Linda M Bierer

Linda M Bierer
U.S. Department of Veterans Affairs | VA · Mental Health Services

MD

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137
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Publications

Publications (137)
Article
Background The hippocampus and cingulate gyrus are strongly interconnected brain regions that have been implicated in the neurobiology of post-traumatic stress disorder (PTSD). These brain structures are comprised of functionally distinct subregions that may contribute to the expression of PTSD symptoms or associated cardio-metabolic markers, but h...
Article
Background Brain-derived neurotrophic factor (BDNF) plays a central role in brain development and plasticity and has been demonstrated to be altered in neuropsychiatric diseases and suicidal behavior. We examined whether there is a difference with regard to plasma BDNF levels between veterans who made or did not make a suicide attempt post-deployme...
Article
Full-text available
Despite experiencing a significant trauma, only a subset of World Trade Center (WTC) rescue and recovery workers developed posttraumatic stress disorder (PTSD). Identification of biomarkers is critical to the development of targeted interventions for treating disaster responders and potentially preventing the development of PTSD in this population....
Article
Attempts to correlate blood levels of brain-derived neurotrophic factor (BDNF) with post-traumatic stress disorder (PTSD) have provided conflicting results. Some studies found a positive association between BDNF and PTSD diagnosis and symptom severity, while others found the association to be negative. The present study investigated whether serum l...
Article
Full-text available
Epigenetic changes are currently invoked as explanations for both the chronicity and tenacity of post-traumatic stress disorder (PTSD), a heterogeneous condition showing varying, sometimes idiosyncratic responses to treatment. This study evaluated epigenetic markers in the context of a randomized clinical trial of PTSD patients undergoing prolonged...
Article
Objective Cognitive behavioral therapies such as Prolonged Exposure (PE) are considered first line treatments for posttraumatic stress disorder (PTSD). Nonetheless, many continue to experience significant symptoms following treatment and there is interest in enhancing treatment effectiveness. Glucocorticoid alterations in PTSD are well documented,...
Preprint
Full-text available
Despite experiencing a significant trauma, only a subset of World Trade Center (WTC) rescue and recovery workers developed posttraumatic stress disorder (PTSD). Identification of biomarkers is critical to the development of targeted interventions for treating disaster responders and potentially preventing the development of PTSD in this population....
Preprint
Full-text available
Post-traumatic stress disorder (PTSD) results from severe trauma exposure, but the extent to which genetic and epigenetic risk factors impact individual clinical outcomes is unknown. We assessed the impact of genomic differences following glucocorticoid administration by examining the transcriptional profile of human induced pluripotent stem cell (...
Preprint
Full-text available
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition occurring in individuals exposed to trauma. The study of PTSD is complicated by highly heterogeneous presentations and experiences of trauma. Here, we studied genetic correlates of PTSD and resilience among a group of responders to the World Trade Center (WTC) 9/11/2001 a...
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Offspring of trauma survivors are more likely to develop PTSD, mood, and anxiety disorders and demonstrate endocrine and molecular alterations compared to controls. This study reports the association between parental Holocaust exposure and genome-wide gene expression in peripheral blood mononuclear cells (PBMC) from 77 Holocaust survivor offspring...
Article
Combat exposure has been linked to increased risk of suicidal ideation, suicide attempts, and death by suicide, and suicidality has been linked with altered testosterone levels. In this study, we examined morning baseline free and total testosterone levels and the effect of dexamethasone administration on testosterone levels in male combat veterans...
Article
War veterans are at increased risk of suicide that may be related to deployment and/or post-deployment stressors and to adjustment-related factors. The aim of this study was to examine whether levels of plasma neuropeptide Y (NPY) might distinguish combat veterans who have made a post-deployment suicide attempt from those who have never made a suic...
Article
Although glucocorticoid resistance contributes to increased inflammation, individuals with post-traumatic stress disorder (PTSD) exhibit increased glucocorticoid receptor (GR) sensitivity along with increased inflammation. It is not clear how inflammation co-exists with a hyper-responsive hypothalamic pituitary adrenal axis (HPA axis). To understan...
