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Post-Traumatic Stress Disorders: HELP
Articles by David M. Benedek
Based on 24 articles published since 2010
(Why 24 articles?)
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Between 2010 and 2020, D. Benedek wrote the following 24 articles about Stress Disorders, Post-Traumatic.
 
+ Citations + Abstracts
1 Review Severity and Symptom Trajectory in Combat-Related PTSD: a Review of the Literature. 2019

Able, Michael L / Benedek, David M. ·F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. Michael.able@usuhs.edu. · , North Bethesda, USA. Michael.able@usuhs.edu. · F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. ·Curr Psychiatry Rep · Pubmed #31172321.

ABSTRACT: PURPOSE OF REVIEW: Combat-related posttraumatic stress disorder is increasingly recognized as having a variable course in returning veterans. Relatively few studies have identified predictors of illness duration or severity in this population. This review sought to synthesize the existing literature. RECENT FINDINGS: The existing literature remains limited and heterogeneous. However, several studies identified hyperarousal and pre-deployment dissociation as predictive of disease severity, and re-experiencing as predictive of suicidality in veterans with combat-related PTSD. No other pre-, peri-, or posttraumatic psychosocial predictors of individual symptoms or overall disease severity have been identified in replicated studies. Important clinical factors to explore in the assessment of PTSD in combat veterans may now include hyperarousal and a history of dissociation as these may predict disease severity, and re-experiencing as this has been identified as a significant predictor of suicidality. Further study into this topic may reveal biological or more sensitive psychosocial markers predicting illness severity and prognosis.

2 Review VA's National PTSD Brain Bank: a National Resource for Research. 2017

Friedman, Matthew J / Huber, Bertrand R / Brady, Christopher B / Ursano, Robert J / Benedek, David M / Kowall, Neil W / McKee, Ann C / Anonymous1690917. ·National Center for PTSD, VA Medical Center, U.S. Department of Veterans Affairs, 215 North Main Street, White River Junction, VT, 05009, USA. Matthew.J.Friedman@Dartmouth.edu. · Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. Matthew.J.Friedman@Dartmouth.edu. · VA Boston Healthcare System, Boston University School of Medicine, 150 South Huntington Avenue, Building 1, Room 12C6, Boston, MA, 02130, USA. · Departments of Neurology, Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA. · VA Boston Healthcare System (151C), 150 South Huntington Avenue, Boston, MA, 02130, USA. · Center for the Study of Traumatic Stress (CSTS), Department of Psychiatry, Uniformed Services University of the Health Sciences, School of Medicine, 4301 Jones Bridge Rd, Bethesda, MD, 20814, USA. ·Curr Psychiatry Rep · Pubmed #28840457.

ABSTRACT: The National PTSD Brain Bank (NPBB) is a brain tissue biorepository established to support research on the causes, progression, and treatment of PTSD. It is a six-part consortium led by VA's National Center for PTSD with participating sites at VA medical centers in Boston, MA; Durham, NC; Miami, FL; West Haven, CT; and White River Junction, VT along with the Uniformed Services University of Health Sciences. It is also well integrated with VA's Boston-based brain banks that focus on Alzheimer's disease, ALS, chronic traumatic encephalopathy, and other neurological disorders. This article describes the organization and operations of NPBB with specific attention to: tissue acquisition, tissue processing, diagnostic assessment, maintenance of a confidential data biorepository, adherence to ethical standards, governance, accomplishments to date, and future challenges. Established in 2014, NPBB has already acquired and distributed brain tissue to support research on how PTSD affects brain structure and function.

3 Review Posttraumatic stress disorder from Vietnam to today: the evolution of understanding during Eugene Brody's tenure at the journal of nervous and mental disease. 2011

Benedek, David M. ·Department of Psychiatry and Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD 20814, USA. dbenedek@usuhs.mil ·J Nerv Ment Dis · Pubmed #21814076.

ABSTRACT: The psychological and behavioral consequences of exposure to traumatic events have been described throughout our history. However, the term posttraumatic stress disorder (PTSD) was not formally introduced into the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, until after Dr Eugene Brody--whose broad interests included refugee populations and victims of trauma--had already served as editor-in-chief of the Journal of Nervous and Mental Disease (JNMD) for 15 years. Advances in molecular biology, genetics, and imaging that occurred during Brody's tenure at the JNMD contributed significantly to our current understanding of the human fear response and the neurobiology of PTSD. Comprehensive treatment guidelines summarizing evidence-based treatment were published during his tenure, and the most recent American Psychiatric Association update to practice standards was published in the year before his passing. Thus, this review of the history and present state of the science of PTSD summarizes the lessons learned while Dr Brody dedicated his life to teaching us.

