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Robert J Ursano

Publications and source records attributed to Robert J Ursano.

At least 19 recordsLinked to original sources
PubMed2024

Blood-based DNA methylation and exposure risk scores predict PTSD with high accuracy in military and civilian cohorts.

BACKGROUND: Incorporating genomic data into risk prediction has become an increasingly popular approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. METHODS: Elastic Net was used to develop three risk score models using a discovery dataset (n&#x2009;=&#x2009;1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. RESULTS: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy&#x2009;=&#x2009;89%) using 3728 features and MoRSAE (accuracy&#x2009;=&#x2009;84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta&#x2009;=&#x2009;0.6839, p=0.006), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta&#x2009;=&#x2009;1.92; MoRS, beta&#x2009;=&#x2009;1.99 and MoRSAE, beta&#x2009;=&#x2009;1.77) displayed a significant (p&#x2009;<&#x2009;0.001) predictive power for post-deployment PTSD. CONCLUSION: The inclusion of exposure variables adds to the predictive power of MRS. Classification-based MRS may be useful in predicting risk of future PTSD in populations with anticipated trauma exposure. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting PTSD and, relatedly, improve their performance in independent cohorts.

Humans↗
PubMed2022

Epigenome-wide meta-analysis of PTSD symptom severity in three military cohorts implicates DNA methylation changes in genes involved in immune system and oxidative stress.

Epigenetic factors modify the effects of environmental factors on biological outcomes. Identification of epigenetic changes that associate with PTSD is therefore a crucial step in deciphering mechanisms of risk and resilience. In this study, our goal is to identify epigenetic signatures associated with PTSD symptom severity (PTSS) and changes in PTSS over time, using whole blood DNA methylation (DNAm) data (MethylationEPIC BeadChip) of military personnel prior to and following combat deployment. A total of 429 subjects (858 samples across 2 time points) from three male military cohorts were included in the analyses. We conducted two different meta-analyses to answer two different scientific questions: one to identify a DNAm profile of PTSS using a random effects model including both time points for each subject, and the other to identify a DNAm profile of change in PTSS conditioned on pre-deployment DNAm. Four CpGs near four genes (F2R, CNPY2, BAIAP2L1, and TBXAS1) and 88 differentially methylated regions (DMRs) were associated with PTSS. Change in PTSS after deployment was associated with 15 DMRs, of those 2 DMRs near OTUD5 and ELF4 were also associated with PTSS. Notably, three PTSS-associated CpGs near F2R, BAIAP2L1 and TBXAS1 also showed nominal evidence of association with change in PTSS. This study, which identifies PTSD-associated changes in genes involved in oxidative stress and immune system, provides novel evidence that epigenetic differences are associated with PTSS.

Adaptor Proteins, Signal Transducing↗
PubMed2020

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR.

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.

Basic Helix-Loop-Helix Proteins↗
PubMed2006

Stress and stressors of the early phases of the Persian Gulf War.

Soldiers who deployed to Saudi Arabia in support of Operation Desert Shield were exposed to a wide variety of stressors. These stressors from the pre-combat phase of the deployment undoubtedly affect the current health of Gulf War veterans, but the exact mechanisms and linkages are not known. This article examines the nature of those stressors and possible effects on later health of veterans.

Gulf War↗
PubMed2006

Stress-induced change of mitochondria membrane potential regulated by genomic and non-genomic GR signaling: a possible mechanism for hippocampus atrophy in PTSD.

