Eric Vermetten is a clinical psychiatrist and employed as strategic advisor (COL) of research at the Military Mental Health Service with the Dutch Ministry of Defense and Arq National Psychotrauma Center. His clinical work involves working with uniformed officers with complex PTSD. He holds an endowed chair in Psychiatry at the Department Psychiatry at Leiden UMC and is Adjunct Professor at the Department Psychiatry of New York UMC. He is trained in the Netherlands as well as in the USA in psychiatry and neuroscience. His focus is on medical/biological as well as psychiatric aspects of complex psychotrauma in military as well as civilian populations. He has widely published papers, chapters and and edited several books on stress, trauma, complex PTSD and neuroscience. His focus is history and development of field of medical psychotraumatology and interested in so called 'disruptive' appraoches to therapy, that potentially hold promise to better understand, design, and improve pathways to cure, e.g. 3MDR as well as novel use of psychedelics. Phone: +31 71 5263448 Address: Dept Psychiatry Albinusdreef 2 2333 ZA Leiden The Netherlands
The purpose of this study was to examine course and predictors of fatigue in military personnel d... more The purpose of this study was to examine course and predictors of fatigue in military personnel deployed to Afghanistan. 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. 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 c...
Introduction Soldiers have a higher risk for developing psychiatric disorders that require treatm... more Introduction Soldiers have a higher risk for developing psychiatric disorders that require treatment; often with antidepressants. However, antidepressants as well as the psychiatric disorder, may influence military readiness in several ways. In the general population, early discontinuation of antidepressant treatment is often seen. It is yet unknown whether this occurs to a similar extent in soldiers. The objective of this study was to evaluate discontinuation of antidepressant use by Dutch soldiers in the first 12 months after start and determinants thereof. Materials and Methods Data were obtained from the military pharmacy. All Dutch soldiers who started using an antidepressant between 2000 and 2014 were included. Kaplan–Meier curves were constructed to estimate the discontinuation rate over time and the influence of each determinant on discontinuation rate was estimated using Cox regression. Results About 25.9% of de 2479 starters had discontinued their antidepressant use after ...
Recent studies examining the association between posttraumatic stress disorder (PTSD) and acceler... more Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results. We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186). Associations between demographic and cellular variables and accelerated DNA methylation age were also examined, as was the moderating influence of demographic variables. Meta-analysis of regression coefficients from contributing cohorts revealed that childhood trauma exposure (when measured with the Childhood Trauma Questionnaire) and lifetime PTSD severity evidenced significant, albeit small, meta-analytic associations with accelerated DNA methylation age (ps = 0.028 and 0.016, respectively). Se...
Current topics in behavioral neurosciences, Jan 21, 2017
Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop following exposu... more Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop following exposure to or witnessing of a (potentially) threatening event. A critical issue is to pinpoint the (neuro)biological mechanisms underlying the susceptibility to stress-related disorder such as PTSD, which develops in the minority of ~15% of individuals exposed to trauma. Over the last few years, a first wave of epigenetic studies has been performed in an attempt to identify the molecular underpinnings of the long-lasting behavioral and mental effects of trauma exposure. The potential roles of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) in moderating or mediating the impact of severe stress and trauma are increasingly gaining attention. To date, most studies focusing on the roles of miRNAs in PTSD have, however, been completed in animals, using cross-sectional study designs and focusing almost exclusively on subjects with susceptible phenotypes. Therefore, there is a strong need for ne...
Current topics in behavioral neurosciences, Jan 21, 2017
Recently, a dissociative subtype of post-traumatic stress disorder (PTSD) has been included in th... more Recently, a dissociative subtype of post-traumatic stress disorder (PTSD) has been included in the DSM-5. This review focuses on the clinical and neurobiological features that distinguish the dissociative subtype of PTSD from non-dissociative PTSD. Clinically, the dissociative subtype of PTSD is associated with high PTSD severity, predominance of derealization and depersonalization symptoms, a more significant history of early life trauma, and higher levels of comorbid psychiatric disorders. Furthermore, PTSD patients with dissociative symptoms exhibit different psychophysiological and neural responses to the recall of traumatic memories. While individuals with non-dissociative PTSD exhibit an increased heart rate, decreased activation of prefrontal regions, and increased activation of the amygdala in response to traumatic reminders, individuals with the dissociative subtype of PTSD show an opposite pattern. It has been proposed that dissociation is a regulatory strategy to restrain...
