Etiology Of Posttraumatic Stress Disorder Research Articles

Paradoxical effect of anti-inflammatory drugs on IL-6 mRNA expression in patients with PTSD during treatment.

The pathophysiology of posttraumatic stress disorder (PTSD) is associated with the activation of the innate immune system, including cytokines like interleukin 6 (IL-6). However, the role of IL-6 in the etiology and treatment of PTSD still remains elusive. We conducted a prospective controlled trial to investigate the development of IL-6 during psychosomatic treatment in individuals with PTSD in comparison with individuals without PTSD. We assessed IL-6 mRNA expression before and after 2 months of psychosomatic treatment in individuals with and without PTSD. Severities of PTSD and depressive symptoms were assessed in parallel. Linear mixed regression was applied for statistical analysis, including the factors diagnosis PTSD and pre-post treatment after subgrouping for intake of anti-inflammatory drugs. The development of IL-6 mRNA expression during treatment was affected by the use of anti-inflammatory drugs. In the subgroup without intake of anti-inflammatory drugs, no significant statistical treatment effect in individuals with and without PTSD emerged. In the subgroup of individuals taking anti-inflammatory drugs, a significant interaction effect of the factors pre-post treatment and diagnosis PTSD was observed. Whereas IL-6 mRNA expression in individuals without PTSD decreased according to amelioration of symptoms, IL-6 mRNA expression in individuals with PTSD increased significantly during treatment, in opposite direction to symptom severity. Anti-inflammatory drugs might affect IL-6 mRNA expression in individuals with PTSD in a paradoxical way. This study offers a further piece of evidence that IL-6 could be involved in the pathophysiology of PTSD and PTSD-specific immunologic molecular mechanisms.

Post-traumatic Stress Disorder: The Influence of the Environmental Context and Analysis of Oxidative Stress and Inflammatory and Glycemic Markers in Women Living in Kurdistan Regional Government-Iraq.

Background Internally displaced persons (IDP) camps are still home to a large number of female survivors of the Yazidi genocide carried out in Iraq in 2014 by the Islamic organization known as the Islamic State of Iraq and Syria (ISIS). Many of these women suffer from a persistent form of post-traumatic stress disorder (PTSD), which can last for many years. On the other hand, little is known about the intricate etiology of PTSD. Objectives In this observational cross-sectional study, the biochemical parameters, including inflammatory and oxidative stress (OXS) markers, were evaluated in two groups: the case group (women with newly diagnosed PTSD) and the control group (apparently healthy women). Furthermore, how the environment impacts the biochemical and OXS parameters of people not diagnosed with PTSD but living in IDP camps was also analyzed. Materials and methods The PTSD group (n=55, age=30.0 years) was made up of women survivors of genocide-related events living in IDP camps in the Kurdistan region of Iraq. The studied parameters in the PTSD group have been compared to two healthy control groups: (1) internal control group (n=55, age=28.1 years): healthy women living inside the IDP camps; and (2) external control group (n=55, age=28.3 years): healthy women living outside the IDP camps. The diagnosis of PTSD was conducted using a validated Kurdish version of the PTSD Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (PCL-5) scale. Blood samples were collected to determine the level of glycated hemoglobin (HbA1c) and the concentrations of fasting serum glucose (FSG), C-reactive protein (CRP), ceruloplasmin (CP), 8-hydroxydeoxyguanosine (8-OHdG), glutathione (GSH), malondialdehyde (MDA), protein carbonyls (PC), and catalase (CAT) activity. Results Women with PTSD presented increased values of FSG (4.41%, p<0.05), HbA1c (4.74%, p<0.05), and CRP (114.29%, p<0.05), as well as increased levels of 8-OHdG (185.97%, p<0.001), CP (27.08%, p<0.001), MDA (141.97%, p<0.001), and PC (63.01%, p<0.001), besides increased CAT activity (121.5%, p<0.001), when compared with the control groups. A significant reduction of GSH (-20.33%, p<0.05) was observed in PTSD patients as compared to the external control group. In relation to the internal control group, women diagnosed with PTSD presented significantly increased levels of FSG (3.88%, p<0.05), HbA1c (2.83%, p<0.05), CRP (77.97%, p<0.05), and PC (41.3%, p<0.05), as well as increased levels of 8-OHdG (118.84%, p<0.001), CP (22.72%, p<0.001), MDA (90.67%, p<0.001), and CAT activity (55.31%, p<0.001). Healthy individuals residing in IDP camps, compared with external healthy control, presented significantly elevated levels of 8-OHdG (30.68%, p<0.001), MDA (26.91%, p<0.001), PC (15.37%, p<0.001), and CAT activity (42.62%, p<0.001). Conclusion Our findings indicate that PTSD significantly influences glycemic, inflammatory, oxidant, and antioxidant parameters, as evidenced by increased levels of FSG, HbA1C, CRP, PC, MDA, 8-OHdG, and CP, as well as increased CAT activity and a reduced GSH concentration in the PTSD group in comparison to the external control group. Additionally, our results suggest that the environmental context in IDP camps by itself can potentially affect oxidant and antioxidant parameters, as evidenced by the increased concentrations of 8-OHdG, MDA, and PC and increased CAT activity found in individuals not diagnosed with PTSD but living inside the camps.