Posttraumatic stress disorder (PTSD) is a common psychiatric disorder often accompanied by morphologic changes in the hippocampus. Brain imaging studies have demonstrated a strong relationship between PTSD and a reduction in the volume of the hippocampus; however, the mechanisms that cause such atrophy are not well understood. In an attempt to expand our knowledge of these mechanisms, our theory has focused on the role of mitochondria in cell death, which may be associated with atrophy of the hippocampus. In addition to their function in respiration, mitochondria play an important role in the regulation of cytochrome c, an apoptotic signaling element. Normally, cytochrome c resides in the intermembrane space of mitochondria, where membrane potential exists-negative inside of about 180-200mV. In response to a variety of apoptotic stimuli, mitochondria membrane potential can be changed by genomic and non-genomic cortisol action. For the non-genomic action, stress increases cortisol levels, which activates the glucocorticoid receptor (GR). Stress-activated GR directly binds to mitochondrial membranes to regulate membrane potential. The GR will also produce a genomic action, in which GR, in interacting with several other molecules (such as heat shock proteins 90/70/40, etc.), translocates into the nucleus of the cell, where it binds to DNA and exerts transcriptional action. As one of the downstream modulaters of GR activation, Bax can be up regulated and translocated to the mitochondria, where it binds to modulator of apoptosis-1 (MAP-1), a mitochondrial effector of BAX to cause change Deltapsi. These non-genomic and genomic cortisol-induced changes of the mitochondrial membrane potential can result in the release of cytochrome c from the mitochondria to the cytoplasm where the cytochrome c promotes of the action of caspases which leads to apoptosis. Therefore, we hypothesis that stress-induced changes of mitochondrial membrane potential are regulated by non-genomic and genomic actions of cortisol in hippocampal neurons. Understanding the molecular mechanism for stress-induced cell death in the hippocampus may shed a new light on developing a mitochondrial membrane potential related therapeutic drug and/or diagnostic tool for PTSD.

Animals↗
PubMed2006

Perceived safety in disaster workers following 9/11.

The perception of being safe, perceived safety, is an important component of health and the ability to work after exposure to traumatic events of all kinds. The relationship of perceived safety to posttraumatic stress disorder and depression has rarely been examined. This study examined symptoms of posttraumatic stress disorder, depression, and perceived safety in disaster workers 2 weeks after the 9/11 terrorist attacks. Perceived safety was lower in those with greater exposure (e.g., those who felt they were in physical danger, worked with dead bodies, or witnessed someone being killed or seriously injured). Lower perceived safety was associated with greater symptoms of intrusion and hyperarousal but not avoidance. Safety was negatively correlated with depression and peritraumatic dissociation. Lowered perceptions of safety following terrorist events have implications for social and work-related behaviors that can affect long-term health, morale, and productivity in disaster workers and other first responders.

Adult↗
PubMed2006

Posttraumatic stress disorder and depression in battle-injured soldiers.

OBJECTIVE: This study examined rates, predictors, and course of probable posttraumatic stress disorder (PTSD) and depression among seriously injured soldiers during and following hospitalization. METHOD: The patients were 613 U.S. soldiers hospitalized following serious combat injury. Standardized screening instruments were administered 1, 4, and 7 months following injury; 243 soldiers completed all three assessments. Cross-sectional and longitudinal analyses of risk factors were performed. PTSD was assessed with the PTSD Checklist; depression was assessed with the Patient Health Questionnaire. Combat exposure, deployment length, and severity of physical problems were also assessed. RESULTS: At 1 month, 4.2% of the soldiers had probable PTSD and 4.4% had depression; at 4 months, 12.2% had PTSD and 8.9% had depression; at 7 months, 12.0% had PTSD and 9.3% had depression. In the longitudinal cohort, 78.8% of those positive for PTSD or depression at 7 months screened negative for both conditions at 1 month. High levels of physical problems at 1 month were significantly predictive of PTSD (odds ratio=9.1) and depression at 7 months (odds ratio=5.7) when the analysis controlled for demographic variables, combat exposure, and duration of deployment. Physical problem severity at 1 month was also associated with PTSD and depression severity at 7 months after control for 1-month PTSD and depression severity, demographic variables, combat exposure, and deployment length. CONCLUSIONS: Early severity of physical problems was strongly associated with later PTSD or depression. The majority of soldiers with PTSD or depression at 7 months did not meet criteria for either condition at 1 month.

Adult↗
PubMed2006

A guide to the genetics of psychiatric disease.