Applied psychophysiology and biofeedback, Jan 31, 2017
There is a growing interest in the application of psychophysiological signals in more applied set... more There is a growing interest in the application of psychophysiological signals in more applied settings. Unidirectional sensory motor rhythm-training (SMR) has demonstrated consistent effects on sleep. In this study the main aim was to analyze to what extent participants could gain voluntary control over sleep-related parameters and secondarily to assess possible influences of this training on sleep metrics. Bidirectional training of SMR as well as heart rate variability (HRV) was used to assess the feasibility of training these parameters as possible brain computer interfaces (BCI) signals, and assess effects normally associated with unidirectional SMR training such as the influence on objective and subjective sleep parameters. Participants (n = 26) received between 11 and 21 training sessions during 7 weeks in which they received feedback on their personalized threshold for either SMR or HRV activity, for both up- and down regulation. During a pre- and post-test a sleep log was kep...
Several studies have shown the relationship between symptoms of posttraumatic stress disorder (PT... more Several studies have shown the relationship between symptoms of posttraumatic stress disorder (PTSD), somatic symptoms, and the mediating effect of depression and anxiety. The following study was conducted to investigate the relationship between PTSD symptoms and somatic complaints through underlying symptoms of depression and anxiety. The participants of the study were 2,799 veterans who were examined after a 6-month deployment. They were assessed using the PTSD Checklist (PCL-5) and Patient Health Questionnaire (PHQ) for depression, anxiety, and somatic complaints. To check the indirect effect of PTSD on somatic complaints through depression and anxiety, mediation model 4 (parallel mediation) of the SPSS PROCESS macro was used. There was a significant total indirect effect of PTSD through depression and anxiety on somatic complaints, b = 0.14, 95% confidence interval (CI) [0.12, 0.16], from which an indirect effect of PTSD on somatic complaints through depression was b = 0.08, 95%...
In an attempt to decrease the risk of developing mental health problems after military deployment... more In an attempt to decrease the risk of developing mental health problems after military deployment, it is important to find biological markers to identify those at risk. Oxytocin (OT) and arginine vasopressin (AVP) are potential biomarkers for the development of posttraumatic stress disorder (PTSD) because they are involved in the regulation of stress and anxiety. Therefore, the aim was to examine whether plasma OT (pOT) and AVP (pAVP) levels before and after deployment are biomarkers for the development of posttraumatic stress symptoms over time in addition to other known risk factors. This study is part of a large prospective cohort study on candidate markers for stress-related mental health symptoms and resiliency after deployment to a combat zone; Prospective Research in Stress-related Military Operations (PRISMO; NÂ =Â 907). Data was collected prior to deployment and follow-ups were performed at 1 and 6 months, and 1, 2, and 5 years post-deployment. Blood samples were collected in the first three assessments. The levels of pOT and pAVP were not significantly related to the development of PTSD symptoms over time. The results confirm that age, the experience of early life trauma, combat-related stressors and the presence of depressive symptoms are predictive for the development of PTSD symptoms over time. These findings showed that peripherally measured OT and AVP currently do not qualify as useful susceptibility biomarkers for the development of PTSD symptoms over time in military men after combat.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2017
Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in st... more Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N = 1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive...
Current topics in behavioral neurosciences, Jan 25, 2017
Three and a half decades of research on posttraumatic stress disorder (PTSD) has produced substan... more Three and a half decades of research on posttraumatic stress disorder (PTSD) has produced substantial knowledge on the pathobiology of this frequent and debilitating disease. However, despite all research efforts, so far no drug that has specifically targeted PTSD core symptoms progressed to clinical use. Instead, although not overly efficient, serotonin re-uptake inhibitors continue to be considered the gold standard of PTSD pharmacotherapy. The psychotherapeutic treatment and symptom-oriented drug therapy options available for PTSD treatment today show some efficacy, although not in all PTSD patients, in particular not in a substantial percent of those suffering from the detrimental sequelae of repeated childhood trauma or in veterans with combat related PTSD. PTSD has this in common with other psychiatric disorders - in particular effective treatment for incapacitating conditions such as resistant major depression, chronic schizophrenia, and frequently relapsing obsessive-compuls...