Genome-wide DNA methylation analysis in female veterans with military sexual trauma and comorbid PTSD/MDD

BackgroundMilitary sexual trauma (MST) is a prevalent issue within the U.S. military. Victims are more likely to develop comorbid diseases such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Nonetheless, not everyone who suffers from MST develops PTSD and/or MDD. DNA methylation, which can regulate gene expression, might give us insight into the molecular mechanisms behind this discrepancy. Therefore, we sought to identify genomic loci and enriched biological pathways that differ between patients with and without MST, PTSD, and MDD. MethodsSaliva samples were collected from 113 female veterans. Following DNA extraction and processing, DNA methylation levels were measured through the Infinium HumanMethylationEPIC BeadChip array. We used limma and bump hunting methods to generate the differentially methylated positions and differentially methylated regions (DMRs), respectively. Concurrently, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome to find enriched pathways. ResultsA DMR close to the transcription start site of ZFP57 was differentially methylated between subjects with and without PTSD, replicating previous findings and emphasizing the potential role of ZFP57 in PTSD susceptibility. In the pathway analyses, none survived multiple correction, although top GO terms included some potentially relevant to MST, PTSD, and MDD etiology. ConclusionWe conducted one of the first DNA methylation analyses investigating MST along with PTSD and MDD. In addition, we found one DMR near ZFP57 to be associated with PTSD. The replication of this finding indicates further investigation of ZFP57 in PTSD may be warranted.

Psychosocial etiology of post-traumatic stress disorder caused by war trauma among Iran–Iraq war immigrants in Mehran, Iran

BackgroundPost-traumatic stress disorder (PTSD) is one of the most important and common disorders caused by war trauma. The aim of this study was to determine the relationship between psychosocial factors and PTSD in war-torn immigrants in Mehran, Iran. MethodThe present study was conducted by descriptive and correlational method. The data were collected from 245 people (121 women and 124 men) from war-torn immigrants 45 years and older who migrated from Mehran to Ilam during the Iran–Iraq war. The measuring tools were as follows: Post Traumatic Stress Disorder Scale, Multidimensional Scale of Perceived Social Support (MDPSS), Coping Strategies Scale (CSS-R), Multidimensional Health Locus of Control scale. ResultsThe prevalence rate of PTSD among war-torn immigrants in Mehran was 35.1 %. A significant negative correlation was observed between perceived social support and PTSD (p < .01). Coping strategies, including seeking social support, reappraisal/adaptation, problem-focused coping, and active coping, all showed significant negative correlations with PTSD (p < .01). Conversely, a significant positive correlation was found between avoidance coping strategies and self-control and PTSD (p < .01). In addition, there was a significant positive correlation between the external locus of control (believing in chance) and PTSD (P < 0.01) and significant negative correlation between internal locus of control and PTSD (P < .01). ConclusionWeakness in social support, locus of control and also inappropriate coping strategies against war trauma were among the strong risk factors for PTSD. Therefore, social and behavioral interventions are recommended to increase social support, teaching problem-solving skills and strengthen individual control among war-torn immigrants to reduce the risk of developing PTSD.

