Nathan A Kimbrel

• PhD
• Professor (Associate) at Duke University Medical Center

Epigenetic measures of aging derived from DNA methylation are promising biomarkers associated with prospective morbidity and mortality, but require validation in real-world medical settings. Using data from 2,216 post-9/11 veterans, we examined whether accelerated DunedinPACE aging scores were associated with chronic disease morbidity, predicted he...

Background The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at...

Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis o...

Alcohol and cannabis use are each associated with suicidal thoughts and behaviors and nonsuicidal self-injury (NSSI) in military veterans, but less is known with regard to concurrent use. The present study compared US veterans (N = 1098; 78% male, 67% White) who in the past year engaged in hazardous drinking (HD only), cannabis use (CU only), or co...

Background/Aims: Predictive models of suicide risk have focused on predictors extracted from structured data found in electronic health records (EHR), with limited consideration of predisposing life events (LE) expressed in unstructured clinical text such as housing instability and marital troubles. Additionally, there has been limited work in larg...

Genome-wide association studies (GWAS) identify genetic variants underlying complex traits but are limited by stringent genome-wide significance thresholds. We present GRIN (Gene set Refinement through Interacting Networks), which increases confidence in the expanded gene set by retaining genes strongly connected by biological networks when GWAS th...

This poster outlines the associations found between COVID-19 pandemic impacts and PTSD symptom severity in a sample of U.S. Veterans.

Background Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging...

Background: Standardized definitions of suicidality phenotypes, including suicidal ideation (SI), attempt (SA), and death (SD) are a critical step towards improving understanding and comparison of results in suicide research. The complexity of suicidality contributes to heterogeneity in phenotype definitions, impeding evaluation of clinical and gen...

Background The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at...

Importance Social and environmental determinants of health (SDOH and EDOH) may contribute significantly to suicide rates among U.S. veterans. Objective To identify key predictive variables for assessing suicide-related death rates (SRR), which include suicide deaths, suicide firearm deaths, and suicide non-firearm deaths and vulnerability areas....

Prior research has established the psychometric properties of the Critical Warzone Experiences (CWE) scale among post-9/11 Iraq/Afghanistan-era veterans; however, the psychometric properties of the CWE among Gulf War I-era veterans have not yet been established. The first objective of the present study was to examine the psychometric properties of...

Cannabis use problems are on the rise in the USA, and there is a significant need for novel approaches to increase heavy cannabis users’ access to evidence-based treatment. The objective of this randomized clinical trial (RCT) was to evaluate the efficacy of mobile contingency management (mCM) to reduce cannabis use among individuals with heavy can...

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European anc...

Persons diagnosed with schizophrenia (SCZ) or bipolar I disorder (BPI) are at high risk for self-injurious behavior, suicidal ideation, and suicidal behaviors (SB). Characterizing associations between diagnosed health problems, prior pharmacological treatments, and polygenic scores (PGS) has potential to inform risk stratification. We examined self...

Background The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the M...

We present an ensemble transfer learning method to predict suicide from Veterans Affairs (VA) electronic medical records (EMR). A diverse set of base models was trained to predict a binary outcome constructed from reported suicide, suicide attempt, and overdose diagnoses with varying choices of study design and prediction methodology. Each model us...

People who experience trauma and develop posttraumatic stress disorder (PTSD) are at increased risk for poor health. One mechanism that could explain this risk is accelerated biological aging, which is associated with the accumulation of chronic diseases, disability, and premature mortality. Using data from 2309 post-9/11 United States military vet...

Importance Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans’ health, such as suicide-related behaviors and substan...

Objective To apply deep neural networks (DNNs) to longitudinal EHR data in order to predict suicide attempt risk among veterans. Local explainability techniques were used to provide explanations for each prediction with the goal of ultimately improving outreach and intervention efforts. Materials and methods The DNNs fused demographic information...

