Murray B Stein's research while affiliated with Naval Medical Center San Diego and other places

Publications (990)

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Background The prognostic value of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) as day-of-injury predictors of functional outcome after traumatic brain injury is not well understood. GFAP is a protein found in glial cells and UCH-L1 is found in neurons, and these biomarkers have been cleared to aid in decisi...
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Introduction Active duty service members transitioning to civilian life can experience significant readjustment stressors. Over the past two decades of the United States’ longest sustained conflict, reducing transitioning veterans’ suicidal behavior and homelessness became national priorities. However, it remains a significant challenge to identify...
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Background The presentation, etiology, and relative risk of psychiatric disorders are strongly influenced by biological sex. Neuroticism is a transdiagnostic feature of psychiatric disorders displaying prominent sex differences. We performed genome-wide association studies (GWAS) of neuroticism separately in males and females to identify sex-specif...
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Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 studies with 88,316 MD cases and 902,757 controls to previously reported data from individuals of European ancestry. This includes samples of African (36% of effect...
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Genome-wide association studies (GWAS) have identified several risk loci for post-traumatic stress disorder (PTSD); however, how they confer PTSD risk remains unclear. We aimed to identify genes that confer PTSD risk through their effects on brain protein abundance to provide new insights into PTSD pathogenesis. To that end, we integrated human bra...
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Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (...
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Insomnia is a heritable, highly prevalent sleep disorder for which no sufficient treatment currently exists. Previous genome-wide association studies with up to 1.3 million subjects identified over 200 associated loci. This extreme polygenicity suggested that many more loci remain to be discovered. The current study almost doubled the sample size t...
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Importance: Mild traumatic brain injury (mTBI) may impair the ability to work. Strategies to facilitate return to work are understudied. Objective: To assess employment and economic outcomes for employed, working-age adults with mTBI in the 12 months after injury and the association between return to work and employer assistance. Design, settin...
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Over 75% of patients presenting to level 1 trauma centers in the U.S. with suspicion of TBI sufficient to require a clinical computed tomography scan report injury-related symptoms 3 months later. There are currently no approved treatments, and few clinical trials have evaluated possible treatments. Efficient trials will require subject inclusion a...
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Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as...
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Importance: Approximately one-third of US soldiers who attempt suicide have not received a mental health diagnosis (MH-Dx) before their suicide attempt (SA), yet little is known about risk factors for SA in those with no MH-Dx. Objective: To examine whether premilitary mental health is associated with medically documented SA among US Army soldie...
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Background The transition from military service to civilian life is a high-risk period for suicide attempts (SAs). Although stressful life events (SLEs) faced by transitioning soldiers are thought to be implicated, systematic prospective evidence is lacking. Methods Participants in the Army Study to Assess Risk and Resilience in Servicemembers (ST...
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DTI literature on single-center studies contains conflicting results regarding acute effects of mTBI on WM microstructure and their prognostic significance. This larger-scale multicenter DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From TRACK-TBI, a cohort study a...
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Objective: Among U.S. Army soldiers suicide attempts (SAs) are a significant public health concern, particularly early in service. We examined the association of attachment style with SA and suicide ideation (SI) among U.S. Army soldiers. Methods: We analyzed survey data from new soldiers who participated in the Army Study to Assess Risk and Res...
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Importance Alcohol genome-wide association studies (GWAS) have generally focused on alcohol consumption and alcohol use disorder (AUD); few have examined habitual drinking behaviors like maximum habitual alcohol intake (MaxAlc). Objective Identify MaxAlc loci and elucidate the genetic architecture across alcohol traits. Design The MaxAlc GWAS was...
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Previous research has implicated reductions in anxiety sensitivity (AS) – the dispositional tendency to fear anxiety-related sensations – as critical to change during cognitive behavioral therapy (CBT) for anxiety. However, the relationship of AS to anxiety symptom remittance following CBT remains largely unknown. To address this gap, the current s...