The GABA system is pivotal for an adequate response to a stressful environment but has remained l... more The GABA system is pivotal for an adequate response to a stressful environment but has remained largely unexplored in this context. The present study investigated the relationship of prospectively measured plasma GABA levels with psychopathology symptoms in military deployed to Afghanistan at risk for developing psychopathology following trauma exposure during deployment, including posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Plasma GABA levels were measured in military personnel (N=731) one month prior to deployment (T0), and one (T1) and six months (T2) after deployment using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Mental health problems and depressive symptoms were measured with the Dutch revised Symptom Checklist (SCL-90) and PTSD symptoms with the Dutch Self-Rating Inventory for PTSD (SRIP). Six months after deployment increases in GABA concentrations were present in individuals who had developed men...
Data Revues 09249338 V26ss1 S0924933811738354, 2011
Although posttraumatic stress disorder (PTSD) is associated with chronic pain, preliminary eviden... more Although posttraumatic stress disorder (PTSD) is associated with chronic pain, preliminary evidence suggests reduced experimental pain sensitivity in this disorder. The questions addressed in the present study were whether pain perception would also be reduced in PTSD patients who are not suffering from chronic pain symptoms, and whether a reduction in pain sensitivity would also be present in combat veterans who did not develop PTSD. For this, we determined thermal detection and pain thresholds in 10 male combat-related PTSD patients, 10 combat control subjects (no PTSD) and 10 healthy controls without combat experience. All subjects were pain free. First, we measured thermal sensory thresholds with ramped heat and cold stimuli using the method of limits. Ramped thermal sensory stimulation revealed no deficits for the detection of (non-noxious) f2.1thermal stimuli between groups. In contrast, heat and cold pain thresholds in both combat groups (PTSD and combat controls) were significantly increased compared to healthy controls. However, these stimuli could not distinguish between the two groups due to ceiling effects. When using longer-lasting heat stimulation at different temperatures (30 s duration; method of fixed stimuli), we found significantly lower frequency of pain reports in PTSD patients compared with both combat and healthy controls, as well as significantly lower pain ratings. Our results suggest an association of PTSD with reduced pain sensitivity, which could be related to PTSD-related (neuro-)psychological alterations or to a pre-existing risk factor for the disorder.
The purpose of this study was to examine course and predictors of fatigue in military personnel d... more The purpose of this study was to examine course and predictors of fatigue in military personnel deployed to Afghanistan. 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. 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 c...
Introduction Soldiers have a higher risk for developing psychiatric disorders that require treatm... more Introduction Soldiers have a higher risk for developing psychiatric disorders that require treatment; often with antidepressants. However, antidepressants as well as the psychiatric disorder, may influence military readiness in several ways. In the general population, early discontinuation of antidepressant treatment is often seen. It is yet unknown whether this occurs to a similar extent in soldiers. The objective of this study was to evaluate discontinuation of antidepressant use by Dutch soldiers in the first 12 months after start and determinants thereof. Materials and Methods Data were obtained from the military pharmacy. All Dutch soldiers who started using an antidepressant between 2000 and 2014 were included. Kaplan–Meier curves were constructed to estimate the discontinuation rate over time and the influence of each determinant on discontinuation rate was estimated using Cox regression. Results About 25.9% of de 2479 starters had discontinued their antidepressant use after ...
Recent studies examining the association between posttraumatic stress disorder (PTSD) and acceler... more Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results. We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186). Associations between demographic and cellular variables and accelerated DNA methylation age were also examined, as was the moderating influence of demographic variables. Meta-analysis of regression coefficients from contributing cohorts revealed that childhood trauma exposure (when measured with the Childhood Trauma Questionnaire) and lifetime PTSD severity evidenced significant, albeit small, meta-analytic associations with accelerated DNA methylation age (ps = 0.028 and 0.016, respectively). Se...