Background: Recent findings indicate that firefighters may be at increased risk for death by suicide; however, there has been only limited suicide prevention work in fire service to date. Aim: The objective of this program evaluation project was to develop and evaluate a web-based Safety Planning Intervention (SPI) training course for firefighter p...

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ance...

We present an ensemble transfer learning model to predict suicide from Veterans Affairs (VA) electronic medical records (EMR). A diverseset of base models was trained to predict a binary outcome constructed from reported suicide, suicide attempt, and overdose diagnoseswith varying choices of study design and prediction methodology. Each model used...

Introduction: Research indicates that being married is associated with reduced risk of suicide and self-directed violence (SDV) relative to being divorced. Simultaneously, difficulties within relationships predict poorer health outcomes. However, research on relationship status rarely examines relationship functioning, obfuscating the joint contri...

Background: Emergency responders are the most frequent overdose responders, however, little is known about the impact of supervised injection facility (SIF) location on first responders. The purpose of this study was to determine whether firefighter/paramedic attitudes about being stationed near an SIF were related to burnout, secondary traumatic...

Introduction Despite a recent global decrease in suicide rates, death by suicide has increased in the United States. It is therefore imperative to identify the risk factors associated with suicide attempts to combat this growing epidemic. In this study, we aim to identify potential risk factors of suicide attempt using geospatial features in an Art...

Background: First responders, including firefighters and emergency medical technicians (EMTs), are under extreme stress from repeated exposure to potentially traumatic events. To optimize treatment for this population, it is critical to understand how the various posttraumatic stress disorder (PTSD) symptom factors are associated with one another...

Firefighters are at risk for behavioral health problems; however, mental health stigma is a barrier to seeking treatment. Although effective treatments exist, many firefighters report that internal stigma prohibits presentation for effective care. This study aimed to decrease stigma about behavioral health in fire service through the development an...

Military sexual assault (MSA) is a prevalent issue among military personnel that has been linked to adverse mental and physical health outcomes, including posttraumatic stress disorder (PTSD) and suicidal thoughts and behaviors. The present study sought to investigate the relationship between MSA and nonsuicidal self-injury (NSSI) in a national sam...

Background Shame and guilt are key emotions known to amplify trauma-related symptoms in veterans. Maintenance of symptoms is facilitated by avoidance behaviors, such as substance use. However, limited research has examined the associations between shame, guilt, and substance use in daily life. Methods The current study sought to examine the cross-...

Nonsuicidal self-injury (NSSI) is a robust predictor of suicide attempts. However, understanding of NSSI and associated treatment utilization among Veterans is limited. Although impairment may be assumed, few studies examine the association between NSSI and psychosocial functioning, a core component of the rehabilitation framework of mental health....

Introduction The U.S. suicide mortality rate has steadily increased during the past two decades, particularly among military veterans; however, the epigenetic basis of suicidal thoughts and behaviors (STB) remains largely unknown. Methods To address this issue, we conducted an epigenome-wide association study of DNA methylation (DNAm) of periphera...

This handbook is currently in development, with individual articles publishing online in advance of print publication. At this time, we cannot add information about unpublished articles in this handbook, however the table of contents will continue to grow as additional articles pass through the review process and are added to the site. Please note...

Experiential avoidance (EA) is associated with posttraumatic stress disorder (PTSD) and self-injurious thoughts and behaviors (SITBs) across different populations, and extant literature has demonstrated a strong relationship between PTSD and SITBs. However, no study has explored the potential moderating role EA plays in the association of PTSD with...

Intro: Nonsuicidal self-injury (NSSI) is associated with marked functional impairment and is a robust predictor of suicide attempts. Prevalence rates of NSSI, and self-directed violence more broadly, are elevated among military veterans. Despite the inclusion of interpersonal difficulty in the diagnostic criteria for NSSI disorder, the relationshi...

