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Background: Military missions, especially those involving combat exposure, are associated with an increased risk of depression. Understanding the long-term course of depressive symptoms post -deployment is important to improve decision -making regarding deployment and mental health policies in the military. This study investigates trajectories of depressive symptoms in the Dutch army, exploring the influence of factors such as demographics, early -life trauma, posttraumatic stress disorder (PTSD) symptoms, and deployment stressors. Methods: A cohort of 1032 military men and women deployed to Afghanistan (2005 - 2008) was studied from preto 10 years post -deployment. Depressive and PTSD symptoms were assessed using the Symptom CheckList-90 and the Self -Rating Inventory for PTSD. Demographics, early trauma, and deployment experiences were collected at baseline and after deployment, respectively. Latent Class Growth Analysis was used to explore heterogeneity in trajectories of depressive symptoms over time. Results: Four trajectories were found: resilient (65%), intermediate -stable (20%), symptomatic -chronic (9%), and late -onset -increasing (6%). The resilient group experienced fewer deployment stressors, while the symptomaticchronic group reported more early life traumas. Trajectories with elevated depressive symptoms consistently demonstrated higher PTSD symptoms. Limitations: Potential nonresponse bias and missing information due to the longitudinal design and extensive follow-up times. Conclusions: This study identified multiple trajectories of depressive symptoms in military personnel up to 10 years post -deployment, associated with early trauma, deployment stressors, adverse life events and PTSD symptoms. The prevalence of the resilient trajectory suggests a substantial level of resilience among deployed military personnel. These findings provide valuable insights and a foundation for further research.

This narrative state-of-the-art review paper describes the progress in the understanding and treatment of Posttraumatic Stress Disorder (PTSD). Over the last four decades, the scientific landscape has matured, with many interdisciplinary contributions to understanding its diagnosis, etiology, and epidemiology. Advances in genetics, neurobiology, stress pathophysiology, and brain imaging have made it apparent that chronic PTSD is a systemic disorder with high allostatic load. The current state of PTSD treatment includes a wide variety of pharmacological and psychotherapeutic approaches, of which many are evidence-based. However, the myriad challenges inherent in the disorder, such as individual and systemic barriers to good treatment outcome, comorbidity, emotional dysregulation, suicidality, dissociation, substance use, and trauma-related guilt and shame, often render treatment response suboptimal. These challenges are discussed as drivers for emerging novel treatment approaches, including early interventions in the Golden Hours, pharmacological and psychotherapeutic interventions, medication augmentation interventions, the use of psychedelics, as well as interventions targeting the brain and nervous system. All of this aims to improve symptom relief and clinical outcomes. Finally, a phase orientation to treatment is recognized as a tool to strategize treatment of the disorder, and position interventions in step with the progression of the pathophysiology. Revisions to guidelines and systems of care will be needed to incorporate innovative treatments as evidence emerges and they become mainstream. This generation is well-positioned to address the devastating and often chronic disabling impact of traumatic stress events through holistic, cutting-edge clinical efforts and interdisciplinary research.

Participating in scientific conferences and professional networking support productivity in research. However, there are barriers for early career scientists to benefit from these activities. In 2023, the International College of Neuropsychopharmacology (CINP) Committee for Early Careers organised the first edition of the CINP Research Fellowship for Early Careers to support international collaboration of junior neuroscientists and facilitate in-person exchange between early career and senior investigators. The programme included online and in-person sessions, the latter during the 34th CINP World Congress in Montreal. Selected fellows had the opportunity to learn and make round-table discussions with renowned scientists, including Professors Paola Dazzan, Alan Frazer, Gabriella Gobbi, Anthony Grace, Oliver Howes, Kazutaka Ikeda, Kazuyuki Nakagome, Maria Oquendo, Dan Rujescu, Eric Vermetten, and Joseph Zohar, enabling early career researchers to understand each mentor’s main scientific trajectory and research methodology. The underpinning aim to support the global networking of early career researchers was achieved through the programme, as evidenced by the ensuing collaborative projects.