Current topics in behavioral neurosciences, Jan 21, 2017
Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop following exposu... more Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop following exposure to or witnessing of a (potentially) threatening event. A critical issue is to pinpoint the (neuro)biological mechanisms underlying the susceptibility to stress-related disorder such as PTSD, which develops in the minority of ~15% of individuals exposed to trauma. Over the last few years, a first wave of epigenetic studies has been performed in an attempt to identify the molecular underpinnings of the long-lasting behavioral and mental effects of trauma exposure. The potential roles of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) in moderating or mediating the impact of severe stress and trauma are increasingly gaining attention. To date, most studies focusing on the roles of miRNAs in PTSD have, however, been completed in animals, using cross-sectional study designs and focusing almost exclusively on subjects with susceptible phenotypes. Therefore, there is a strong need for ne...
Current topics in behavioral neurosciences, Jan 21, 2017
Recently, a dissociative subtype of post-traumatic stress disorder (PTSD) has been included in th... more Recently, a dissociative subtype of post-traumatic stress disorder (PTSD) has been included in the DSM-5. This review focuses on the clinical and neurobiological features that distinguish the dissociative subtype of PTSD from non-dissociative PTSD. Clinically, the dissociative subtype of PTSD is associated with high PTSD severity, predominance of derealization and depersonalization symptoms, a more significant history of early life trauma, and higher levels of comorbid psychiatric disorders. Furthermore, PTSD patients with dissociative symptoms exhibit different psychophysiological and neural responses to the recall of traumatic memories. While individuals with non-dissociative PTSD exhibit an increased heart rate, decreased activation of prefrontal regions, and increased activation of the amygdala in response to traumatic reminders, individuals with the dissociative subtype of PTSD show an opposite pattern. It has been proposed that dissociation is a regulatory strategy to restrain...
Applied psychophysiology and biofeedback, Jan 31, 2017
There is a growing interest in the application of psychophysiological signals in more applied set... more There is a growing interest in the application of psychophysiological signals in more applied settings. Unidirectional sensory motor rhythm-training (SMR) has demonstrated consistent effects on sleep. In this study the main aim was to analyze to what extent participants could gain voluntary control over sleep-related parameters and secondarily to assess possible influences of this training on sleep metrics. Bidirectional training of SMR as well as heart rate variability (HRV) was used to assess the feasibility of training these parameters as possible brain computer interfaces (BCI) signals, and assess effects normally associated with unidirectional SMR training such as the influence on objective and subjective sleep parameters. Participants (n = 26) received between 11 and 21 training sessions during 7 weeks in which they received feedback on their personalized threshold for either SMR or HRV activity, for both up- and down regulation. During a pre- and post-test a sleep log was kep...
Several studies have shown the relationship between symptoms of posttraumatic stress disorder (PT... more Several studies have shown the relationship between symptoms of posttraumatic stress disorder (PTSD), somatic symptoms, and the mediating effect of depression and anxiety. The following study was conducted to investigate the relationship between PTSD symptoms and somatic complaints through underlying symptoms of depression and anxiety. The participants of the study were 2,799 veterans who were examined after a 6-month deployment. They were assessed using the PTSD Checklist (PCL-5) and Patient Health Questionnaire (PHQ) for depression, anxiety, and somatic complaints. To check the indirect effect of PTSD on somatic complaints through depression and anxiety, mediation model 4 (parallel mediation) of the SPSS PROCESS macro was used. There was a significant total indirect effect of PTSD through depression and anxiety on somatic complaints, b = 0.14, 95% confidence interval (CI) [0.12, 0.16], from which an indirect effect of PTSD on somatic complaints through depression was b = 0.08, 95%...