Objective: Stress and stressful events are associated with poorer health, however, there are multiple ways to conceptualize and measure stress and stress responses. One physiological mechanism through which stress could result in poorer health is accelerated biological aging. This study tested which types of stress were associated with accelerated...

Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other suicidal behaviors. We performed the first GWAS of SI...

Objective: Persons diagnosed with schizophrenia (SCZ) or bipolar I disorder (BPI) are at high risk for self-injurious behavior, suicidal ideation, and suicidal behaviors (SB). Characterizing associations between diagnosed mental and physical health problems, prior pharmacological treatments, and aggregate genetic factors has potential to inform ris...

Objective: In a large multi-site cohort of Veterans who underwent Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (LSG), we compared the five-year suicidal ideation and attempt rates with matched non-surgical controls. Summary background data: Bariatric surgery has significant health benefits but has also been associated with...

Study Objectives The purpose of this study was to (1) estimate trauma associated sleep disorder (TASD) prevalence among post-9/11 era veterans and describe differences in service and comorbid mental health clinical characteristics among individuals with and without probable TASD, and (2) estimate TASD prevalence and characteristics of reported trau...

Objective: The interrelationships between cannabis use disorder (CUD), post-traumatic stress disorder (PTSD) and depressive symptoms, and non-suicidal self-injury (NSSI) were examined. Participants: Undergraduates (N = 363) who reported using cannabis within the past six months were recruited. Method: Mediation analyses was conducted to examine if...

Objective: Pain confers risk for suicidal thoughts and behaviors. Experiential avoidance (EA), which is relevant to both pain and suicide risk, has not been studied as a potential mechanism for this relationship. The present study tested the hypothesis that pain indirectly impacts suicide risk through EA in a national sample of Gulf War veterans. M...

Importance Suicide is a leading cause of death; however, the molecular genetic basis of suicidal thoughts and behaviors (SITB) remains unknown. Objective To identify novel, replicable genomic risk loci for SITB. Design, Setting, and Participants This genome-wide association study included 633 778 US military veterans with and without SITB, as ide...

Reducing Veteran rates of suicide has long remained a top priority for the Veterans Health Administration, and as such, identifying correlates of suicidal behaviors is important to develop targeted interventions. Nonsuicidal self-injury (NSSI) has been identified as a robust predictor of suicide attempts; however, less is known about correlates of...

Traumatic experiences and genetic heritability are among the most widely acknowledged risk factors leading to the development of psychopathology; including posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). The purpose of this study was to investigate if polygenic risk scores (PRS) among Veterans interacted with traumatic str...

Firefighters protect the public despite significant risk to their health and well-being stemming from frequent trauma exposure and other occupational stressors. A minority of firefighters develop posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), or related mental health problems, such as depression or anxiety. These problems frequen...

Using a four-wave longitudinal design, three competing hypotheses (i.e., social selection, social causation, and reciprocal causation) were tested pertaining to the relation between social functioning and several indices of behavioral health [i.e., post-traumatic stress symptoms (PTSS), distress, and alcohol-related problems] among military veteran...

Military service members and veterans (SMVs) are at risk for self-directed violence, including nonsuicidal self-injury (NSSI). While NSSI is an important construct worthy of independent study, it is understudied among SMVs and, when included in research, typically examined in the context of suicide risk. Consequently, lifetime prevalence rate estim...

Cannabis use has been indicated as a risk factor for suicide in veterans. This study of Gulf War veterans tested the relationship between self-report past year cannabis use and (a) past year suicidal ideation and (b) risk for suicidal behavior. Data were from a national sample (N = 1126) of Gulf War veterans. Logistic regression models indicated ca...

Military sexual assault (MSA) is a prevalent issue among military personnel that can have direct implications on postmilitary mental health. Gulf War era U.S. veterans represent the first cohort in which women veterans were integrated into most aspects of military service except for combat. The present study sought to build on prior studies by iden...

