Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial.

ABSTRACT: This study tested the efficacy of repeated intravenous ketamine doses to reduce symptoms of posttraumatic stress disorder (PTSD). Veterans and service members with PTSD (n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS). There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability. This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of ketamine in PTSD treatment. ClinicalTrials.gov identifier: NCT02655692.

SUBMITTER: Abdallah CG

PROVIDER: S-EPMC8767037 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Circulating miRNA Associated with Posttraumatic Stress Disorder in a Cohort of Military Combat Veterans

Project description:Objective: Posttraumatic stress disorder (PTSD) affects a high proportion of returning combat veterans, but the biological mechanisms of PTSD remain unclear. Circulating micro RNAs (miRNAs) have been associated with depression, and anxiety disorders, but there is little understanding of how miRNAs may relate to PTSD. In this study we compare profiles of circulating miRNA in combat veterans with and without PTSD in order to better understand biological mechanisms of PTSD. Methods: Blood from 24 male military service members was collected following deployment to Operation Iraqi Freedom (OIF) or Operation Enduring Freedom (OEF), and subjects were assessed for PTSD symptoms using the PTSD checklist-military version. miRNA was isolated from whole blood and sequenced on the Ion Torrent PGM™ using the Ion 316 Chip v2. Differences in miRNA expression was compared between subjects with PTSD (N=15) and combat matched controls without PTSD (N=9). Significantly different miRNA, according to a FDR≤0.05, were assessed for predictive putative targets, and pathway analysis of related targets was completed. Results: PTSD was associated with 4 upregulated and 4 downregulated miRNA, including a 2.94 fold increase in miR-19a-3p and a 1.56 fold decrease in miR-15b. Pathway analysis show that PTSD is related to the axon guidance and Wnt signaling pathways, which work together along with the adherens junction and MAPK signaling pathways to support neuronal development through regulation of growth cones. The PTSD associated miRNAs related to transcription factors, including Transcription factor 7 (T-cell specific, HMG-box), Transcription factor 7 like 1, and Transcription factor 7 like 2. Conclusions: PTSD is associated with miRNAs that regulate biological functions that include neuronal activities, suggesting that they play a role in PTSD symptomatology.

2017-03-07 | GSE87768 | GEO

Evening-type military veterans report worse lifetime posttraumatic stress symptoms and greater brainstem activity across wakefulness and REM sleep.

Project description:Evening chronotypes exhibit increased rates of affective dyregulation and sleep disturbances (e.g., insomnia and nightmares). Such symptoms are common to military veterans with posttraumatic stress disorder (PTSD); however, the influence of chronotype on this population remains unknown. We examined behavioral, psychological, and neural correlates of chronotype in 36 combat-exposed military veterans with varying degrees of posttraumatic stress symptomatology. We employed FDG-PET to assess neural activity across wakefulness and rapid eye movement (REM) sleep. We used polysomnography and diaries to monitor sleep, and a self-report survey to measure chronotype. Eveningness was associated with greater lifetime PTSD symptoms, more disturbed sleep, and more frequent and intense nightmares. Eveningness was also associated with greater brain activity in posterior cingulate/precuneus and brainstem regions across wakefulness and REM sleep, overlapping with regions related to arousal and REM sleep generation. Chronotype may be an important correlate of neural activity in REM sleep-generating and/or arousal regulatory regions among combat-exposed veterans with PTSD symptoms. Further investigations of the role of chronotype in PTSD are warranted.

| S-EPMC3797161 | biostudies-literature

Apolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress symptoms in U.S. military veterans: Results from the National Health and Resilience in Veterans Study.

Project description:BACKGROUND:Previous research examining the association between apolipoprotein E (APOE) gene polymorphism and risk for posttraumatic stress disorder (PTSD) has been inconsistent due to the use of small and select samples. This study examined the relation between APOE genotype and PTSD symptoms in two nationally representative samples of U.S. military veterans. The potential effect of cumulative trauma burden and social support in moderating this association was also evaluated. METHODS:The main sample consisted of 1,386 trauma-exposed European American (EA) veterans (mean age: 62-63 years) who participated in the National Health and Resilience in Veterans Study (NHRVS) in 2011. The independent replication sample consisted of 509 trauma-exposed EA veterans from the 2013 NHRVS. RESULTS:APOE ?4 allele carriers reported significantly greater severity of PTSD symptoms than noncarriers in the main, but not the replication, sample. In both samples, the interaction of APOE ?4 carrier status and cumulative trauma burden was associated with greater severity of PTSD symptoms (F range = 2.53-8.09, all P's < .01), particularly re-experiencing/intrusion symptoms (F range = 3.59-4.24, P's < .001). Greater social support was associated with lower severity of PTSD symptoms among APOE ?4 allele carriers with greater cumulative trauma burden (? range -.27 to -.60, P's < .05). CONCLUSION:U.S. military veterans who are APOE ?4 allele carriers and exposed to a high number of traumas may be at increased risk for developing PTSD symptoms than ?4 noncarriers. Greater social support may moderate this association, thereby highlighting the potential importance of social support promoting interventions in mitigating the effect of ?4 × cumulative trauma burden on PTSD risk.

| S-EPMC5794529 | biostudies-literature

Amygdala Nuclei Volume and Shape in Military Veterans With Posttraumatic Stress Disorder.