Item does not contain fulltext, Background: The International Trauma Questionnaire (ITQ) is a recent self-report measure to assess the severity and probable posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) as defined by the 11th revision of the International Classification of Diseases. Few studies have examined the psychometric properties of full and short ITQ versions in depth. Therefore, we aimed to evaluate the psychometric properties of the Dutch-translated 28-item ITQ and the 12-item version. Method: Data were used from existing clinical studies and routine clinical assessments for the 28-item (n = 956) and 12-item (N = 4,944) ITQ versions in trauma-exposed treatment-seeking individuals in the Netherlands. Internal consistency and factor validity were assessed, and rates of probable PTSD and CPTSD were estimated. In addition, convergent and discriminant validity were examined by correlations with similar and dissimilar measures. Results: Both versions of the ITQ showed good internal consistency and convergent validity. Confirmatory factor analysis showed that both a first-order correlated six-factor model and a two-factor second-order model were a good representation of the latent structure for the ITQ-12. The ITQ-12 resulted in higher CPTSD rates compared to the ITQ-28 (47% vs. 36.3%), while a similar number of patients met the criteria for either PTSD or CPTSD (70.6% vs. 76.4%). Conclusion: Internal consistency and convergent validity for the ITQ-12 and ITQ-28 were supported. The factorial validity was good for the ITQ-12 and acceptable for the ITQ-28. The discrepancy in CPTSD rates between the ITQ-12 and ITQ-28 calls for further testing of scoring methods against diagnostic clinical interviews for CPTSD., 02 november 2023, 10 p.

BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. RESULTS: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. CONCLUSIONS: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.

In order to decrease the risk of developing stress-related disorders after military deployment, biological vulnerability factors should be identified. Neuropeptide Y (NPY) is a peptide neurotransmitter that is associated with modulation of the stress response. Using the data of two longitudinal prospective cohort studies (N = 892 and N = 2427), plasma NPY (pNPY) was assessed as a possible susceptibility biomarker for the development of PTSD symptoms over time. Data collection started prior to deployment and follow-up assessments were completed up to two years after deployment. In pNPY levels, measured before and shortly after deployment, three distinct trajectories were identified. In both cohorts, these trajectories were not related to the level of reported PTSD symptoms over time and neither were pre-deployment pNPY levels. Whereas previous research suggested that high NPY levels might be a marker for resilience, the current findings suggest limited usefulness of peripherally measured NPY in the development of PTSD. © 2018 Elsevier B.V. Chemicals/CAS: neuropeptide Y, 82785-45-3, 83589-17-7

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.

Use of ED medication can be seen as a marker for ED. ED is associated with increasing age, exposure to traumatic events and physical injuries in military veterans. The objective of this study was to assess the prevalence of use of ED medication in Dutch military personnel in the period 2003–2012 and to assess its association with age and psychotropic medication use. Data on dispensing of ED medication, age and co-medication with psychotropic medication of all Dutch military personnel between 2003 and 2012 were collected. The prevalence of ED medication use in each year was estimated, stratified for age and use of psychotropic medication. The number of ED medication users increased a hundredfold from 0.09 to 9.29 per 1000 per year between 2003 and 2012. ED medication was more often used by men over 40 than under 40 (prevalence in 2012: 2.4% vs 0.2%, OR (2003–2012, adjusted for calendar year) 15.6, 95% CI 13.5–17.9) and by men using psychotropic medication (prevalence in 2012: 3.8% vs 0.9%, OR (2003–2012, adjusted for calendar year) 3.13, 95% CI 2.66–3.67). This study shows a strong increase between 2003 and 2012 in a number of ED medication users in male Dutch military personnel. ED medication use increases with age and with psychotropic medication use.International Journal of Impotence Research advance online publication, 17 November 2016; doi:10.1038/ijir.2016.44.

Item does not contain fulltext, Consistent failure over the past few decades to reduce the high prevalence of stress-related disorders has motivated a search for alternative research strategies. Resilience refers to the phenomenon of many people maintaining mental health despite exposure to psychological or physical adversity. Instead of aiming to understand the pathophysiology of stress-related disorders, resilience research focuses on protective mechanisms that shield people against the development of such disorders and tries to exploit its insights to improve treatment and, in particular, disease prevention. To fully harness the potential of resilience research, a critical appraisal of the current state of the art - in terms of basic concepts and key methods - is needed. We highlight challenges to resilience research and make concrete conceptual and methodological proposals to improve resilience research. Most importantly, we propose to focus research on the dynamic processes of successful adaptation to stressors in prospective longitudinal studies.

Item does not contain fulltext, Consistent failure over the past few decades to reduce the high prevalence of stress-related disorders has motivated a search for alternative research strategies. Resilience refers to the phenomenon of many people maintaining mental health despite exposure to psychological or physical adversity. Instead of aiming to understand the pathophysiology of stress-related disorders, resilience research focuses on protective mechanisms that shield people against the development of such disorders and tries to exploit its insights to improve treatment and, in particular, disease prevention. To fully harness the potential of resilience research, a critical appraisal of the current state of the art - in terms of basic concepts and key methods - is needed. We highlight challenges to resilience research and make concrete conceptual and methodological proposals to improve resilience research. Most importantly, we propose to focus research on the dynamic processes of successful adaptation to stressors in prospective longitudinal studies.