Objective Suicidal behavior is moderately heritable and a major cause of death worldwide. Two large-scale genome-wide association studies (GWAS) have recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempts (SA). The current study leveraged the genetic cohorts from these two studies to conduct the largest GWAS...

Depression and posttraumatic stress disorder (PTSD) are two of the most common mental health conditions experienced by veterans. It is unclear what individual and system level factors are associated with receiving mental health treatment for these concerns. Using a national sample of Gulf War Era veterans who endorsed lifetime diagnoses of either d...

Suicide is a major public health problem affecting US Veterans and the US in general. Many variables (e.g., demographic, clinical, biological, geographic) have been associated with risk for suicide and suicidal behavior, including altitude; however, the exact nature of the relationship between altitude and suicide remains unclear in part due to the...

Nonsuicidal self-injury (NSSI) is a robust predictor of suicidal thoughts and behaviors; however, while there are typically only small differences observed in the prevalence of NSSI between men and women, this condition has been largely overlooked and underestimated among men. Assessing NSSI methods more common in men may address misidentification...

Complementary and integrative health (CIH) approaches have gained empirical support and are increasingly being utilized among veterans to treat a myriad of conditions. A cluster of medically unexplained chronic symptoms including fatigue, headaches, joint pain, indigestion, insomnia, dizziness, respiratory disorders, and memory problems, often refe...

Analysis of longitudinal Electronic Health Record (EHR) data is an important goal for precision medicine. Difficulty in applying Machine Learning (ML) methods, either predictive or unsupervised, stems in part from the heterogeneity and irregular sampling of EHR data. We present an unsupervised probabilistic model that captures nonlinear relationshi...

Prior research suggests a possible association between attention-deficit/hyperactivity disorder (ADHD) symptoms and nonsuicidal self-injury (NSSI) in veterans. However, this association has not yet been replicated. The present study sought to replicate and expand upon this association in a gender-balanced sample of veterans (N=124), more than half...

Despite a global decrease in suicide rates in recent years, death by suicide has increased in the United States. It is therefore imperative to identify the risk factors associated with suicide attempts in order to combat this growing epidemic. In this study, we use an explainable artificial intelligence (X-AI) method, iterative Random Forest (iRF),...

Genome-wide association studies (GWAS) identify genetic variants underlying complex traits but are limited by stringent genome-wide significance thresholds. Here we dramatically relax GWAS stringency by orders of magnitude and apply GRIN (Gene set Refinement through Interacting Networks), which increases confidence in the expanded gene set by retai...

Background Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are each common among Unites States (U.S.) military veterans and frequently co-occur (i.e., PTSD+AUD). Although comorbid PTSD+AUD is generally associated with worse outcomes relative to either diagnosis alone, some studies suggest the added burden of comorbid PTSD+AUD is...

Background Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWAS). Meth...

To identify pan-ancestry and ancestry-specific loci associated with attempting suicide among veterans, we conducted a genome-wide association study (GWAS) of suicide attempts within a large, multi-ancestry cohort of U.S. veterans enrolled in the Million Veterans Program (MVP). Cases were defined as veterans with a documented history of suicide atte...

The onset and persistence of life events (LE) such as housing instability, job instability, and reduced social connection have been shown to increase risk of suicide. Predictive models for suicide risk have low sensitivity to many of these factors due to under-reporting in structured electronic health records (EHR) data. In this study, we show how...

Introduction: Nonsuicidal self-injury (NSSI) is associated with significant impairment and is a robust predictor of suicidal ideation, attempts, and death by suicide; however, the present lack of a brief screening instrument for NSSI coupled with consistent underidentification of NSSI in male adults has led to concerning rates of missed identifica...

Purpose Posttraumatic Stress Disorder (PTSD) is associated with increased alcohol use and alcohol use disorder (AUD), which are all moderately heritable. Studies suggest the genetic association between PTSD and alcohol use differs from that of PTSD and AUD, but further analysis is needed. Basic Procedures We used genomic Structural Equation Modeli...