4 Review Posttraumatic stress disorder and traumatic stress: from bench to bedside, from war to disaster. 2010

Ursano, Robert J / Goldenberg, Matthew / Zhang, Lei / Carlton, Janis / Fullerton, Carol S / Li, He / Johnson, Luke / Benedek, David. ·Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University School of Medicine, Bethesda, Maryland 20814, USA. rursano@usuhs.mil ·Ann N Y Acad Sci · Pubmed #20955328.

ABSTRACT: War is a tragic event and its mental health consequences can be profound. Recent studies indicate substantial rates of posttraumatic stress disorder and other behavioral alterations because of war exposure. Understanding the psychological, behavioral, and neurobiological mechanism of mental health and behavioral changes related to war exposure is critical to helping those in need of care. Substantial work to encourage bench to bedside to community knowledge and communication is a core component of addressing this world health need.

5 Article Genetic association of FKBP5 with PTSD in US service members deployed to Iraq and Afghanistan. 2020

Zhang, Lei / Hu, Xian-Zhang / Yu, Tianzheng / Chen, Ze / Dohl, Jacob / Li, Xiaoxia / Benedek, David M / Fullerton, Carol S / Wynn, Gary / Barrett, James E / Li, Mian / Russell, Dale W / Anonymous2771079 / Ursano, Robert J. ·Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. Electronic address: Lezhang@USUHS.edu. · Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. · Consortium for Health and Military Performance, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. · Department of Neurology, Drexel University College of Medicine Philadelphia, PA, 19102-1192, USA. · Department of Neurology, Washington DC VA Medical Center, Washington, DC, 20422, USA. · Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA; Consortium for Health and Military Performance, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. ·J Psychiatr Res · Pubmed #31927265.

ABSTRACT: Post-traumatic stress disorder (PTSD) is a debilitating mental disorder with a prevalence of more than 7% in the US population and 12% in the military. An interaction of childhood trauma with FKBP5 (a glucocorticoid-regulated immunophilin) has been reported to be associated with PTSD in the general population. However, there are few reports on the association of FKBP5 with PTSD, particularly in important high-risk population such as the military. Here, we examined the association between four single-nucleotide polymorphisms (SNPs; rs3800373, rs9296158, rs1360780, rs9470080) covering the FKBP5 gene and probable PTSD in US service members deployed to Iraq and Afghanistan, a high-risk military population (n = 3890) (Hines et al., 2014). We found that probable PTSD subjects were significantly more likely to carry the A-allele of rs3800373, G-allele of rs9296158, C-allele of rs1360780, and C-allele of rs9470080. Furthermore, the four SNPs were in one block of strong pairwise linkage disequilibrium (r = 0.91-0.96). Within the block there were two major haplotypes of CATT and AGCC (rs3800373-rs9296158-rs1360780-rs9470080) that account for 99% of haplotype diversity. The distribution of the AGCC haplotype was significantly higher in probable PTSD subjects compared to non-PTSD (p<.05). The diplotype-based analysis indicated that the AGCC carriers tended to be probable PTSD. In this study, we demonstrated the association between FKBP5 and probable PTSD in US service members deployed to Iraq and Afghanistan, indicating that FKBP5 might be a risk factor for PTSD.

6 Article Association between leukocyte telomere length and hostility in US army service members. 2019

Zhang, Lei / Hu, Xian-Zhang / Russell, Dale W / Benedek, David M / Fullerton, Carol S / Naifeh, James A / Li, Xiaoxia / Chen, Ze / Wu, Hongyan / Ng, Tsz Hin H / Aliaga, Pablo / Kao, Tzu-Cheg / Yu, Tianzheng / Dohl, Jacob / Wynn, Gary / Ursano, Robert J. ·Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA. Electronic address: lezhang@usuhs.edu. · Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA. · Department of Preventive Medicine & Biostatistics, USUHS, USA. · Consortium for Health and Military Performance, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. ·Neurosci Lett · Pubmed #31039427.

