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van Zuiden M.,University Utrecht | van Zuiden M.,Research Center Military Mental Health | Kavelaars A.,University Utrecht | Kavelaars A.,University of Illinois at Urbana - Champaign | And 7 more authors.
Journal of Psychiatric Research | Year: 2011

Few prospective studies on pre-trauma predictors for subsequent development of posttraumatic stress disorder (PTSD) have been conducted. In this study we prospectively investigated whether pre-deployment personality and the cortisol awakening response (CAR) predicted development of PTSD symptoms in response to military deployment. Furthermore, we hypothesized that potential effects of age, childhood trauma and previous deployment on development of PTSD symptoms were mediated via pre-deployment personality, CAR and PTSD symptoms.Path analysis was performed on data from 470 male soldiers collected before and six months after a 4-month deployment to Afghanistan. Before deployment, personality was assessed with the short-form Temperament-Character Inventory and the Cook-Medley Hostility scale. In addition, pre-deployment saliva sampling for assessment of the CAR was performed immediately after awakening and 15, 30 and 60. min thereafter.Pre-deployment high hostility and low self-directedness represented intrinsic vulnerabilities for development of PTSD symptoms after deployment. The CAR assessed before deployment did not predict PTSD symptoms after deployment. Pre-deployment low-to-moderate PTSD symptoms were associated with PTSD symptoms after deployment. As hypothesized, the effects of age and childhood trauma on PTSD symptoms after deployment were mediated via personality and pre-deployment PTSD symptoms. However, the number of previous deployments was not related to development of PTSD symptoms. The total model explained 24% of variance in PTSD symptoms after military deployment. © 2010 Elsevier Ltd.


Smid G.E.,Foundation Centrum45 Arq | Kleber R.J.,Foundation Centrum45 Arq | Kleber R.J.,University Utrecht | Rademaker A.R.,Research Center Military Mental Health | And 5 more authors.
Social Psychiatry and Psychiatric Epidemiology | Year: 2013

Purpose: Military personnel exposed to combat are at risk for experiencing post-traumatic distress that can progress over time following deployment. We hypothesized that progression of post-traumatic distress may be related to enhanced susceptibility to post-deployment stressors. This study aimed at examining the concept of stress sensitization prospectively in a sample of Dutch military personnel deployed in support of the conflicts in Afghanistan. Method: In a cohort of soldiers (N = 814), symptoms of post-traumatic stress disorder (PTSD) were assessed before deployment as well as 2, 7, 14, and 26 months (N = 433; 53 %) after their return. Data were analyzed using latent growth modeling. Using multiple group analysis, we examined whether high combat stress exposure during deployment moderated the relation between post-deployment stressors and linear change in post-traumatic distress after deployment. Results: A higher baseline level of post-traumatic distress was associated with more early life stressors (standardized regression coefficient = 0.30, p < 0.001). In addition, a stronger increase in posttraumatic distress during deployment was associated with more deployment stressors (standardized coefficient = 0.21, p < 0.001). A steeper linear increase in posttraumatic distress post-deployment (from 2 to 26 months) was predicted by more post-deployment stressors (standardized coefficient = 0.29, p < 0.001) in high combat stress exposed soldiers, but not in a less combat stress exposed group. The group difference in the predictive effect of post-deployment stressors on progression of post-traumatic distress was significant (χ2(1) = 7.85, p = 0.005). Conclusions: Progression of post-traumatic distress following combat exposure may be related to sensitization to the effects of post-deployment stressors during the first year following return from deployment. © 2013 Springer-Verlag Berlin Heidelberg.


den Uyl T.E.,University of Amsterdam | Gladwin T.E.,University of Amsterdam | Gladwin T.E.,Research Center Military Mental Health | Wiers R.W.,University of Amsterdam
Alcoholism: Clinical and Experimental Research | Year: 2016

Background: Cognitive bias modification (CBM) can be used to retrain automatic approach tendencies for alcohol. We investigated whether changing cortical excitability with transcranial direct current stimulation (tDCS) could enhance CBM effects in hazardous drinkers. We also studied the underlying mechanisms by including behavioral (craving, implicit associations, approach tendencies) and electrophysiological (event-related potentials) measurements. Methods: The analytical sample consisted of 78 hazardous drinkers (Alcohol Use Disorders Identification Test >8) randomly assigned to 4 conditions in a 2-by-2 factorial design (control/active CBM and sham/active tDCS). The intervention consisted of 3 sessions of CBM, specifically alcohol approach bias retraining, combined with 15 minutes 1 mA tDCS over the left dorsolateral prefrontal cortex. There was a pre- and postassessment before and after the intervention that included experimental tasks (Approach Avoidance Task, Implicit Association Task) and an electroencephalogram with an oddball and cue-reactivity task. Results: tDCS decreased cue-induced craving (but not overall craving) on postassessment. CBM did not induce an avoidance bias during assessment. During the training, active and control-CBM only differed in bias score during the first session. We found no enhancement effects of tDCS on CBM. Electrophysiological data showed no clear effects of active tDCS or CBM on the P300. Conclusions: There were no electrophysiological or behavioral effects of repeated CBM and/or tDCS, except for an effect of tDCS on craving. Applied in these specific ways these techniques appear to have limited effects in a hazardous drinking population. Copyright © 2016 by the Research Society on Alcoholism


