: To investigate whether peripheral GR number is related to amygdala functioning, we assessed GR number in PBMCs of healthy soldiers before their deployment to Afghanistan. Amygdala functioning was assessed with fMRI before and after deployment. RESULTS: We found that pre-deployment GR number was significantly negatively correlated to pre-deployment amygdala activity. More importantly, pre-deployment GR number predicted the increase in amygdala activity by deployment. DISCUSSION: Our results demonstrate that peripheral GR number is associated with amygdala functioning and predicts the increase in amygdala activity following military deployment in healthy individuals who did not develop PTSD. It is uncertain how this relationship is mediated mechanistically, but future studies should examine the relation of GR and amygdala activity to determine whether this is part of a common pathway leading to increased vulnerability to stress-related disorders.

AIM: Posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and severe fatigue may develop in response to severe stress and trauma. These conditions have all been shown to be associated with altered sensitivity of leukocytes for regulation by glucocorticoids (GCs). However, it remains unknown whether sensitivity of leukocytes for GCs is a pre-existing vulnerability factor, or whether GC-sensitivity of leukocytes alters as a consequence of stress and stress-related conditions. Our aim was to investigate whether sensitivity of T-cells and monocytes for regulation by GCs (i.e. dexamethasone: DEX) assessed before military deployment predicts high levels of PTSD, depressive, and/or fatigue symptoms 6 months after return from deployment. METHODS: We included 526 male military personnel before deployment to Afghanistan. Logistic regression analysis was performed to predict fatigue, depressive, and PTSD symptoms 6 months after deployment based on sensitivity of LPS-induced TNF-alpha production and PHA-induced T-cell proliferation to DEX-inhibition before deployment. RESULTS: Severe fatigue 6 months after deployment was independently associated with low DEX-sensitivity of monocyte TNF-alpha production before deployment. A high level of depressive symptoms after deployment was independently associated with a low DEX-sensitivity of T-cell proliferation. In contrast, a high level of PTSD symptoms after deployment was independently associated with a high DEX-sensitivity of T-cell proliferation before deployment, but only in individuals who reported PTSD symptoms without depressive symptoms. The predictive value of DEX-sensitivity was independent of childhood trauma and GR number, GR subtype and GR target gene mRNA expression in leukocytes. CONCLUSIONS: We present here for the first time that the sensitivity of leukocytes for GCs prior to deployment is a predictive factor for the development of PTSD, depressive and fatigue symptomatology in response to deployment. Notably, PTSD, depressive and fatigue symptoms were differentially associated with GC-sensitivity of monocytes and T-cells and therefore may have different biological underpinnings.

Prolonged stress can have long-lasting effects on cognition. Animal models suggest that deficits in executive functioning could result from alterations within the mesofrontal circuit. We investigated this hypothesis in soldiers before and after deployment to Afghanistan and a control group using functional and diffusion tensor imaging. Combat stress reduced midbrain activity and integrity, which was associated to compromised sustained attention. Long-term follow-up showed that the functional and structural changes had normalized within 1.5 y. In contrast, combat stress induced a persistent reduction in functional connectivity between the midbrain and prefrontal cortex. These results demonstrate that combat stress has adverse effects on the human mesofrontal circuit and suggests that these alterations are partially reversible.

BACKGROUND: It has been suggested that pro-inflammatory cytokine signaling to the brain may contribute to severe fatigue. We propose that not only the level of circulating cytokines, but also increased reactivity of target cells to cytokines contributes to the effect of cytokines on behavior. Based on this concept, we assessed the reactivity of peripheral blood cells to IL-1beta in vitro as a novel approach to investigate whether severe fatigue is associated with increased pro-inflammatory signaling. METHODS: We included 504 soldiers before deployment to a combat-zone. We examined fatigue severity and the response to in vitro stimulation with IL-1beta prior to deployment (T0), and 1 (T1) and 6 months (T2) after deployment. IL-8 production was used as read-out. As a control we determined LPS-induced IL-8 production. The presence of severe fatigue was assessed with the Checklist Individual Strength (CIS-20R). Differences in dose-response and the longitudinal course of IL-1beta and LPS-induced IL-8 production and fatigue severity were investigated using repeated measures ANOVA. RESULTS: At T2, the group who had developed severe fatigue (n = 65) had significantly higher IL-1beta-induced IL-8 production than the non-fatigued group (n = 439). This group difference was not present at T0, but developed over time. Longitudinal analysis revealed that in the non-fatigued group, IL-1beta-induced IL-8 production decreased over time, while IL-1beta-induced IL-8 production in the fatigued group had not decreased. To determine whether the observed group difference was specific for IL-1beta reactivity, we also analyzed longitudinal LPS-induced IL-8 production. We did not observe a group difference in LPS-induced IL-8 production. CONCLUSIONS: Collectively, our findings indicate that severe fatigue is associated with a higher reactivity to IL-1beta. We propose that assessment of the reactivity of the immune system to IL-1beta may represent a promising novel method to investigate the association between behavioral abnormalities and pro-inflammatory cytokine signaling.

BACKGROUND: Clinical and neurobiological evidence for a dissociative subtype of posttraumatic stress disorder (PTSD) has recently been documented. A dissociative subtype of PTSD is being considered for inclusion in the forthcoming Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) to address the symptoms of depersonalization and derealization found among a subset of patients with PTSD. This article reviews research related to the dissociative subtype including antecedent, concurrent, and predictive validators as well as the rationale for recommending the dissociative subtype. METHODS: The relevant literature pertaining to the dissociative subtype of PTSD was reviewed. RESULTS: Latent class analyses point toward a specific subtype of PTSD consisting of symptoms of depersonalization and derealization in both veteran and civilian samples of PTSD. Compared to individuals with PTSD, those with the dissociative subtype of PTSD also exhibit a different pattern of neurobiological response to symptom provocation as well as a differential response to current cognitive behavioral treatment designed for PTSD. CONCLUSIONS: We recommend that consideration be given to adding a dissociative subtype of PTSD in the revision of the DSM. This facilitates more accurate analysis of different phenotypes of PTSD, assist in treatment planning that is informed by considering the degree of patients' dissociativity, will improve treatment outcome, and will lead to much-needed research about the prevalence, symptomatology, neurobiology, and treatment of individuals with the dissociative subtype of PTSD.