ABSTRACT: Hostility is a common form of emotionally charged anger which can lead to maladaptive and unhealthy behaviors. Significant association between shortened telomeres and greater levels of hostility has been observed in civilian populations, but has not yet been comprehensively studied in military populations. Our study investigates the relationship between hostility, post-traumatic stress disorder (PTSD), and leukocyte telomere length (LTL) in a sample of United States Army Special Operations personnel (n = 474) who deployed to Iraq and/or Afghanistan as part of combat operations. Hostility was measured with five items from the Brief Symptom Inventory (BSI). PTSD was determined using the PTSD Checklist (PCL) total score. The LTL was assessed using quantitative polymerase chain reaction methods and regression analyses were conducted to determine the association of hostility and telomere length. PTSD subjects reported higher hostility scores compared with those without PTSD. Among the participants with PTSD, those with medium or high level of hostility had shorter LTL than those with low level hostility (P < 0.01). Stepwise regression indicated that hostility level and age, but not gender and PTSD, were negatively correlated with LTL. Univariate regression showed that total hostility score was negatively associated with LTL (CI= -0.06 to -0.002, Beta= -0.095, p < 0.039) as well as a significant correlation between LTL and hostility impulses (HI) (CI= -0.108 to -0.009, Beta= -0.106, p < 0.021) and hostility controlling (HC) (CI= -0.071 to -0.002, Beta= -0.095, p < 0.004). Multiple regression analyses revealed that, while HC has no significant association with LTL, HI was still negatively correlated with LTL (p = 0.021). Our data indicates that LTL is associated with HI levels. Prevention and treatment efforts designed to reduce hostility may help mitigate risk for LTL shortening, a process of cellular aging, and thus slow accelerated aged-related health outcomes.

7 Article Genetic predictor of current suicidal ideation in US service members deployed to Iraq and Afghanistan. 2019

Zhang, Lei / Hu, Xian-Zhang / Benedek, David M / Fullerton, Carol S / Forsten, Robert D / Naifeh, James A / Li, Xiaoxia / Anonymous1221024. ·Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, USA. Electronic address: lezhang@usuhs.mil. · Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, USA. ·J Psychiatr Res · Pubmed #30904785.

ABSTRACT: OBJECTIVE: Suicide is one of the ten leading causes of death in United States and the suicide rate in the military population has increased since the start of the Iraq and Afghanistan wars. However, few biomarkers for current suicidal ideation (CSI) have been identified. The current study examined the association of four candidate genes with CSI in active duty US Army Special Operations Command and National Guard units (n = 3,889) who served in Iraq and Afghanistan between November 2009 and July 2014. METHODS: Current PTSD symptoms and CSI were assessed using the PTSD Checklist (PCL) and PHQ-9, respectively. Traumatic events were assessed using items from the Life Events Checklist (LEC) that met the DSM-IV PTSD criteria of a traumatic stressor. All genotypes of saliva DNA were discriminated using the TaqMan 5'-exonuclease assay. RESULTS: The associations between CSI and brain-derived neurotrophic factor (BDNF), FK506 binding protein (FKBP5), catechol-O-methyltransferase (COMT), or S100A10 (p11) were examined. We found CSI was associated with BDNF (OR = 1.5, 95% CI = 1.5-1.8, P = 0.0002), but not FKBP5, COMT and p11. Female soldiers reported CSI more often than males (χ2 = 7.403, p = 0.0065), although gender did not affect CSI severity. In addition, associations were found between CSI and depression, PTSD, and BDNF, but not traumatic events. The BDNF Val66Met contributed to the severity of CSI even after adjusting to PTSD, depression and LEC. CONCLUSIONS: The associations of BDNF with CSI and its severity suggest that BDNF may be a predictor of suicidal risk and present an opportunity to develop laboratory tools with clinical implications in suicide prevention and treatment.

8 Article Homecoming-The Podcast. 2017

Benedek, David M / Wynn, Gary H / Ursano, Robert J. ·Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland. ·JAMA · Pubmed #28399229.

ABSTRACT: -- No abstract --

9 Article PTSD symptom severity and sensitivity to blood, injury, and mutilation in U.S. army special operations soldiers. 2017

Naifeh, James A / Ursano, Robert J / Benfer, Natasha / Wu, Hongyan / Herman, Michelle / Benedek, David M / Russell, Dale W / Benevides, K Nikki / Kao, Tzu-Cheg / Ng, Tsz Hin H / Aliaga, Pablo A / Wynn, Gary H / Zhang, Lei / Forsten, Robert D / Fullerton, Carol S. ·Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. · Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Electronic address: robert.ursano@usuhs.edu. · Division of Epidemiology and Biostatistics, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. · United States Army War College, Carlisle, PA, USA. ·Psychiatry Res · Pubmed #28142070.