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The widespread comorbidity among psychiatric disorders (PDs) demonstrated in epidemiological studies is mirrored by non-zero, positive genetic correlations from large scale genetic studies. We employed several strategies to uncover pleiotropic SNPs, genes and biological pathways underlying this genetic covariance. First, we conducted cross-trait me...
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Many individuals with posttraumatic stress disorder (PTSD) report increased negative affect (NA) and decreased positive affect (PA). Little is known about whether treatments for PTSD improve PA. We conducted a secondary analysis of a randomized clinical trial comparing integrated exposure therapy (I-PE) to integrated coping skills therapy (I-CS) fo...
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Introduction The ability to predict and prevent homelessness has been an elusive goal. The purpose of this study was to develop a prediction model that identified U.S. Army soldiers at high risk of becoming homeless after transitioning to civilian life based on information available before the time of this transition. Methods The prospective cohor...
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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...
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UK Biobank (UKB) is a key contributor in mental health genome-wide association studies (GWAS) but only ~31% of participants completed the Mental Health Questionnaire (“MHQ responders”). We predicted generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and major depression symptoms using elastic net regression in the ~69% of UKB...
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Background The association between coronary artery disease (CAD) and posttraumatic stress disorder (PTSD) contributes to the high morbidity and mortality observed among affected individuals. To understand the dynamics underlying PTSD-CAD comorbidity, we conducted a genetically-informed causal inference analysis using large-scale genome-wide associa...
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Background The presentation, etiology, and relative risk of psychiatric disorders are strongly influenced by biological sex. Neuroticism is a transdiagnostic feature of psychiatric disorders displaying prominent sex differences. We performed genome-wide association studies (GWAS) of neuroticism separately in males and females to identify sex-specif...
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Full-text available
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 PT...
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Suicide risk is elevated among military service members who recently transitioned to civilian life. Identifying high-risk service members before this transition could facilitate provision of targeted preventive interventions. We investigated the feasibility of doing this by attempting to develop a prediction model for self-reported suicide attempts...
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Background Factors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias. Methods...
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Posttraumatic stress disorder (PTSD) is a psychiatric disorder that may arise in response to severe traumatic event and is diagnosed based on three main symptom clusters (reexperiencing, avoidance, and hyperarousal) per the Diagnostic Manual of Mental Disorders (version DSM-IV-TR). In this study, we characterized the biological heterogeneity of PTS...
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Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, a...
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Background Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). Methods Neuroimaging and clinical data were aggregated fro...
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Background Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients’ outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good perfor...
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Background Posttraumatic stress disorder (PTSD) is triggered by environmental stressors. Empathy may predispose an individual to respond to life events differently if high empathizers are emotionally more sensitive to trauma. For the first time, we test this hypothesis using genetic information. Methods We applied polygenic scoring (PGS) to invest...
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Symptom endorsement after traumatic brain injury (TBI) is common acutely post-injury and is associated with other adverse outcomes. Prevalence of persistent symptoms has been debated, especially in mild TBI (mTBI). A cohort of participants > 17 years with TBI (n=2,039), 257 orthopedic trauma controls (OTC), and 300 friend controls (FC) were enrolle...
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Background: The mental disorders included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were depressive disorders, anxiety disorders, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, eating disorders, idiopathic developmental intellectual disabili...
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Background Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD. Method Adult subjects (N = 2229; 56.2% male) aged 18–69...
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Importance Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known. Objective To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological...
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Background: Population-based data on risk factors for suicide attempts among veterans remains limited. Methods: A national probability sample of 2307 veterans was followed over the course of four timepoints spanning seven years to examine how a range of baseline risk factors predict incident suicide attempt. Suicide attempt data were aggregated in...
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Introduction Emotion reactivity (ER) and distress intolerance (DI) may be associated with increased suicide attempt (SA) risk among U.S. Army soldiers. Method In this case–control study, 74 soldiers recently hospitalized for SA (cases) were compared with 133 control soldiers from the same Army installations selected based on either propensity scor...
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Background: Despite progress in youth anxiety assessment, there is need for a measure that is simultaneously (a) free, (b) brief, (c) focused broadly on anxiety and avoidance severity, frequency, and interference, and (d) concerned with the past week. The adult Overall Anxiety Severity and Impairment Scale (OASIS) was adapted to yield a caregiver-...