Interaction between PTSD-PRS and trauma affects PTSD likelihood in women victims of sexual assault.

Post-traumatic stress disorder (PTSD) is triggered by traumatic events, but genetic vulnerability and a history of childhood trauma are additional factors that may increase the risk of PTSD. Thus, our study focused on exploring the interaction between genetic susceptibility, as assessed by polygenic risk score (PRS), and traumatic events. We evaluated 68 women with PTSD who had been sexually assaulted and 63 healthy controls without a history of sexual assault. DNA was genotyped using the Infinium Global Screening Array (Illumina), and PRS analysis was performed using PRSice. Furthermore, logistic regression models were employed to examine the interaction between childhood trauma, traumatic life events, and PTSD-PRS and how they contribute to the risk of developing PTSD. We found a significant association between PRS, childhood trauma (p = 0.03; OR = 1.241), and PTSD. Additionally, an interaction was observed between PRS, traumatic life events, and childhood trauma, particularly relating to physical and emotional neglect (p = 0.028; OR = 1.010). When examining neglect separately, we found a modest association between emotional neglect and PTSD (p = 0.014; OR = 1.086). Our findings highlight the importance of considering genetic vulnerability and traumatic experiences in understanding the etiology of PTSD.

Blue Wavelength Light Treatment for Improving Sleep in Patients with Post-Traumatic Stress Disorder

Traumatic live events comprise the etiology of post-traumatic stress disorder (PTSD). PTSD patients are known to face adverse impacts on their mental and physical health. Symptoms of concern relating to PTSD include heightened anxiety levels, intrusive memories, nightmares, and problems with sleeping. Disrupted sleep leads to exhausted brain function that impedes the daily activities of individuals and impacts their perceived quality of life. Therefore, researchers have sought to examine interventions that help improve sleep and circadian rhythms. Recently, blue-light therapy has been the target of clinical research to understand its role in alleviating PTSD symptoms. Results from clinical trials showed that patients receiving blue light showed significant reductions in daytime sleepiness and fatigue. Furthermore, these individuals showed faster reaction times and greater phase advances in circadian rhythms, leading to earlier sleep onset at night. As we work towards focusing our attention on addressing mental health issues, investigating the benefits of non-pharmacological interventions such as blue-light therapy can help improve the health outcomes of PTSD patients.

Childhood Trauma and PTSD Symptoms: Disentangling the Roles of Emotion Regulation and Distress Tolerance.

Research documents that a history of childhood trauma increases risk for post-traumatic stress disorder (PTSD), greater emotion regulation difficulties (ERD), and reduced distress tolerance (DT). Independent lines of research implicate ERD and DT as transdiagnostic risk factors and link them to PTSD. To elucidate how such mechanisms may influence the etiology, maintenance, and treatment of PTSD, the current study investigates the distinct mediating roles of emotion regulation and DT, exploring which explains a larger indirect effect from childhood trauma to PTSD symptom severity. Participants (N = 385, aged 18-48) who endorsed a history of childhood trauma provided retrospective report of cumulative childhood trauma exposure, and of current ERD, DT, and PTSD symptom severity. Single and dual mediation analyses were used to assess indirect effects through ERD and DT in the relation between cumulative childhood trauma exposure and current PTSD symptom severity. ERD and DT were significantly and inversely related. Higher current self-ratings of PTSD symptom severity were explained by cumulative childhood trauma through ERD (B = 0.93, p < 0.001) and DT (B = 0.50, p < 0.05). The full model explained 36% of the variance in PTSD symptom severity. Current findings provide preliminary evidence of DT and emotion regulation (with specific facets identified) as distinct mechanisms in the development of PTSD. Of clinical relevance, current findings support post-trauma processing theories that contend individuals' recovery requires accepting and learning to modulate trauma-related emotional states. Implications for methods of treatment and prevention are discussed.