ABSTRACT: Sensitivity to blood, injury, and mutilation (SBIM) may increase risk for posttraumatic stress disorder (PTSD), given that traumatic events often involve actual or perceived threat of bodily harm to oneself and/or others, including exposure to blood and other mutilation-related stimuli. A self-report questionnaire was administered to male, active duty, U.S. Army Special Operations Command soldiers who had deployed to Iraq and Afghanistan (n =694 males). We first used exploratory factor analysis to examine whether the 30-item Mutilation Questionnaire (Klorman et al., 1974) comprised a unitary measure of SBIM, finding that 10 of the items form a cohesive SBIM factor. Summed, those 10 SBIM items had a significant bivariate correlation with PTSD symptom severity. In a multiple regression analysis that included demographic characteristics and lifetime trauma exposure, SBIM was positively associated with PTSD symptom severity. Other significant multivariate predictors were high lifetime trauma exposure and junior enlisted rank. When trait neuroticism was added to the model to test the robustness of these findings, the association of SBIM with PTSD symptom severity remained significant. The results suggest that SBIM may be a risk factor for PTSD in male soldiers. Further research is warranted to improve measurement and understanding of SBIM.

10 Article Domestic Civil Support Missions Can Aggravate Negative Mental Health Outcomes Among National Guardsmen: The Moderating Role of Economic Difficulties. 2017

Russell, Dale W / Kazman, Josh B / Benedek, David M / Ursano, Robert J / Russell, Cristel A. ·F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. · Kogod School of Business, American University, Washington, DC, USA. ·J Trauma Stress · Pubmed #28141895.

ABSTRACT: Little research has addressed potentially negative health outcomes associated with domestic civil-oriented operations, but has focused instead on traditional military operations (e.g., combat). This study, conducted following a United States Defense Support to Civilian Authorities mission undertaken by National Guard forces (N = 330), showed that responding to such missions was linked to more negative mental health outcomes, including posttraumatic stress disorder (β = 0.23) and depression (β = 0.23), but only among those who reported difficulty meeting their basic socioeconomic needs and not among those who did not have difficulty meeting their basic needs. The study offers suggestions for identifying individuals who may be especially vulnerable to stressors.

11 Article PTSD: Towards a Patient-Level Understanding of a Complex Disorder. 2017

Wynn, Gary H / Benedek, David M. ·Department of Psychiatry, Uniformed Services University, Center for the Study of Traumatic Stress, Bethesda, MD. ·J Nerv Ment Dis · Pubmed #28129257.

ABSTRACT: -- No abstract --

12 Article Post-Traumatic Stress in Disaster First Responders. 2016

Morganstein, Joshua C / Benedek, David M / Ursano, Robert J. · ·Disaster Med Public Health Prep · Pubmed #27303761.

ABSTRACT: -- No abstract --

13 Article Mitochondria-focused gene expression profile reveals common pathways and CPT1B dysregulation in both rodent stress model and human subjects with PTSD. 2015

Zhang, L / Li, H / Hu, X / Benedek, D M / Fullerton, C S / Forsten, R D / Naifeh, J A / Li, X / Wu, H / Benevides, K N / Le, T / Smerin, S / Russell, D W / Ursano, R J. ·Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. · U.S. Army Pacific Command, Hawaiian Islands, HI, USA. ·Transl Psychiatry · Pubmed #26080315.

ABSTRACT: Posttraumatic stress disorder (PTSD), a trauma-related mental disorder, is associated with mitochondrial dysfunction in the brain. However, the biologic approach to identifying the mitochondria-focused genes underlying the pathogenesis of PTSD is still in its infancy. Previous research, using a human mitochondria-focused cDNA microarray (hMitChip3) found dysregulated mitochondria-focused genes present in postmortem brains of PTSD patients, indicating that those genes might be PTSD-related biomarkers. To further test this idea, this research examines profiles of mitochondria-focused gene expression in the stressed-rodent model (inescapable tail shock in rats), which shows characteristics of PTSD-like behaviors and also in the blood of subjects with PTSD. This study found that 34 mitochondria-focused genes being upregulated in stressed-rat amygdala. Ten common pathways, including fatty acid metabolism and peroxisome proliferator-activated receptors (PPAR) pathways were dysregulated in the amygdala of the stressed rats. Carnitine palmitoyltransferase 1B (CPT1B), an enzyme in the fatty acid metabolism and PPAR pathways, was significantly over-expressed in the amygdala (P < 0.007) and in the blood (P < 0.01) of stressed rats compared with non-stressed controls. In human subjects with (n = 28) or without PTSD (n = 31), significant over-expression of CPT1B in PTSD was also observed in the two common dysregulated pathways: fatty acid metabolism (P = 0.0027, false discovery rate (FDR) = 0.043) and PPAR (P = 0.006, FDR = 0.08). Quantitative real-time polymerase chain reaction validated the microarray findings and the CPT1B result. These findings indicate that blood can be used as a specimen in the search for PTSD biomarkers in fatty acid metabolism and PPAR pathways, and, in addition, that CPT1B may contribute to the pathology of PTSD.