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Background Problematic anger is frequently reported by soldiers who have deployed to combat zones. However, evidence is lacking with respect to how anger changes over a deployment cycle, and which factors prospectively influence change in anger among combat-deployed soldiers. Methods Reports of problematic anger were obtained from 7298 US Army sol...
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Importance Rates of suicidal thoughts and behaviors (STBs) in US soldiers have increased sharply since the terrorist attacks on September 11, 2001, and postdeployment posttraumatic stress disorder (PTSD) remains a concern. Studies show that soldiers with greater combat exposure are at an increased risk for adverse mental health outcomes, but little...
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Objectives Major Depressive Disorder (MDD) is a complex neuropsychiatric disease with known genetic associations, but without known links to rare variation in the human genome. Here we aim to identify rare genetic variants associated with MDD using deep whole-genome sequencing data in an independent population. Methods We report the sequencing of...
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Altered approach motivation is hypothesized to be critical for the maintenance of depression. Computer-administered approach-avoidance training programs to increase approach action tendencies toward positive stimuli produce beneficial outcomes. However, there have been few studies examining neural changes following approach-avoidance training. Part...
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Objectives. To examine associations of current mental and substance use disorders with self-reported gun ownership and carrying among recently separated US Army soldiers. Veterans have high rates of both gun ownership and mental disorders, the conjunction of which might contribute to the high suicide rate in this group. Methods. Cross-sectional sur...
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The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through th...
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Traumatic brain injury (TBI) is associated with a host of psychiatric and neurobehavioral problems. As mortality rates have declined for severe TBI, attention has turned to the cognitive, affective, and behavioral sequelae of injuries across the severity spectrum, which are often more disabling than residual physical effects. Moderate and severe TB...
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Importance Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. Objective To investigate the genetics of depression among individual...
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Importance Anger is linked to adverse outcomes in military populations; however, whether pre-enlistment anger attacks are associated with postenlistment mental disorders and suicidality is unknown. Objective To explore the associations of pre-enlistment anger attacks with postenlistment mental health. Design, Setting, and Participants In this obs...
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Purpose: The interplay between critical illness and mental disorders is poorly understood. The purpose of this study is to measure both the treated prevalence of mental disorders and psychotropic medication use before and after hospitalization and the impact of intensive care unit (ICU) admission on these outcomes. Methods: Using a population-ba...
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Objective: The authors sought to identify predictors of imminent suicide attempt (within 30 days) among U.S. Army soldiers following their first documented suicidal ideation. Methods: Using administrative data from the Army Study to Assess Risk and Resilience in Servicemembers, the authors identified 11,178 active-duty Regular Army enlisted sold...
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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...
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It is important to measure quality of life (QoL) after traumatic brain injury (TBI), yet limited studies have compared QoL inventories. In N=2,579 TBI, orthopedic trauma control, and healthy friend control participants, we compared the Quality of Life After Brain Injury-Overall Scale (QOLIBRI-OS), developed for TBI patients, to the Satisfaction wit...
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Objective: US military veterans have high rates of suicide relative to civilians. However, little is known about the prevalence and correlates of suicidal behaviors in the general US veteran population. Methods: Data were from the National Health and Resilience in Veterans Study, a representative survey of US veterans conducted in 2019-2020 (n = 4...
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Multiple psychiatric disorders have been associated with abnormalities in both the innate and adaptive immune systems. The role of these abnormalities in pathogenesis, and whether they are driven by psychiatric risk variants, remains unclear. We tested for enrichment of GWAS variants associated with multiple psychiatric disorders (cross-disorder or...
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Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnorma...
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A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for,...
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There are currently no validated pharmacotherapies for posttraumatic stress disorder (PTSD)-related insomnia. The purpose of the National Adaptive Trial for PTSD-Related Insomnia (NAP Study) is to efficiently compare to placebo the effects of three insomnia medications with different mechanisms of action that are already prescribed widely to vetera...