In an attempt to decrease the risk of developing mental health problems after military deployment... more In an attempt to decrease the risk of developing mental health problems after military deployment, it is important to find biological markers to identify those at risk. Oxytocin (OT) and arginine vasopressin (AVP) are potential biomarkers for the development of posttraumatic stress disorder (PTSD) because they are involved in the regulation of stress and anxiety. Therefore, the aim was to examine whether plasma OT (pOT) and AVP (pAVP) levels before and after deployment are biomarkers for the development of posttraumatic stress symptoms over time in addition to other known risk factors. This study is part of a large prospective cohort study on candidate markers for stress-related mental health symptoms and resiliency after deployment to a combat zone; Prospective Research in Stress-related Military Operations (PRISMO; NÂ =Â 907). Data was collected prior to deployment and follow-ups were performed at 1 and 6 months, and 1, 2, and 5 years post-deployment. Blood samples were collected in the first three assessments. The levels of pOT and pAVP were not significantly related to the development of PTSD symptoms over time. The results confirm that age, the experience of early life trauma, combat-related stressors and the presence of depressive symptoms are predictive for the development of PTSD symptoms over time. These findings showed that peripherally measured OT and AVP currently do not qualify as useful susceptibility biomarkers for the development of PTSD symptoms over time in military men after combat.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2017
Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in st... more Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N = 1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive...
Current topics in behavioral neurosciences, Jan 25, 2017
Three and a half decades of research on posttraumatic stress disorder (PTSD) has produced substan... more Three and a half decades of research on posttraumatic stress disorder (PTSD) has produced substantial knowledge on the pathobiology of this frequent and debilitating disease. However, despite all research efforts, so far no drug that has specifically targeted PTSD core symptoms progressed to clinical use. Instead, although not overly efficient, serotonin re-uptake inhibitors continue to be considered the gold standard of PTSD pharmacotherapy. The psychotherapeutic treatment and symptom-oriented drug therapy options available for PTSD treatment today show some efficacy, although not in all PTSD patients, in particular not in a substantial percent of those suffering from the detrimental sequelae of repeated childhood trauma or in veterans with combat related PTSD. PTSD has this in common with other psychiatric disorders - in particular effective treatment for incapacitating conditions such as resistant major depression, chronic schizophrenia, and frequently relapsing obsessive-compuls...
The GABA system is pivotal for an adequate response to a stressful environment but has remained l... more The GABA system is pivotal for an adequate response to a stressful environment but has remained largely unexplored in this context. The present study investigated the relationship of prospectively measured plasma GABA levels with psychopathology symptoms in military deployed to Afghanistan at risk for developing psychopathology following trauma exposure during deployment, including posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Plasma GABA levels were measured in military personnel (N=731) one month prior to deployment (T0), and one (T1) and six months (T2) after deployment using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Mental health problems and depressive symptoms were measured with the Dutch revised Symptom Checklist (SCL-90) and PTSD symptoms with the Dutch Self-Rating Inventory for PTSD (SRIP). Six months after deployment increases in GABA concentrations were present in individuals who had developed men...
Data Revues 09249338 V26ss1 S0924933811738354, 2011
Although posttraumatic stress disorder (PTSD) is associated with chronic pain, preliminary eviden... more Although posttraumatic stress disorder (PTSD) is associated with chronic pain, preliminary evidence suggests reduced experimental pain sensitivity in this disorder. The questions addressed in the present study were whether pain perception would also be reduced in PTSD patients who are not suffering from chronic pain symptoms, and whether a reduction in pain sensitivity would also be present in combat veterans who did not develop PTSD. For this, we determined thermal detection and pain thresholds in 10 male combat-related PTSD patients, 10 combat control subjects (no PTSD) and 10 healthy controls without combat experience. All subjects were pain free. First, we measured thermal sensory thresholds with ramped heat and cold stimuli using the method of limits. Ramped thermal sensory stimulation revealed no deficits for the detection of (non-noxious) f2.1thermal stimuli between groups. In contrast, heat and cold pain thresholds in both combat groups (PTSD and combat controls) were significantly increased compared to healthy controls. However, these stimuli could not distinguish between the two groups due to ceiling effects. When using longer-lasting heat stimulation at different temperatures (30 s duration; method of fixed stimuli), we found significantly lower frequency of pain reports in PTSD patients compared with both combat and healthy controls, as well as significantly lower pain ratings. Our results suggest an association of PTSD with reduced pain sensitivity, which could be related to PTSD-related (neuro-)psychological alterations or to a pre-existing risk factor for the disorder.
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