14 Article Corticosterone mitigates the stress response in an animal model of PTSD. 2015

Jia, Min / Smerin, Stanley E / Zhang, Lei / Xing, Guoqiang / Li, Xiaoxia / Benedek, David / Ursano, Robert / Li, He. ·Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Service University of Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, MD 20814, USA. · Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Service University of Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, MD 20814, USA. Electronic address: he.li@usuhs.edu. ·J Psychiatr Res · Pubmed #25307716.

ABSTRACT: Activation of glucocorticoid receptor signaling in the stress response to traumatic events has been implicated in the pathogenesis of stress-associated psychiatric disorders such as post-traumatic stress disorder (PTSD). Elevated startle response and hyperarousal are hallmarks of PTSD, and are generally considered to evince fear (DSM V). To further examine the efficacy of corticosterone in treating hyperarousal and elevated fear, the present study utilized a learned helplessness stress model in which rats are restrained and subjected to tail shock for three days. These stressed rats develop a delayed long-lasting exaggeration of the acoustic startle response (ASR) and retarded body weight growth, similar to symptoms of PTSD patients (Myers et al., 2005; Speed et al., 1989). We demonstrate that both pre-stress and post-stress administration of corticosterone (3 mg/kg/day) mitigates a subsequent exaggeration of the ASR measured 14 days after cessation of the stress protocol. Furthermore, the mitigating efficacy of pre-stress administration of corticosterone (3 mg/kg/day for three days) appeared to last significantly longer, up to 21 days after the cessation of the stress protocol, in comparison to that of post-stress administration of corticosterone. However, pre-stress administration of corticosterone at 0.3 mg/kg/day for three days did not mitigate stress-induced exaggeration of the ASR measured at both 14 and 21 days after the cessation of the stress protocol. In addition, pre-stress administration of corticosterone (3 mg/kg/day for three days) mitigates the retardation of body weight growth otherwise resulting from the stress protocol. Congruently, co-administration of the corticosterone antagonist RU486 (40 mg/kg/day for three days) with corticosterone (3 mg/kg/day) prior to stress diminished the mitigating efficacy of the exogenous corticosterone on exaggerated ASR and stress-retarded body weight. The relative efficacy of pre versus post administration of corticosterone and high versus low dose of corticosterone on stress-induced exaggeration of innate fear response and stress-retarded body weight growth indicate that exogenous corticosterone administration within an appropriate time window and dosage are efficacious in diminishing traumatic stress induced pathophysiological processes. Clinical implications associated with the efficacy of prophylactic and therapeutic corticosterone therapy for mitigating symptoms of PTSD are discussed, particularly in relation to diminishing hyperarousal and exaggerated innate fear response.

15 Article Randomized effectiveness trial of a brief course of acupuncture for posttraumatic stress disorder. 2014

Engel, Charles C / Cordova, Elizabeth H / Benedek, David M / Liu, Xian / Gore, Kristie L / Goertz, Christine / Freed, Michael C / Crawford, Cindy / Jonas, Wayne B / Ursano, Robert J. ·*Deployment Health Clinical Center, Walter Reed National Military Medical Center †Center for the Study of Traumatic Stress (CSTS) ‡Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD §Palmer Center for Chiropractic Research, Davenport, IA ∥Samueli Institute, Alexandria, VA. ·Med Care · Pubmed #25397825.

ABSTRACT: BACKGROUND: Initial posttraumatic stress disorder (PTSD) care is often delayed and many with PTSD go untreated. Acupuncture appears to be a safe, potentially nonstigmatizing treatment that reduces symptoms of anxiety, depression, and chronic pain, but little is known about its effect on PTSD. METHODS: Fifty-five service members meeting research diagnostic criteria for PTSD were randomized to usual PTSD care (UPC) plus eight 60-minute sessions of acupuncture conducted twice weekly or to UPC alone. Outcomes were assessed at baseline and 4, 8, and 12 weeks postrandomization. The primary study outcomes were difference in PTSD symptom improvement on the PTSD Checklist (PCL) and the Clinician-administered PTSD Scale (CAPS) from baseline to 12-week follow-up between the 2 treatment groups. Secondary outcomes were depression, pain severity, and mental and physical health functioning. Mixed model regression and t test analyses were applied to the data. RESULTS: Mean improvement in PTSD severity was significantly greater among those receiving acupuncture than in those receiving UPC (PCLΔ=19.8±13.3 vs. 9.7±12.9, P<0.001; CAPSΔ=35.0±20.26 vs. 10.9±20.8, P<0.0001). Acupuncture was also associated with significantly greater improvements in depression, pain, and physical and mental health functioning. Pre-post effect-sizes for these outcomes were large and robust. CONCLUSIONS: Acupuncture was effective for reducing PTSD symptoms. Limitations included small sample size and inability to parse specific treatment mechanisms. Larger multisite trials with longer follow-up, comparisons to standard PTSD treatments, and assessments of treatment acceptability are needed. Acupuncture is a novel therapeutic option that may help to improve population reach of PTSD treatment.