Project description:BackgroundThe amygdala is a subcortical structure involved in socioemotional and associative fear learning processes relevant for understanding the mechanisms of posttraumatic stress disorder (PTSD). Research in animals indicates that the amygdala is a heterogeneous structure in which the basolateral and centromedial divisions are susceptible to stress. While the amygdala complex is implicated in the pathophysiology of PTSD, little is known about the specific contributions of the individual nuclei that constitute the amygdala complex.MethodsMilitary veterans (n = 355), including military veterans with PTSD (n = 149) and trauma-exposed control subjects without PTSD (n = 206), underwent high-resolution T1-weighted anatomical scans. Automated FreeSurfer segmentation of the amygdala yielded 9 structures: basal, lateral, accessory basal, anterior amygdaloid, and central, medial, cortical, and paralaminar nuclei, along with the corticoamygdaloid transition zone. Subregional volumes were compared between groups using ordinary-least-squares regression with relevant demographic and clinical regressors followed by 3-dimensional shape analysis of whole amygdala.ResultsPTSD was associated with smaller left and right lateral and paralaminar nuclei, but with larger left and right central, medial, and cortical nuclei (p < .05, false discovery rate corrected). Shape analyses revealed lower radial distance in anterior bilateral amygdala and lower Jacobian determinant in posterior bilateral amygdala in PTSD compared with control subjects.ConclusionsAlterations in select amygdala subnuclear volumes and regional shape distortions are associated with PTSD in military veterans. Volume differences of the lateral nucleus and the centromedial complex associated with PTSD demonstrate a subregion-specific pattern that is consistent with their functional roles in fear learning and fear expression behaviors.

| S-EPMC8040290 | biostudies-literature

Circulating miRNA associated with posttraumatic stress disorder in a cohort of military combat veterans.

Project description:Posttraumatic stress disorder (PTSD) affects many returning combat veterans, but underlying biological mechanisms remain unclear. In order to compare circulating micro RNA (miRNA) of combat veterans with and without PTSD, peripheral blood from 24 subjects was collected following deployment, and isolated miRNA was sequenced. PTSD was associated with 8 differentially expressed miRNA. Pathway analysis shows that PTSD is related to the axon guidance and Wnt signaling pathways, which work together to support neuronal development through regulation of growth cones. PTSD is associated with miRNAs that regulate biological functions including neuronal activities, suggesting that they play a role in PTSD symptomatology.

| S-EPMC6065100 | biostudies-literature

Posttraumatic Stress Disorder and Justice Involvement Among Military Veterans: A Systematic Review and Meta-Analysis.

Project description:There is evidence of an association between posttraumatic stress disorder (PTSD) and criminal justice involvement among military veterans. For this study, we systematically reviewed the literature to examine the association between PTSD and criminal justice involvement among military veterans, assess the magnitude of this association, and identify strengths and limitations of the underlying evidence. Five databases were searched for a larger scoping review, and observational studies that assessed PTSD and criminal justice involvement were selected from the scoping review database (N = 191). Meta-analyses were conducted, pooling odds ratios (ORs) via restricted maximum likelihood random-effects models. The main outcomes were criminal justice involvement (i.e., documentation of arrest) and PTSD (i.e., PTSD assessment score indicating probable PTSD). Of 143 unique articles identified, 10 studies were eligible for the meta-analysis. Veterans with PTSD had higher odds of criminal justice involvement (OR = 1.61, 95% CI [1.16, 2.23], p = .002) and arrest for violent offenses (OR = 1.59, 95% CI [1.15, 2.19], p = .002) compared to veterans without PTSD. The odds ratio of criminal justice involvement among military veterans with PTSD assessed using the PTSD Checklist was 1.98, 95% CI [1.08, 3.63], p = .014. Considerable heterogeneity was identified, but no evidence of publication bias was found. Criminal justice involvement and PTSD are linked among military veterans, highlighting an important need for clinicians and healthcare systems working with this population to prioritize PTSD treatment to reduce veterans' new and recurring risk of criminal justice involvement.

| S-EPMC8288507 | biostudies-literature

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

Project description: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.

| S-EPMC8854688 | biostudies-literature

POSTTRAUMATIC STRESS SYMPTOMS AND AVERSION TO AMBIGUOUS LOSSES IN COMBAT VETERANS.