Ecological momentary assessment (EMA) is a useful tool to investigate antecedents and consequences of nonsuicidal self-injury (NSSI), a robust predictor of Veteran suicide risk. Despite elucidating temporal changes among dynamic variables, EMA remains underutilized to study NSSI among veterans, perhaps due to concerns of safety and utility. The pre...

The onset and persistence of life events (LE) such as housing instability, job instability, and reduced social connection have been shown to increase risk of suicide. Predictive models for suicide risk have low sensitivity to many of these factors due to under-reporting in structured electronic health records (EHR) data. In this study, we show how...

Suicide is a major public health problem affecting US Veterans and the US in general. Many variables (e.g., demographic, clinical, biological, geographic) have been associated with risk for suicide and suicidal behavior, including altitude; however, the exact nature of the relationship between altitude and suicide remains unclear in part due to the...

Nonsuicidal self-injury (NSSI) has been identified as one of the strongest predictors of suicide attempts. Wall/object punching is a particularly prevalent form of NSSI among male veterans that has been linked to both impulsivity and anger. The objective of the present study was to examine the indirect effect of impulsivity on wall/object punching...

Analysis of longitudinal Electronic Health Record (EHR) data is an important goal for precision medicine. Difficulty in applying Machine Learning (ML) methods, either predictive or unsupervised, stems in part from the heterogeneity and irregular sampling of EHR data. We present an unsupervised probabilistic model that captures nonlinear relationshi...

The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and fu...

Background The affective states most strongly associated with nonsuicidal self-injury (NSSI) remain poorly understood, particularly among veterans. This study used ecological momentary assessment (EMA) to examine relationships between affect ratings and NSSI urges and behaviors among veterans with NSSI disorder. Methods Participants (N = 40) compl...

Child maltreatment is a well-established risk factor for suicide attempts, but research on mechanisms accounting for this relationship is needed. The current study examined the indirect effects of posttraumatic stress disorder (PTSD) symptoms and alcohol misuse in the relationship between childhood maltreatment and suicidal ideation. In the current...

A substantial minority of deployed Gulf War veterans developed posttraumatic stress disorder (PTSD), depression, and several chronic illnesses. Although military combat and exposure to certain nuclear, biological, and chemical agents (NBCs) increase risk for post-deployment health problems, they do not fully explain many Gulf War veteran health dia...

Objectives As a malleable risk-factor, psychological inflexibility is implicated in the development and maintenance of posttraumatic stress symptoms (PTS). Unfortunately, limited research has addressed whether changes in psychological inflexibility are antecedent to changes in PTS severity over time, or whether such changes are mutually dependent....

Background Suicide is a leading cause of death worldwide, and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genom...

Background Worldwide, nearly 800,000 individuals die by suicide each year; however, longitudinal prediction of suicide attempts remains a major challenge within the field of psychiatry. The objective of the present research was to develop and evaluate an evidence-based suicide attempt risk checklist [i.e., the Durham Risk Score (DRS)] to aid clinic...

Posttraumatic stress disorder (PTSD) is a complex psychiatric disorder that can develop following exposure to traumatic events. The Psychiatric Genomics Consortium PTSD group (PGC-PTSD) has collected over 20,000 multi-ethnic PTSD cases and controls and has identified both genetic and epigenetic factors associated with PTSD risk. To further investig...

Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symp...

Due to occupational stress and exposure to potentially traumatic events, firefighters are at an increased risk for the development of many behavioral health conditions. While volunteer and career firefighters represent two distinct subgroups, little research has examined differences in the availability of, and barriers to, behavioral health care be...

Background Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensit...

An association has been found between cannabis use disorder (CUD) and violence in several clinical populations, including veterans with posttraumatic stress disorder (PTSD), and there is evidence that CUD has been increasing among veterans since September 11, 2001. There is also evidence that some veterans may be attempting to self-medicate psychol...