Metabolic and immune dysfunctions in post-traumatic stress disorder: what can we learn from animal models?

Highly stressful experiences such as terrorist attacks, domestic and sexual violence may lead to persistent pathological symptoms such as those seen in posttraumatic stress disorder (PTSD). There is growing evidence of multiple metabolic and immune disorders underlying the etiology and maintenance of PTSD. However, changes in the functioning of various systems and organs associated with PTSD are not well understood. Studies of reliable animal models is one of the effective scientific tools that can be used to gain insight into the role of metabolism and immunity in the comorbidity associated with PTSD. Since much progress has been made using animal models to understand mechanisms of PTSD, we summarized metabolic and immune dysfunction in mice and humans to compare certain outcomes associated with PTSD. The systemic effects of PTSD include chronic activation of the sympathetic nervous system (psycho-emotional stress), that leads to impairment of the function of the immune system, increased release of stress hormones, and metabolic changes. We discuss PTSD as a multisystem disease with its neurological, immunological, and metabolic components.

The influence of sleep on fear extinction in trauma-related disorders

In Posttraumatic Stress Disorder (PTSD), fear and anxiety become dysregulated following psychologically traumatic events. Regulation of fear and anxiety involves both high-level cognitive processes such as cognitive reattribution and low-level, partially automatic memory processes such as fear extinction, safety learning and habituation. These latter processes are believed to be deficient in PTSD. While insomnia and nightmares are characteristic symptoms of existing PTSD, abundant recent evidence suggests that sleep disruption prior to and acute sleep disturbance following traumatic events both can predispose an individual to develop PTSD. Sleep promotes consolidation in multiple memory systems and is believed to also do so for low-level emotion-regulatory memory processes. Consequently sleep disruption may contribute to the etiology of PTSD by interfering with consolidation in low-level emotion-regulatory memory systems. During the first weeks following a traumatic event, when in the course of everyday life resilient individuals begin to acquire and consolidate these low-level emotion-regulatory memories, those who will develop PTSD symptoms may fail to do so. This deficit may, in part, result from alterations of sleep that interfere with their consolidation, such as REM fragmentation, that have also been found to presage later PTSD symptoms. Here, sleep disruption in PTSD as well as fear extinction, safety learning and habituation and their known alterations in PTSD are first briefly reviewed. Then neural processes that occur during the early post-trauma period that might impede low-level emotion regulatory processes through alterations of sleep quality and physiology will be considered. Lastly, recent neuroimaging evidence from a fear conditioning and extinction paradigm in patient groups and their controls will be considered along with one possible neural process that may contribute to a vulnerability to PTSD following trauma.

Prospective longitudinal assessment of sensorimotor gating as a risk/resiliency factor for posttraumatic stress disorder.

Little is understood about cognitive mechanisms that confer risk and resiliency for posttraumatic stress disorder (PTSD). Prepulse Inhibition (PPI) is a measure of pre-attentional response inhibition that is a stable cognitive trait disrupted in many neuropsychiatric disorders characterized by poor behavioral or cognitive inhibition, including PTSD. Differentiating between PTSD-related phenotypes that are pre-existing factors vs. those that emerge specifically after trauma is critical to understanding PTSD etiology and can only be addressed by prospective studies. This study tested the hypothesis that sensorimotor gating performance is associated with risk/resiliency for combat-related PTSD. As part of a prospective, longitudinal study,1226active duty Marines and Navy Corpsman completed a PPI test as well as a clinical interview to assess PTSD symptoms both before, and 3 and 6 months after acombat deployment. Participants that developed PTSD 6 months following deployment (N=46) showed lower PPI across pre and post-deployment time pointscompared to participants who did not develop PTSD(N=1182) . Examination of the distribution of PTSD across PPI performance revealed a lower than expected number of cases in the highest performing quartile compared to the rest of the distribution (p < 0.04). When controlling for other factors that predict PTSD in this population, those in the top 25% of PPI performance showed a >50% reduction in chance to develop PTSD (OR = 0.32). Baseline startle reactivity and startle habituation were not significantly different between PTSD risk and control groups. These findings suggest that robust sensorimotor gating may represent a resiliency factor for development of PTSD following trauma.