Project description:Psychiatric symptoms typically cut across traditional diagnostic categories. In order to devise individually tailored treatments, there is a need to identify the basic mechanisms that underlie these symptoms. Behavioral economics provides a framework for studying these mechanisms at the behavioral level. Here, we utilized this framework to examine a widely ignored aspect of trauma-related symptomatology-individual uncertainty attitudes-in combat veterans with and without posttraumatic stress disorder (PTSD).Fifty-seven combat veterans, including 30 with PTSD and 27 without PTSD, completed a risk and ambiguity decision-making task that characterizes individual uncertainty attitudes, distinguishing between attitudes toward uncertain outcomes with known ("risk") and unknown ("ambiguity") probabilities, and between attitudes toward uncertain gains and uncertain losses. Participants' choices were used to estimate risk and ambiguity attitudes in the gain and loss domains.Veterans with PTSD were more averse to ambiguity, but not risk, compared to veterans without PTSD, when making choices between possible losses, but not gains. The degree of aversion was associated with anxious arousal (e.g., hypervigilance) symptoms, as well as with the degree of combat exposure. Moreover, ambiguity attitudes fully mediated the association between combat exposure and anxious arousal symptoms.These results provide a foundation for prospective studies of the causal association between ambiguity attitudes and trauma-related symptoms, as well as etiologic studies of the neural underpinnings of these behavioral outcomes. More generally, these results demonstrate the potential of neuroeconomic and behavioral economic techniques for devising objective and incentive-compatible diagnostic tools, and investigating the etiology of psychiatric disorders.

| S-EPMC5247796 | biostudies-literature

The 20-year course of posttraumatic stress disorder symptoms among veterans.

Project description:Although numerous longitudinal studies have examined heterogeneity in posttraumatic stress disorder (PTSD) symptom course, the long-term course of the disorder remains poorly understood. This study sought to understand and predict long-term PTSD symptom course among a nationwide sample of Operations Enduring Freedom and Iraqi Freedom veterans enrolled in Veterans Health Administration services. We assessed PTSD symptoms at 4 time points over approximately 4.5 years (M = 55.11 months, SD = 6.89). Participants (N = 1,353) with and without probable PTSD were sampled at a 3:1 ratio, and male and female veterans were sampled at a 1:1 ratio to fully explore the heterogeneity of PTSD symptom course and the effect of sex on symptom course. By coding time as years since index trauma, we estimated the course of PTSD symptoms over 20 years. Results indicate symptom course is most appropriately characterized by substantial heterogeneity. On average, veterans experienced initial PTSD symptom severity above the diagnostic threshold following trauma exposure, which was initially stable over time and later began to gradually improve. Although results indicate symptoms eventually began to decline, this effect was gradual; most participants continued to meet or exceed the PTSD provisional diagnostic threshold long after trauma exposure. We identified several predictors and correlates of symptom course, including Hispanic ethnicity, postdeployment social support, and co-occurring psychopathology. Results highlight the heterogeneous nature of PTSD symptom course following trauma exposure and the urgency of the need to ensure access to evidence-based care and to improve available treatments. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

| S-EPMC7416431 | biostudies-literature

Roles of Guilt Cognitions in Trauma-Related Sleep Disturbance in Military Veterans With Posttraumatic Stress Disorder.

Project description:Objective/Background: Despite a well-established role of guilt cognitions in the maintenance and treatment of posttraumatic stress disorder (PTSD), relationships of guilt cognitions to nightmares are not well understood. This study investigated the ways in which guilt cognitions, related to traumatic events, influenced the relationship between combat exposure and trauma-related sleep disturbance in military Veterans with PTSD. Participants: We recruited a sample of 50 Veterans with PTSD who completed study measures at a screening session. Methods: Participants completed self-report measures of exposure to potentially traumatic events, trauma-related guilt (hindsight bias, wrongdoing, and lack of justification) and trauma-related sleep disturbance as measured by a self-report scale and clinician ratings of nightmare severity. Results: Bivariate regression analyses established a relationship of combat exposure to wrongdoing (? = .31, p = .031), and a relationship of wrongdoing with self-reported trauma-related sleep disturbance (? = .27, p = .049) and clinician-rated nightmare severity (? = .36, p = .009). Bootstrapping analysis that included years of education as a covariate found a significant overall indirect effect of combat exposure on clinician-rated nightmare severity exerted through wrongdoing (? = .10, 95% CI [.004, .246]). Conclusions: Results suggest the association of combat exposure with trauma-related sleep disturbance is significantly influenced by perceived wrongdoing related to a traumatic event. Targeting cognitions related to wrongdoing and moral injury during a traumatic event in PTSD treatment may help ameliorate trauma-related sleep disturbance.

| S-EPMC6109613 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data