16 Article Mitochondrial Gene Expression Profiles and Metabolic Pathways in the Amygdala Associated with Exaggerated Fear in an Animal Model of PTSD. 2014

Li, He / Li, Xin / Smerin, Stanley E / Zhang, Lei / Jia, Min / Xing, Guoqiang / Su, Yan A / Wen, Jillian / Benedek, David / Ursano, Robert. ·Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences , Bethesda, MD , USA. · Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center , Washington, DC , USA. · Department of Gene and Protein Biomarkers, GenProMarkers , Rockville, MD , USA. ·Front Neurol · Pubmed #25295026.

ABSTRACT: The metabolic mechanisms underlying the development of exaggerated fear in post-traumatic stress disorder (PTSD) are not well defined. In the present study, alteration in the expression of genes associated with mitochondrial function in the amygdala of an animal model of PTSD was determined. Amygdala tissue samples were excised from 10 non-stressed control rats and 10 stressed rats, 14 days post-stress treatment. Total RNA was isolated, cDNA was synthesized, and gene expression levels were determined using a cDNA microarray. During the development of the exaggerated fear associated with PTSD, 48 genes were found to be significantly upregulated and 37 were significantly downregulated in the amygdala complex based on stringent criteria (p < 0.01). Ingenuity pathway analysis revealed up- or downregulation in the amygdala complex of four signaling networks - one associated with inflammatory and apoptotic pathways, one with immune mediators and metabolism, one with transcriptional factors, and one with chromatin remodeling. Thus, informatics of a neuronal gene array allowed us to determine the expression profile of mitochondrial genes in the amygdala complex of an animal model of PTSD. The result is a further understanding of the metabolic and neuronal signaling mechanisms associated with delayed and exaggerated fear.

17 Article A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS) for suicidal inpatients. 2014

George, Mark S / Raman, Rema / Benedek, David M / Pelic, Christopher G / Grammer, Geoffrey G / Stokes, Karen T / Schmidt, Matthew / Spiegel, Chad / Dealmeida, Nancy / Beaver, Kathryn L / Borckardt, Jeffrey J / Sun, Xiaoying / Jain, Sonia / Stein, Murray B. ·Ralph H. Johnson VA Medical Center, Charleston, SC, USA; Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA. Electronic address: georgem@musc.edu. · Department of Psychiatry, University of California at San Diego (UCSD), USA. · Walter Reed National Military Medical Center, USA. · Ralph H. Johnson VA Medical Center, Charleston, SC, USA; Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA. ·Brain Stimul · Pubmed #24731434.

ABSTRACT: BACKGROUND: Suicide attempts and completed suicides are common, yet there are no proven acute medication or device treatments for treating a suicidal crisis. Repeated daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) for 4-6 weeks is a new FDA-approved treatment for acute depression. Some open-label rTMS studies have found rapid reductions in suicidality. DESIGN: This study tests whether a high dose of rTMS to suicidal inpatients is feasible and safe, and also whether this higher dosing might rapidly improve suicidal thinking. This prospective, 2-site, randomized, active sham-controlled (1:1 randomization) design incorporated 9 sessions of rTMS over 3 days as adjunctive to usual inpatient suicidality treatment. The setting was two inpatient military hospital wards (one VA, the other DOD). PATIENTS: Research staff screened approximately 377 inpatients, yielding 41 adults admitted for suicidal crisis. Because of the funding source, all patients also had either post-traumatic stress disorder, mild traumatic brain injury, or both. TMS METHODS: Repetitive TMS (rTMS) was delivered to the left prefrontal cortex with a figure-eight solid core coil at 120% motor threshold, 10 Hertz (Hz), 5 second (s) train duration, 10 s intertrain interval for 30 minutes (6000 pulses) 3 times daily for 3 days (total 9 sessions; 54,000 stimuli). Sham rTMS used a similar coil that contained a metal insert blocking the magnetic field and utilized electrodes on the scalp, which delivered a matched somatosensory sensation. MAIN OUTCOME MEASURE: Primary outcomes were the daily change in severity of suicidal thinking as measured by the Beck Scale of Suicidal Ideation (SSI) administered at baseline and then daily, as well as subjective visual analog scale measures before and after each TMS session. Mixed model repeated measures (MMRM) analysis was performed on modified intent to treat (mITT) and completer populations. RESULTS: This intense schedule of rTMS with suicidal inpatients was feasible and safe. Minimal side effects occurred, none differing by arm, and the 3-day retention rate was 88%. No one died of suicide within the 6 month followup. From the mITT analyses, SSI scores declined rapidly over the 3 days for both groups (sham change -15.3 points, active change -15.4 points), with a trend for more rapid decline on the first day with active rTMS (sham change -6.4 points, active -10.7 points, P = 0.12). This decline was more pronounced in the completers subgroup [sham change -5.9 (95% CI: -10.1, -1.7), active -13 points (95% CI: -18.7, -7.4); P = 0.054]. Subjective ratings of 'being bothered by thoughts of suicide' declined non-significantly more with active rTMS than with sham at the end of 9 sessions of treatment in the mITT analysis [sham change -31.9 (95% CI: -41.7, -22.0), active change -42.5 (95% CI: -53.8, -31.2); P = 0.17]. There was a significant decrease in the completers sample [sham change -24.9 (95% CI: -34.4, -15.3), active change -43.8 (95% CI: -57.2, -30.3); P = 0.028]. CONCLUSIONS: Delivering high doses of left prefrontal rTMS over three days (54,000 stimuli) to suicidal inpatients is possible and safe, with few side effects and no worsening of suicidal thinking. The suggestions of a rapid anti-suicide effect (day 1 SSI data, Visual Analogue Scale data over the 3 days) need to be tested for replication in a larger sample. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01212848, TMS for suicidal ideation.