Article
Objective: There is growing evidence that exposure to trauma prior to conception can affect offspring. The authors have reported that adult offspring of Holocaust survivors showed lower methylation of FK506 binding protein 5 (FKBP5) intron 7, site 6 compared with Jewish comparison volunteers. The present study sought to replicate this finding in a...
Article
Full-text available
This Article was originally published without the correct Supplemental Table file (Table S1 was missing). In total, there are seven Supplemental Tables, and six were in the original submission. Furthermore, Fig. 1 was misplaced in the main text; it was embedded in the manuscript file even before the results section. Both issues have now been fixed...
Article
Full-text available
Post-traumatic stress disorder (PTSD) is a condition of stress reactivity, whose clinical manifestations are evident when patients are triggered following exposure to a traumatic event. While baseline differences in gene expression of glucocorticoid signaling and inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) have been associa...
Article
Combat veterans are at elevated suicide risk. The goal of this study was to test the hypothesis that combat veterans who have made a suicide attempt post-deployment can be distinguished from combat veterans who have never made a suicide attempt based on differences in psychological and biological variables. For the latter, we focused on endogenous...
Preprint
Full-text available
Although glucocorticoid resistance contributes to increased inflammation, individuals with post-traumatic stress disorder (PTSD) exhibit increased glucocorticoid receptor (GR) sensitivity along with increased inflammation. It is not clear how inflammation co-exists with a hyper-responsive hypothalamic pituitary adrenal axis (HPA axis). To understan...
Article
Full-text available
Posttraumatic stress disorder (PTSD) is associated with impaired major domains of psychology and behavior. Individuals with PTSD also have increased co-morbidity with several serious medical conditions, including autoimmune diseases, cardiovascular disease, and diabetes, raising the possibility that systemic pathology associated with PTSD might be...
Data
Supplementary methods and results metabolomics in PTSD. Table A. Analytes identified in the discovery group that were not significantly different between PTSD positive and PTSD negative subjects Figure A. Barplot of metabolite validation success fraction over 1000 permutations of discovery and test groups. (DOCX)
Data
Metabolomics PTSD database PLoS One. This file contains the primary demographic and metabolomic data reported in this manuscript. (XLSX)
Article
Full-text available
Posttraumatic stress disorder (PTSD) is associated with abnormalities in functional connectivity of a specific cortico-limbic network; however, less is known about white matter abnormalities providing structural connections for this network. This study investigated whether the diagnosis and symptoms of PTSD are associated with alterations in fracti...
Article
Objective The goal of this study was to determine whether combat veterans who have made a suicide attempt postdeployment can be distinguished from combat veterans who have never made a suicide attempt based on differences in psychological and biological variables. Methods Demographic and clinical parameters of suicide attempters and non‐attempters...
Article
Full-text available
There has been great interest in the possibility that effects of trauma might be passed from parent to offspring through epigenetic mechanisms. This topic has stimulated discussion and controversy in the scientific literature, the popular press, and culture at large. This article describes the initial observations that have led to recent examinatio...
Article
Inflammation is reported in post-traumatic stress disorder (PTSD). Few studies have investigated circulating blood cells that may contribute to inflammation. We assessed circulating platelets, white blood cells (WBC) and red blood cells (RBC) in PTSD and assessed their relationship to inflammation and symptom severity. One-hundred and sixty-three m...
Article
Posttraumatic stress disorder (PTSD) is associated with increased risk for Type 2 diabetes and cardiovascular disease (cardiometabolic disease), warranting research into targeted prevention strategies. In the present case-control study of 160 young (mean age 32.7 years) male military veterans, we aimed to assess whether PTSD status predicted increa...
Article
Introduction: Several lines of evidence indicate that increased inflammation is associated with Post-Traumatic Stress Disorder (PTSD). We have previously reported that peripheral inflammatory markers are significantly higher in combat-exposed veterans with than without PTSD. This study was designed to replicate these findings in a new study cohort...