Elucidating the Neurobiologic Etiology of Comorbid PTSD and Substance Use Disorders.

Early childhood maltreatment and other traumatic event experiences (“trauma”) are common among youth, including those with substance use problems including substance use disorders (SUD). Particularly, interpersonal violence is associated with high rates of comorbidity between posttraumatic stress disorder (PTSD) and SUD, and these comorbid disorders exhibit high levels of overlapping symptomatology. Theoretical models proposed to explain the bidirectional relationship between PTSD and SUD include the self-medication hypothesis and susceptibility hypothesis. In this article, we explore neurobiologic changes associated with trauma, PTSD, and SUD that underly dysregulated stress response. Examining lessons learned from recent translational and clinical research, we propose that further elucidating the neurobiologic etiology of comorbid PTSD and SUD will require a collaborative, interdisciplinary approach, including the integration of preclinical and clinical studies, exploration of biologic markers in clinical studies, and accumulation of larger studies and longitudinal studies with the power to study PTSD and SUD. Such research can transform the field and ultimately reduce high rates and costly impairment of co-occurring PTSD and SUD across the lifespan.

Deficiency of Tet3 in nucleus accumbens enhances fear generalization and anxiety-like behaviors in mice.

Stress-induced neuroepigenetic programming gains growing more and more interest in the studies of the etiology of posttraumatic stress disorder (PTSD). However, seldom attention is focused on DNA demethylation in fear memory generalization, which is the core characteristic of PTSD. Here, we show that ten-eleven translocation protein 3 (TET3), the most abundant DNA demethylation enzyme of the TET family in neurons, senses environmental stress and bridges neuroplasticity with behavioral adaptation during fear generalization. Foot shock strength dependently induces fear generalization and TET3 expression in nucleus accumbens (NAc) in mice. Inhibition of DNA demethylation by infusing demethyltransferase inhibitors or AAV-Tet3-shRNA virus in NAc enhances the fear generalization and anxiety-like behavior. Furthermore, TET3 knockdown impairs the dendritic spine density, PSD length, and thickness of neurons, decreases DNA hydroxymethylation (5hmC), reduces the expression of synaptic plasticity-related genes including Homer1, Cdkn1a, Cdh8, Vamp8, Reln, Bdnf, while surprisingly increases immune-related genes Stat1, B2m, H2-Q7, H2-M2, C3, Cd68 shown by RNA-seq. Notably, knockdown of TET3 in NAc activates microglia and CD39-P2Y12R signaling pathway, and inhibition of CD39 reverses the effects of TET3 knockdown on the fear memory generalization and anxiety. Overexpression of TET3 by Crispr-dSaCas9 virus delivery to activate endogenous Tet3 in NAc increases dendritic spine density of neurons in NAc and reverses fear memory generalization and anxiety-like behavior in mice. These results suggest that TET3 modulates fear generalization and anxiety via regulating synaptic plasticity and CD39 signaling pathway.