18 Article Biomarkers in an animal model for revealing neural, hematologic, and behavioral correlates of PTSD. 2012

Jia, Min / Meng, Fei / Smerin, Stanley E / Xing, Guoqiang / Zhang, Lei / Su, David M / Benedek, David / Ursano, Robert / Su, Yan A / Li, He. ·Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD 20892, USA. ·J Vis Exp · Pubmed #23093202.

ABSTRACT: Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for objective diagnosis but also for the evaluation of therapeutic efficacy and resilience to trauma. Ongoing research is directed at identifying molecular biomarkers for PTSD, including traumatic stress induced proteins, transcriptomes, genomic variances and genetic modulators, using biologic samples from subjects' blood, saliva, urine, and postmortem brain tissues. However, the correlation of these biomarker molecules in peripheral or postmortem samples to altered brain functions associated with psychiatric symptoms in PTSD remains unresolved. Here, we present an animal model of PTSD in which both peripheral blood and central brain biomarkers, as well as behavioral phenotype, can be collected and measured, thus providing the needed correlation of the central biomarkers of PTSD, which are mechanistic and pathognomonic but cannot be collected from people, with the peripheral biomarkers and behavioral phenotypes, which can. Our animal model of PTSD employs restraint and tail shocks repeated for three continuous days - the inescapable tail-shock model (ITS) in rats. This ITS model mimics the pathophysiology of PTSD (17, 7, 4, 10). We and others have verified that the ITS model induces behavioral and neurobiological alterations similar to those found in PTSD subjects (17, 7, 10, 9). Specifically, these stressed rats exhibit (1) a delayed and exaggerated startle response appearing several days after stressor cessation, which given the compressed time scale of the rat's life compared to a humans, corresponds to the one to three months delay of symptoms in PTSD patients (DSM-IV-TR PTSD Criterian D/E (13)), (2) enhanced plasma corticosterone (CORT) for several days, indicating compromise of the hypothalamopituitary axis (HPA), and (3) retarded body weight gain after stressor cessation, indicating dysfunction of metabolic regulation. The experimental paradigms employed for this model are: (1) a learned helplessness paradigm in the rat assayed by measurement of acoustic startle response (ASR) and a charting of body mass; (2) microdissection of the rat brain into regions and nuclei; (3) enzyme-linked immunosorbent assay (ELISA) for blood levels of CORT; (4) a gene expression microarray plus related bioinformatics tools (18). This microarray, dubbed rMNChip, focuses on mitochondrial and mitochondria-related nuclear genes in the rat so as to specifically address the neuronal bioenergetics hypothesized to be involved in PTSD.

19 Article Trauma-informed care for primary care: the lessons of war. 2012

Ursano, Robert J / Benedek, David M / Engel, Charles C. ·Department of Psychiatry, Uniformed Services University School of Medicine, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Robert.Ursano@usuhs.edu ·Ann Intern Med · Pubmed #22964876.