The road to scientific discovery begins with an awareness of what is unknown. Research in science can in some ways be like putting together the pieces of a puzzle without having the benefit of the box-top picture of the completed puzzle. The "picture" in science is an understanding of how nature works in a particular instance, and it takes many separate pieces of the "puzzle" to put this understanding together. These pieces are always of different kinds of data, often obtained using different approaches and techniques. The challenge of the researcher is to picture or hypothesize each of the missing pieces before actually having them in hand, so they can be sought and tested in the laboratory. This "picturing" is actually having a clear idea of what you don't know: having a clear image of the "shape" of the missing piece. This is easy when the puzzle surrounding the missing piece is already in hand, but more difficult with less of it constrained by what is already known. In putting paper puzzles together, the shape of the pieces is not the only limitation that needs to be satisfied. There is also the picture to satisfy, that is, the picture usually has to make sense. In science these constraints can be manifold, and usually the quality of the research is judged by the number of ways a piece of data integrates into and brings together the rest of the puzzle. The multidimensionality of scientific questions makes it virtually essential that as many different pieces of the puzzle as possible be obtained. The more that is not known about the puzzle, the more pieces you need. Thus it is with the genetics of psychiatric diseases. In this guide, we will explore as many of the domains of the genetic puzzle as we are aware of. We will learn a bit of the language of each and how they fit into the puzzle with at least one anecdote to serve as an example. Mapping unknown territory is always a process, but we hope this guide will increase the reader's awareness of what is unknown.

Alzheimer Disease↗
PubMed2006

The impact of disasters and their aftermath on mental health.

Hurricanes Katrina and Rita were the latest disasters involving trauma to individuals and displacement of significant populations. As a consequence, those of us in health care fields often are affected both as professionals with critical skills and as individuals with families under intense stress. This Commentary, which appears in the January 2006 issue of The Journal of Clinical Psychiatry (2006;67:7-14), provides first-hand insight into the "at-the-front" realities faced by primary care professionals as disasters evolve, as well as the preparations we can make with our families and the key priorities to be addressed in our professional roles with individuals, affected groups of people, and response systems. While it is rare for us to dually publish material, we deem the importance of this information to merit joint publication in The Journal of Clinical Psychiatry and The Companion.-Larry Culpepper, M.D.

Journal Article↗
PubMed2005

Follow-up of Pentagon employees two years after the terrorist attack of September 11, 2001.

OBJECTIVE: This study examined probable posttraumatic stress disorder (PTSD) and probable depression, degree of psychological distress, and rates of mental health treatment in a sample of Pentagon staff two years after the terrorist attack of September 11, 2001. METHODS: Anonymous surveys were administered to staff at one Pentagon work center. Respondents were asked about exposure to the attack; injuries; exposure to dead bodies or families of the deceased; psychological distress; and use of mental health services. Probable PTSD and depression were assessed with the PCL-17 and the PHQ-9. RESULTS: A total of 267 responses were received. Fourteen percent of the sample had probable PTSD, and 7 percent had probable depression. Staff who were at the Pentagon on the day of the attack were more likely to have probable PTSD and probable depression. Exposure through watching television was not associated with a higher frequency of probable PTSD, probable depression, or distress. Injury during the attack was associated with a higher frequency of probable PTSD, probable depression, and distress. Respondents who were exposed to dead bodies or who acted as lay counselors to families of the deceased were more likely to have probable PTSD and depression and to report chronic distress. Of those with probable PTSD, 70 percent made at least one mental health visit during the next two years. Of those with probable depression, 74 percent reported at least one mental health visit. CONCLUSIONS: Direct exposure to the September 11 terrorist attack on the Pentagon, injury during the attack, and exposure to dead bodies or acting as a lay counselor to families of persons who were killed during the attack were all associated with higher frequencies of probable psychiatric illness and higher levels of psychological distress two years after the attack. Among survivors who had probable psychiatric illness, more than two-thirds received mental health treatment after the attack.

Adult↗
PubMed2005

Postdeployment domestic violence by U.S. Army soldiers.

The objective of this study was to determine whether a military deployment of 6 months predicted domestic violence against the wives of deployed and nondeployed soldiers during the postdeployment period. The method involved the completion of an anonymous questionnaire by a sample of the spouses of soldiers deployed from a large U.S. Army post. The Conflict Tactics Scale identified incidents of domestic violence by the soldier husbands, and a logistic regression model predicted domestic violence during the postdeployment period. The results indicate that deployment was not a significant predictor of domestic violence during the first 10 months of the postdeployment period. Younger wives and those who were victims of predeployment domestic violence were more likely to report postdeployment domestic violence. The conclusion was that interventions for domestic violence in the U.S. Army should address risks among younger couples and those with a previous incident of domestic violence.

Adult↗
PubMed2004

Use of standardized patients to enhance a psychiatry clerkship.