Insecure Adult Attachment Style and PTSD Symptom Severity among Firefighters: The Role of Distress Tolerance

ABSTRACT Trauma exposure and posttraumatic stress disorder (PTSD) symptoms among firefighters are prevalent and well-documented. Insecure adult attachment style (AAS) and distress tolerance (DT) present two factors with demonstrated relevance to the etiology and maintenance of PTSD. Few studies have examined these constructs in relation to PTSD symptomatology among firefighter populations. The present investigation examined the indirect effect of insecure romantic AAS (i.e., anxious AAS, avoidant AAS) on PTSD symptom severity through DT among firefighters. Exploratory analyses examined this model with each of the PTSD symptom clusters as outcomes. The sample was comprised of 105 firefighters (Mage = 40.43, SD = 9.15, 95.2% male) recruited from various departments in the southern U.S. An indirect effect was calculated using 10,000 bootstrapped samples. Indirect effects models in the primary analyses were significant when both anxious AAS (β = .20, SE = .10, CI = .06-.43) and avoidant AAS (β = .28, SE = .12, CI = .08-.54) were evaluated as predictors. Effects were evident after accounting for gender, relationship status, years of fire service, and trauma load (i.e., number of potentially traumatic event types experienced). Exploratory analyses revealed that anxious and avoidant AAS are both indirectly related to the PTSD intrusion, negative alterations in cognitions and mood, and alterations in arousal and reactivity symptom clusters through DT. Anxious AAS also demonstrated an indirect association with PTSD avoidance symptoms through DT. Attachment styles may influence PTSD symptoms among firefighters through a firefighter’s perceived ability to withstand emotional distress. This line of inquiry has potential to inform specialized intervention programs for firefighters. Clinical and empirical implications are discussed.

Central and Peripheral Immune Dysregulation in Posttraumatic Stress Disorder: Convergent Multi-Omics Evidence.

Posttraumatic stress disorder (PTSD) is a chronic and multifactorial disorder with a prevalence ranging between 6–10% in the general population and ~35% in individuals with high lifetime trauma exposure. Growing evidence indicates that the immune system may contribute to the etiology of PTSD, suggesting the inflammatory dysregulation as a hallmark feature of PTSD. However, the potential interplay between the central and peripheral immune system, as well as the biological mechanisms underlying this dysregulation remain poorly understood. The activation of the HPA axis after trauma exposure and the subsequent activation of the inflammatory system mediated by glucocorticoids is the most common mechanism that orchestrates an exacerbated immunological response in PTSD. Recent high-throughput analyses in peripheral and brain tissue from both humans with and animal models of PTSD have found that changes in gene regulation via epigenetic alterations may participate in the impaired inflammatory signaling in PTSD. The goal of this review is to assess the role of the inflammatory system in PTSD across tissue and species, with a particular focus on the genomics, transcriptomics, epigenomics, and proteomics domains. We conducted an integrative multi-omics approach identifying TNF (Tumor Necrosis Factor) signaling, interleukins, chemokines, Toll-like receptors and glucocorticoids among the common dysregulated pathways in both central and peripheral immune systems in PTSD and propose potential novel drug targets for PTSD treatment.

Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans

Posttraumatic stress disorder (PTSD) is a chronic and disabling psychiatric disorder prevalent in military veterans. Epigenetic mechanisms have been implicated in the etiology of PTSD, with DNA methylation being the most studied to identify novel molecular biomarkers associated with this disorder. We performed one of the largest single-sample epigenome-wide association studies (EWAS) of PTSD to date. Our sample included 1135 male European–American U.S. veterans who participated in the National Health and Resilience in Veterans Study (NHRVS). DNA was collected from saliva samples and the Illumina HumanMethylation EPIC BeadChip was used for the methylation analysis. PTSD was assessed using the PTSD Checklist. An EWAS was conducted using linear regression adjusted for age, cell-type proportions, first 10 principal components, and smoking status. After Bonferroni correction, we identified six genome-wide significant (GWS) CpG sites associated with past-month PTSD and three CpGs with lifetime PTSD (prange = 10−10–10−8). These CpG sites map to genes involved in immune function, transcription regulation, axonal guidance, cell signaling, and protein binding. Among these, SENP7, which is involved in transcription regulation and has been linked to risk-taking behavior and alcohol consumption in genome-wide association studies, replicated in an independent veteran cohort and was downregulated in medial orbitofrontal cortex of PTSD postmortem brain tissue. These findings suggest potential epigenetic biomarkers of PTSD that may help inform the pathophysiology of this disorder in veterans and other trauma-affected populations.