Smid G.E.,Foundation Centrum 45 Arq | van Zuiden M.,University of Amsterdam | Geuze E.,Research Center Military Mental Health | Geuze E.,University Utrecht | And 6 more authors.
Psychoneuroendocrinology | Year: 2015

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. © 2014 Elsevier Ltd.


van Zuiden M.,University Utrecht | van Zuiden M.,Research Center Military Mental Health | Heijnen C.J.,University Utrecht | van de Schoot R.,University Utrecht | And 7 more authors.
PLoS ONE | Year: 2011

Major depressive disorder (MDD) is frequently diagnosed in military personnel returning from deployment. Literature suggests that MDD is associated with a pro-inflammatory state. To the best of our knowledge, no prospective, longitudinal studies on the association between development of depressive symptomatology and cytokine production by peripheral blood leukocytes have been published. The aim of this study was to investigate whether the presence of depressive symptomatology six months after military deployment is associated with the capacity to produce cytokines, as assessed before and after deployment. 1023 military personnel were included before deployment. Depressive symptoms and LPS- and T-cell mitogen-induced production of 16 cytokines and chemokines in whole blood cultures were measured before (T0), 1 (T1), and 6 (T2) months after return from deployment. Exploratory structural equation modeling (ESEM) was used for data reduction into cytokine patterns. Multiple group latent growth modeling was used to investigate differences in the longitudinal course of cytokine production between individuals with (n = 68) and without (n = 665) depressive symptoms at T2. Individuals with depressive symptoms after deployment showed higher T-cell cytokine production before deployment. Moreover, pre-deployment T-cell cytokine production significantly predicted the presence of depressive symptomatology 6 months after return. There was an increase in T-cell cytokine production over time, but this increase was significantly smaller in individuals developing depressive symptoms. T-cell chemokine and LPS-induced innate cytokine production decreased over time and were not associated with depressive symptoms. These results indicate that increased T-cell mitogen-induced cytokine production before deployment may be a vulnerability factor for development of depressive symptomatology in response to deployment to a combat-zone. In addition, deployment to a combat-zone affects the capacity of T-cells and monocytes to produce cytokines and chemokines until at least 6 months after return. © 2011 van Zuiden et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Reijnen A.,Research Center Military Mental Health | Reijnen A.,University Utrecht | Reijnen A.,Leiden University | Rademaker A.R.,Research Center Military Mental Health | And 6 more authors.
European Psychiatry | Year: 2015

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 6. months and 1 and 2. years 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. © 2014 Elsevier Masson SAS.


van Zuiden M.,University Utrecht | van Zuiden M.,Research Center Military Mental Health | van Zuiden M.,University of Amsterdam | Heijnen C.J.,University Utrecht | And 7 more authors.
Psychoneuroendocrinology | Year: 2012

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-α 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-α 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. © 2012 Elsevier Ltd.


Den Uyl T.E.,University of Amsterdam | Gladwin T.E.,University of Amsterdam | Gladwin T.E.,Research Center Military Mental Health | Wiers R.W.,University of Amsterdam
Biological Psychology | Year: 2015

Previous research has shown that stimulation of the left dorsolateral prefrontal cortex (DLPFC) enhances working memory (e.g. in the n-back task), and reduces craving for cigarettes and alcohol. Stimulation of the right inferior frontal gyrus (IFG) improves response inhibition. The underlying mechanisms are not clearly understood, nor is it known whether IFG stimulation also reduces craving. Here, we compared effects of DLPFC, IFG, and sham stimulation on craving in heavy drinkers in a small sample (. n=. 41). We also tested effects of tDCS on overcoming response biases due to associations between alcohol and valence and alcohol and approach, using implicit association tests (IATs). Mild craving was reduced after DLPFC stimulation. Categorization of valence attribute words in the IAT was faster after DLPFC stimulation. We conclude that DLPFC stimulation can reduce craving in heavy drinkers, but found no evidence for tDCS induced changes in alcohol biases, although low power necessitates caution. © 2014 Elsevier B.V.


Reijnen A.,Leiden University | Rademaker A.R.,Research Center Military Mental Health | Vermetten E.,Leiden University | Geuze E.,University Utrecht
European Psychiatry | Year: 2014

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 6. months and 1 and 2. years 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. © 2014 Elsevier Masson SAS.


PubMed | Leiden University, University Utrecht and Research Center Military Mental Health
Type: Journal Article | Journal: European psychiatry : the journal of the Association of European Psychiatrists | Year: 2015

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.Military personnel (n=994) completed various questionnaires at 5 time-points; starting prior to deployment and following the same cohort at 1 and 6 months and 1 and 2 years after their return from Afghanistan.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.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.This project was funded by the Dutch Ministry of Defence.

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