Changes in psychiatric health care delivery driven by such major shifts as deinstitutionalization, community-based care, and managed care have greatly altered the educational milieu for third-year psychiatry clerkships. Students may be assigned exclusively to alcohol and substance abuse treatment units, consultation-liaison services, or outpatient clinics, and may not have as broad an exposure as is desirable to patients with a variety of psychiatric illnesses. The authors describe a pilot course they developed in 2001, Clinical Psychiatric Assessment and Diagnosis, for third-year medical students at the Uniformed Services University of the Health Sciences medical school. The course uses standardized patients (SPs) to help students gain broader clinical experience. In psychiatry, a growing body of literature supports the acceptability, reliability, and validity of objective structured clinical examination assessment using SPs for medical students. Only a few articles report the use of SPs to primarily teach psychiatry instead of evaluating student proficiency in clinical psychiatry. Since this course was developed, the National Board of Medical Examiners announced that all medical students will be required to pass a clinical skills test in order to practice medicine, beginning with the class of 2005. The examination will use SPs modeling different clinical scenarios. In light of this change, many medical schools may have to reevaluate and possibly revamp their curriculums to insure sufficient acquisition of clinical skills in different specialties. The use of SPs in psychiatry could provide an effective, primary clinical teaching experience to address this new requirement as well.

Clinical Clerkship↗
PubMed2004

Psychological impact of the animal-human bond in disaster preparedness and response.

The authors present an overview of the impact of the animal-human bond on disaster management and highlight the need to further examine the relationship of animals and humans in disaster response. The human connection to animals influences compliance with individual and community evacuation plans. Search and rescue teams with canine units confront physical and emotional demands that affect both handler and animal. The culling of animal populations on a scale such as occurred during the recent foot-and-mouth epidemic in the United Kingdom affects every member of rural society. Livestock farmers and their families endure enormous emotional losses, and veterinarians and government officials who must implement these programs suffer as well. A familiarity with and understanding of these issues is important for psychiatrists and other mental health professionals who are involved in disaster preparedness and response.

Animal Welfare↗
PubMed2004

Acute stress disorder, posttraumatic stress disorder, and depression in disaster or rescue workers.

OBJECTIVE: The events of Sept. 11, 2001, highlighted the importance of understanding the effects of trauma on disaster workers. To better plan for the health care of disaster workers, this study examined acute stress disorder, posttraumatic stress disorder (PTSD), early dissociative symptoms, depression, and health care utilization in disaster workers. METHOD: Exposed disaster workers (N=207) and unexposed comparison subjects (N=421) were examined at 2, 7, and 13 months after an airplane crash. RESULTS: Exposed disaster workers had significantly higher rates of acute stress disorder, PTSD at 13 months, depression at 7 months, and depression at 13 months than comparison subjects. Those who were younger and single were more likely to develop acute stress disorder. Exposed disaster workers with acute stress disorder were 3.93 times more likely to be depressed at 7 months. Those with high exposure and previous disaster experience or who had acute stress disorder were more likely to develop PTSD. Similarly, those who were depressed at 7 months were 9.5 times more likely to have PTSD. Those who were depressed at 13 months were 7.96 times more likely to also meet PTSD criteria. More exposed disaster workers than comparison subjects obtained medical care for emotional problems at 2, 7, and 13 months. Overall, 40.5% of exposed disaster workers versus 20.4% of comparison subjects had acute stress disorder, depression at 13 months, or PTSD. CONCLUSIONS: Exposed disaster workers are at increased risk of acute stress disorder, depression, or PTSD and seek care for emotional problems at an increased rate.

Accidents, Aviation↗
PubMed2004

Posttraumatic stress disorder, depression, and perceived safety 13 months after September 11.

This study assessed relationships between exposure to the September 11, 2001, terrorist attack, current posttraumatic stress disorder (PTSD), current major depression, and current safety perceptions in a sample of 212 Pentagon staff members 13 months after the attack. Forty-eight respondents (23 percent) had possible PTSD; eight (4 percent) had probable major depression. Respondents who were directly exposed to the attack were more likely to have PTSD and major depression and were less likely to have a perception of safety at work and in usual activities and travel only. In contrast, respondents with PTSD reported a lower perception of safety at home, at work, and in usual activities and travel.

Adult↗