Volumetrijska analiza hipokampusne formacije i amigdaloidnog kompleksa u animalnom modelu posttraumatskog stresnog poremećaja

Introduction: Posttraumatic stress disorder (PTSD) represents a mental disorder that occurs after life threatening situations. Animal models in psychiatry studies represent a base from which results and conclusions can be translated to human population. Amygdala and hippocampus are important neuroanatomical substrates possibly relevant to PTSD pathogenesis. Aim: The aim of study was to investigate volumetric changes that occur in hippocampus and amygdala related to PTSD animal model. Material and methods: Experiment was conducted on adult male Wistar rats. They were two groups, experimental and control. Experimental paradigm lasted for 31 days during which animals were exposed to acute and chronic stress. Acute stress was performed on the first day and ten days later. In between, animals were exposed to chronic social stress by pair rotations. Before second acute stress exposure, experimental group was divided in two subgroups from which one received dexamethasone dose. After the experiment ended, animals were sacrificed and the brain was extracted. Following the freezing process, brain tissue samples were cut and prepared for microscopy using. This was followed by volumetric analysis of hippocampus and amygdala. Measurements were performed bilaterally using Image Tool 3.0 Software. Results: Results showed volumetric changes in these structures. Hippocampus had smaller volume in the experimental subgroup without dexamethasone (x̄ = 0.6144) compared to the control group (x̄ = 0.9688). Amygdala, as well, had smaller volumes in same subgroup compared to the control (x̄ = 10.0156 compared to x̄ = 11.5041). Conclusion: Our study provided results in agreement with several previous studies on rodents and contributes to the assumption that hippocampus and amygdala have significance in PTSD etiology. Further goal is to expand our study which will help us to better understand the disorder itself.

Novel Analysis Identifying Functional Connectivity Patterns Associated with Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder that can result from experiencing traumatic events. Accurate diagnosis and optimal treatment strategies can be difficult to achieve, due to the heterogeneous etiology and symptomology of PTSD, and overlap with other psychiatric disorders. Advancing our understanding of PTSD pathophysiology is therefore critical. While functional connectivity alterations have shown promise for elucidating the neurobiological mechanisms of PTSD, previous findings have been inconsistent. Eleven patients with PTSD in our first cohort (PTSD-A) and 11 trauma-exposed controls (TEC) underwent functional magnetic resonance imaging. First, we investigated the intrinsic connectivity within known resting state networks (eg, default mode, salience, and central executive networks) previously implicated in functional abnormalities with PTSD symptoms. Second, the overall topology of network structure was compared between PTSD-A and TEC using graph theory. Finally, we used a novel combination of graph theory analysis and scaled subprofile modeling (SSM) to identify a disease-related, covarying pattern of brain network organization. No significant group differences were found in intrinsic connectivity of known resting state networks and graph theory metrics (clustering coefficients, characteristic path length, smallworldness, global and local efficiencies, and degree centrality). The graph theory/SSM analysis revealed a topographical pattern of altered degree centrality differentiating PTSD-A from TEC. This PTSD-related network pattern expression was additionally investigated in a separate cohort of 33 subjects who were scanned with a different MRI scanner (22 patients with PTSD or PTSD-B, and 11 healthy trauma-naïve controls or TNC). Across all participant groups, pattern expression scores were significantly lower in the TEC group, while PTSD-A, PTSD-B, and TNC subject profiles did not differ from each other. Expression level of the pattern was correlated with symptom severity in the PTSD-B group. This method offers potential in developing objective biomarkers associated with PTSD. Possible interpretations and clinical implications will be discussed.