ABSTRACT: -- No abstract --

20 Article Evaluating transdiagnostic treatment for distress and impairment in veterans: a multi-site randomized controlled trial of Acceptance and Commitment Therapy. 2012

Lang, Ariel J / Schnurr, Paula P / Jain, Sonia / Raman, Rema / Walser, Robyn / Bolton, Elisa / Chabot, Aimee / Benedek, David. ·University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States. ajlang@ucsd.edu ·Contemp Clin Trials · Pubmed #21920461.

ABSTRACT: Military personnel who engaged in the conflicts in Afghanistan and Iraq frequently present for mental health care because of the stresses of service and readjustment. Although excellent treatments are available to treat the typical presenting problems, there is a need for additional empirically supported treatment approaches for this population. Because these veterans have high levels of comorbidity, transdiagnostic treatment - treatment that applies to more than one diagnosis - may be an efficient approach for this group. Acceptance and Commitment Therapy (ACT) is one such approach that is well-known and has high face validity for veterans, but it has not been rigorously evaluated as a treatment for trauma-related mental health problems. Described herein is an ongoing multi-site randomized clinical trial of ACT as compared to a psychotherapy control. Challenges in designing an RCT to evaluate transdiagnostic treatment and in executing a multi-site psychotherapy trial are discussed.

21 Article Military and civilian disaster response and resilience: from gene to policy. 2010

Hamaoka, Derrick A / Kilgore, Jocelyn A / Carlton, Janis / Benedek, David M / Ursano, Robert J. ·Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. ·Mil Med · Pubmed #23634476.

ABSTRACT: Disasters, such as war, terrorism, and natural disasters, affect individuals, groups, and communities. Although the focus is often on post-traumatic stress disorder (PTSD), it is only one of many potential responses to traumatic experiences. Fostering community and individual resilience can help mitigate the effects of disaster. Research, education, and early intervention are integral tools to inform an effective response. The Center for the Study of Traumatic Stress (CSTS) at the Uniformed Services University of the Health Sciences ascribes to such a model in its approach. Recent studies confirm that appreciation of biology and its relation to trauma response are necessary to our understanding of trauma's effects on humans, including trauma-associated disorders, resiliency, and recovery.

22 Minor Implementation and clinical characteristics of a posttraumatic stress disorder brain collection. 2018

Mighdoll, Michelle I / Deep-Soboslay, Amy / Bharadwaj, Rahul A / Cotoia, John A / Benedek, David M / Hyde, Thomas M / Kleinman, Joel E. ·Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland. ·J Neurosci Res · Pubmed #28609565.

ABSTRACT: A postmortem human brain collection to study posttraumatic stress disorder (PTSD) is critical for uncovering the molecular mechanisms that contribute to this psychiatric disorder. We describe here the PTSD brain collection at the Lieber Institute for Brain Development in Baltimore, Maryland, consisting of postmortem brain donations acquired between 2012 and 2017. Thus far, 87 brains from individuals meeting DSM-5 criteria for PTSD were collected after consent was obtained from legal next-of-kin, and subsequently clinically characterized for molecular studies. PTSD brain donors had high rates of comorbid diagnoses, including depression (62.1%), substance abuse (74.7%), drug-related death (69.0%), and suicide completion (17.2%). PTSD cases were subdivided into two categories: combat-related PTSD (n = 24) and noncombat/domestic PTSD (n = 63). The major differences between the combat-related and domestic PTSD cohorts were sex, drug-related death, and the prevalence of bipolar disorder (BPD) comorbidity. The combat-related group was entirely male, with only one BPD subject (4.2%), and had significantly fewer drug-related deaths (45.8%) in contrast to the domestic group (31.8% male, 36.5% bipolar, and 77.8% drug-related deaths). Medical examiners' offices, particularly in areas with higher military populations, are an excellent source for PTSD brain donations of both combat-related and domestic PTSD.

23 Minor The interaction between stressful life events and leukocyte telomere length is associated with PTSD. 2014

Zhang, L / Hu, X-Z / Benedek, D M / Fullerton, C S / Forsten, R D / Naifeh, J A / Li, X / Li, H / Benevides, K N / Smerin, S / Le, T / Choi, K / Ursano, R J. ·Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. · United States Army Special Operations Command, Fort Bragg, NC, USA. ·Mol Psychiatry · Pubmed #24189343.

ABSTRACT: -- No abstract --

24 Minor PTSD risk is associated with BDNF Val66Met and BDNF overexpression. 2014

Zhang, L / Benedek, D M / Fullerton, C S / Forsten, R D / Naifeh, J A / Li, X X / Hu, X Z / Li, H / Jia, M / Xing, G Q / Benevides, K N / Ursano, R J. ·Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. · United States Army Special Operations Command, Fort Bragg, NC, USA. ·Mol Psychiatry · Pubmed #23319005.

ABSTRACT: -- No abstract --