Item does not contain fulltext, OBJECTIVE: The purpose of this study was to examine course and predictors of fatigue in military personnel deployed to Afghanistan. METHODS: A total of 906 soldiers in the Dutch Armed Forces who participated in a 4-month mission to Afghanistan were included in this study. Assessment took place prior to and 1, 6, 12, and 24 months after deployment. Data were collected between 2005 and 2011. The fatigue severity subscale of the Checklist Individual Strength was used to indicate the level of fatigue during the previous 2 weeks. Mixed models and logistic regression analysis were used to predict course and prevalence of fatigue after deployment. Predictors of postdeployment fatigue were assessed prior to deployment. RESULTS: The mean level of fatigue increased significantly following deployment (B = 0.58, P = .007). In total, 274 soldiers (30.2%) were severely fatigued at least once after deployment and 130 (14.3%) soldiers had recurrent levels of severe fatigue. Only a minority of the veterans with severe fatigue could be classified as having posttraumatic stress disorder (PTSD, per DSM-IV-TR criteria) or potential medical problems. Significant predeployment predictors of less favorable courses of fatigue after deployment were higher levels of fatigue (B = 0.46, P

Item does not contain fulltext, OBJECTIVE: The purpose of this study was to examine course and predictors of fatigue in military personnel deployed to Afghanistan. METHODS: A total of 906 soldiers in the Dutch Armed Forces who participated in a 4-month mission to Afghanistan were included in this study. Assessment took place prior to and 1, 6, 12, and 24 months after deployment. Data were collected between 2005 and 2011. The fatigue severity subscale of the Checklist Individual Strength was used to indicate the level of fatigue during the previous 2 weeks. Mixed models and logistic regression analysis were used to predict course and prevalence of fatigue after deployment. Predictors of postdeployment fatigue were assessed prior to deployment. RESULTS: The mean level of fatigue increased significantly following deployment (B = 0.58, P = .007). In total, 274 soldiers (30.2%) were severely fatigued at least once after deployment and 130 (14.3%) soldiers had recurrent levels of severe fatigue. Only a minority of the veterans with severe fatigue could be classified as having posttraumatic stress disorder (PTSD, per DSM-IV-TR criteria) or potential medical problems. Significant predeployment predictors of less favorable courses of fatigue after deployment were higher levels of fatigue (B = 0.46, P

Item does not contain fulltext, 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.

Item does not contain fulltext, 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.

Item does not contain fulltext, 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.

The aim of this study was to investigate the relationship between the experience of a moral dilemma, well-being and self-transcendence. The confrontation with a mayor life event, such as a moral dilemma, can alter the previous beliefs and assumptions of an individual about the world and about the self. Self-transcendence can potentially help individuals to cope when they are confronted with a moral dilemma because it is assumed that it supports the formation of new assumptions. Sixty-two participants (military personnel) filled out a questionnaire to determine their level of self-transcendence, well-being and level of psychopathological symptoms. They also participated in a semi-structured interview to determine whether they have had experienced a moral dilemma. Contrary to expectations no clear relations were found between experiencing a moral dilemma, well-being and self-transcendence. In regards to well-being and self-transcendence only certain aspects (welfare and intuitiveness) were related, but in another direction than hypothesized. Intuitiveness was related to a low level of well-being. The expected moderation effect of self-transcendence could not be conducted due to statistical shortcomings. Because participants scored lower on self-transcendence and on psychopathological symptoms compared to the normal population it is possible that military personnel is very down to earth and do not need self-transcendence as a coping mechanism. But this could not be determined in this study and could provide clues for further research.

The aim of this study was to investigate the relationship between the experience of a moral dilemma, well-being and self-transcendence. The confrontation with a mayor life event, such as a moral dilemma, can alter the previous beliefs and assumptions of an individual about the world and about the self. Self-transcendence can potentially help individuals to cope when they are confronted with a moral dilemma because it is assumed that it supports the formation of new assumptions. Sixty-two participants (military personnel) filled out a questionnaire to determine their level of self-transcendence, well-being and level of psychopathological symptoms. They also participated in a semi-structured interview to determine whether they have had experienced a moral dilemma. Contrary to expectations no clear relations were found between experiencing a moral dilemma, well-being and self-transcendence. In regards to well-being and self-transcendence only certain aspects (welfare and intuitiveness) were related, but in another direction than hypothesized. Intuitiveness was related to a low level of well-being. The expected moderation effect of self-transcendence could not be conducted due to statistical shortcomings. Because participants scored lower on self-transcendence and on psychopathological symptoms compared to the normal population it is possible that military personnel is very down to earth and do not need self-transcendence as a coping mechanism. But this could not be determined in this study and could provide clues for further research.

Contains fulltext : 108044.pdf (publisher's version ) (Open Access), 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.