Association of Lipid Peroxidation Product 4-Hydroxynonenal with Post-Traumatic Stress Disorder.

Repeated activation of the hypothalamic-pituitary-adrenal axis system, sleep disturbances, and other symptoms related to posttraumatic stress disorder (PTSD) elevate reactive oxygen species, increase inflammation, and accelerate cellular aging, leading to neuroprogression and cognitive decline. However, there is no information about possible involvement of 4-hydroxynonenal (4-HNE), the product of lipid peroxidation associated with stress-associated diseases, in the complex etiology of PTSD. Therefore, the aim of this study was to compare the plasma levels of 4-HNE between war veterans with PTSD (n = 62) and age-, sex- and ethnicity- matched healthy control subjects (n = 58) in order to evaluate the potential of HNE-modified proteins as blood-based biomarker of PTSD. The genuine 4-HNE-Enzyme-Linked Immunosorbent Assay (HNE-ELISA), based on monoclonal antibody specific for HNE-histidine (HNE-His) adducts, was used to determine plasma HNE-protein conjugates. Our results revealed significantly elevated levels of 4-HNE in patients with PTSD. Moreover, the accumulation of plasma 4-HNE seems to increase with aging but in a negative correlation with BMI, showing specific pattern of change for individuals diagnosed with PTSD. These findings suggest that oxidative stress and altered lipid metabolism reflected by increase of 4-HNE might be associated with PTSD. If confirmed with further studies, elevated 4-HNE plasma levels might serve as a potential biomarker of PTSD.

A network analysis of two conceptual approaches to the etiology of PTSD

Two prominent conceptual models of posttraumatic stress disorder (PTSD) are the cognitive model, associated with cognitive processing therapy (CPT; Resick & Schnicke, 1992), and the functional contextualist model, underlying acceptance and commitment therapy (ACT; Hayes et al., 1999). Network analysis was used to examine dynamic interactions among cognitive (relating to CPT) and functional contextualistic (relating to ACT) variables and PTSD symptoms in a sample of 722 trauma-exposed adults. Results from the cognitive networks highlighted the importance of maladaptive beliefs about threat in maintaining the co-occurrence of PTSD symptoms and cognitive variables. Additionally, PTSD symptoms were more likely to lead to cognitive variables, rather than the reverse direction. Results from the functional contextualist networks identified numerous associations amongst variables that contribute to the co-occurrence of PTSD symptoms and psychological inflexibility. Findings from this study may help generate causal hypotheses that can be tested further using a longitudinal study design.

Gene Expression Differences Between Young Adults Based on Trauma History and Post-traumatic Stress Disorder.

Background: The purpose of this study was to identify gene expression differences associated with post-traumatic stress disorder (PTSD) and trauma exposure (TE) in a three-group study design comprised of those with and without trauma exposure and PTSD.Methods: We conducted gene expression and gene network analyses in a sample (n = 45) composed of female subjects of European Ancestry (EA) with PTSD, TE without PTSD, and controls.Results: We identified 283 genes differentially expressed between PTSD-TE groups. In an independent sample of Veterans (n = 78) a small minority of these genes were also differentially expressed. We identified 7 gene network modules significantly associated with PTSD and TE (Bonferroni corrected p ≤ 0.05), which at a false discovery rate (FDR) of q ≤ 0.2, were significantly enriched for biological pathways involved in focal adhesion, neuroactive ligand receptor interaction, and immune related processes among others.Conclusions: This study uses gene network analyses to identify significant gene modules associated with PTSD, TE, and controls. On an individual gene level, we identified a large number of differentially expressed genes between PTSD-TE groups, a minority of which were also differentially expressed in the independent sample. We also demonstrate a lack of network module preservation between PTSD and TE, suggesting that the molecular signature of PTSD and trauma are likely independent of each other. Our results provide a basis for the identification of likely disease pathways and biomarkers involved in the etiology of PTSD.