Article
Introduction: Post-traumatic stress disorder (PTSD) has been associated with immune disturbances, including a higher incidence of infections and autoimmune diseases as well as a net pro-inflammatory state. Natural killer (NK) cells, a key component of the innate immune system, have been less well-studied in PTSD despite their importance in immunit...
Article
Introduction: Psychiatric, physical and biological aspects of posttraumatic stress disorder (PTSD) may be associated with dysfunctions in several cellular processes including nitric oxide (NO) production. NO is synthesized from arginine in a reaction carried out by NO synthase (NOS) enzymes. The recently introduced "global arginine bioavailability...
Article
Background Circulating hematopoietic progenitor cells (PCs; CD34+ and CD34+/KDR+) facilitate neurogenesis and neovascularization, promoting increased cortical thickness and white matter integrity in animal models. However, it unknown whether low PCs are associated with trauma symptoms or neurovascular health among veterans. Objectives Determine whe...
Article
Sexual dysfunction is not a symptom of PTSD but is a common clinical complaint in trauma survivors with this disorder. In that there are biological parallels in the neuroendocrine processes underlying both PTSD and sexual behavior, we conducted an exploratory investigation of the relationship of PTSD and related neuroendocrine indicators with sexua...
Article
Background: The involvement of epigenetic mechanisms in intergenerational transmission of stress effects has been demonstrated in animals but not in humans. Methods: Cytosine methylation within the gene encoding for FK506 binding protein 5 (FKBP5) was measured in Holocaust survivors (n = 32), their adult offspring (n = 22), and demographically c...
Article
The identification of biomarkers for post-traumatic stress disorder (PTSD) and resilience/recovery is critical for advancing knowledge about pathophysiology and treatment in trauma-exposed persons. This study examined a series of glucocorticoid-related biomarkers prior to and in response to psychotherapy. Fifty-two male and female veterans with PTS...
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Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal posttraumatic stress disorder (PTSD) appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association...
Article
Background: Chronic inflammation may be involved in combat-related post-traumatic stress disorder (PTSD) and may help explain comorbid physical diseases. However, the extent to which combat exposure per se, depression, or early life trauma, all of which are associated with combat PTSD, may confound the relationship between PTSD and inflammation is...
Article
Objective: Differential effects of maternal and paternal posttraumatic stress disorder (PTSD) have been observed in adult offspring of Holocaust survivors in both glucocorticoid receptor sensitivity and vulnerability to psychiatric disorder. The authors examined the relative influences of maternal and paternal PTSD on DNA methylation of the exon 1...
Article
Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinar...
Article
Background Enhanced glucocorticoid receptor (GR) sensitivity is present in people with PTSD, but the molecular mechanisms of GR sensitivity are not understood. Epigenetic factors have emerged as one potential mechanism that account for how trauma exposure leads to sustained PTSD symptomatology given that PTSD develops in only a subset of trauma sur...
Article
Full-text available
Epigenetic alterations offer promise as prognostic or diagnostic markers, but it is not known whether these measures associate with, or predict, clinical state. These questions were addressed in a pilot study with combat veterans with PTSD to determine whether cytosine methylation in promoter regions of the glucocorticoid related NR3C1 and FKBP51 g...
Article
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Background : The identification of molecular post-traumatic stress disorder (PTSD) susceptibility pathways associated with different patterns of behavioral response to trauma is essential to an understanding of the neurobiology of PTSD and can pave the design for new treatments. Although several genes have been reported to be differentially express...
Article
Rational: Increased GR sensitivity has been associated with PTSD severity in several studies, and in a recent report, was found to predict the extent of improvement in severity of PTSD symptoms from pre- to post-treatment. These findings provided the rational for an investigation of two GR genotype polymorphisms know to affect GR sensitivity in rel...
Article
Rationale/statement of the problem : Neuropeptide Y (NPY) is a peptide with behaviorally relevant effects on the hippocampus and is thought to function as an endogenous anxiolytic. In prior work, we reported that veterans who had recovered from combat-related post-traumatic stress disorder (PTSD) had higher levels than those who were not combat exp...
Article
Full-text available
Background: Suicidal behavior is a critical problem among military veterans. Therefore, it is important to identify psychological suicide risk factors that are unique for veterans of military service. We compared clinical features of 55 veteran suicide attempters with 55 veterans without a history of suicide attempts. Methods: Demographic and clini...
Article
Introduction: Posttraumatic stress disorder (PTSD) is a complex disorder associated with an intricate biological and psychological symptom profile and various common comorbidities. Despite an existing myriad of evidence-based and experimental treatments, PTSD is often difficult to treat. This reality necessitates a discussion of the potential of e...
Article
Full-text available
We have previously reported the differential expression of 17 probe sets in survivors of the 9/11 attacks with current posttraumatic stress disorder (PTSD) compared to similarly exposed survivors with no lifetime PTSD. The current study presents an expanded analysis of these subjects, including genotype at FKBP5, a modulator of glucocorticoid recep...
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Although the link between chronic stress and the development of cardiovascular and metabolic diseases of adulthood has been known for some time, there is growing recognition that early environmental influences may result in developmental programming via epigenetic mechanisms, thereby affecting the developmental trajectory of disease progression. Pr...
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Prolonged exposure (PE) therapy has been found to reduce symptoms of posttraumatic stress disorder (PTSD); however, it is difficult for many patients to engage fully in the obligatory retelling of their traumatic experiences. This problem is compounded by the fact that habituation and cognitive restructuring - the main mechanisms through which PE i...
Article
Neuroendocrine, cognitive and hippocampal alterations have been described in Gulf War (GW) veterans, but their inter-relationships and significance for posttraumatic stress disorder (PTSD) have not been described. Hydrocortisone (Hcort) was administered to GW veterans with (PTSD+ n=12) and without (PTSD- n=8) chronic PTSD in a randomized, placebo-c...
Article
Combat veterans with posttraumatic stress disorder (PTSD) demonstrate less robust improvement following treatments than do civilians with PTSD. This paper discusses a theoretical model for evaluating treatment response based on the extent of change in biological markers of symptom severity or resilience between treatment initiation and termination....
Article
Epigenetic modifications, such as DNA methylation, can occur in response to environmental influences to alter the functional expression of genes in an enduring and potentially, intergenerationally transmissible manner. As such, they may explain interindividual variation, as well as the long-lasting effects of trauma exposure. Although there are cur...
Article
A proportion of subjects with symptoms of posttraumatic stress disorder (PTSD) are unresponsive to specialized psychotherapy, but a biological basis for this has not been described. To observe whether differences in cortisol or its metabolites predict or correlate with response to therapy for PTSD symptoms, cortisol and its metabolites were measure...
Article
In animal models, early life exposure to major environmental challenges such as malnutrition and stress results in persisting cardiometabolic, neuroendocrine and affective effects. While such effects have been associated with pathogenesis, the widespread occurrence of 'developmental programming' suggests it has adaptive function. Glucocorticoids ma...
Article
A significant association between parental PTSD and the occurrence of PTSD in offspring has been noted, consistent with the idea that risk for the development of PTSD is transmitted from parent to child. Two recent reports linking maternal PTSD and low offspring cortisol prompted us to examine the relative contributions of maternal vs. paternal PTS...
Article
Parental posttraumatic stress disorder (PTSD) appears to be a relevant risk factor for the development of PTSD, as evidenced by a greater prevalence of PTSD, but not trauma exposure, in adult offspring of Holocaust survivors with PTSD, compared to children of Holocaust-exposed parents without PTSD. This paper summarizes recent neuroendocrine studie...
Article
Lower cortisol levels in posttraumatic stress disorder (PTSD) may reflect a preexisting vulnerability associated with developing the disorder after trauma exposure. Because offspring of trauma survivors with PTSD have a greater prevalence of PTSD after their own life events than offspring of trauma survivors without PTSD and offspring of nonexposed...
Article
The authors used a low-dose dexamethasone suppression test to examine the effect of a PTSD risk factor, parental PTSD, on cortisol negative feedback inhibition in adult offspring of Holocaust survivors with PTSD (N=13) versus without PTSD (N=12) as well as a comparison group of offspring whose parents had no Holocaust exposure (N=16). Blood samples...