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.
Project description:ObjectiveIndividuals with posttraumatic stress disorder (PTSD) smoke at higher rates compared to the general population and experience significant barriers to initiating cessation treatment. Proactive outreach addresses these barriers by directly engaging with smokers and facilitating access to treatment. The objective of the present study was to evaluate a proactive outreach intervention for increasing rates of treatment utilization and abstinence among veteran smokers with and without PTSD.MethodThis is a secondary analysis of a randomized controlled trial conducted from 2013 to 2017 that demonstrated the effectiveness of proactive outreach among veterans using Veterans Affairs mental health care services. Electronic medical record data were used to identify participants with (n = 355) and without (n = 1,583) a diagnosis of PTSD. Logistic regressions modeled cessation treatment utilization (counseling, nicotine replacement therapy [NRT], and combination treatment) and abstinence (7-day point prevalence and 6-month prolonged at 6- and 12-month follow-ups) among participants randomized to proactive outreach versus usual care in the PTSD and non-PTSD subgroups, respectively.ResultsCompared to usual care, proactive outreach increased combined counseling and NRT utilization among participants with PTSD (odds ratio [OR] = 26.25, 95% confidence interval [3.43, 201.17]) and without PTSD (OR = 10.20, [5.21, 19.98]). Proactive outreach also increased 7-day point prevalence abstinence at 12 months among participants with PTSD (OR = 2.62, [1.16, 5.91]) and without PTSD (OR = 1.61, [1.11, 2.34]).ConclusionsProactive outreach increased treatment utilization and abstinence among smokers with and without PTSD. Smokers with PTSD may need additional facilitation to initiate cessation treatment but are receptive when it is offered proactively. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Project description:Posttraumatic stress disorder (PTSD) is a disabling disorder associated with resting state functional connectivity alterations. However, whether specific brain regions are altered in PTSD or whether the whole brain network organization differs remains unclear. PTSD can be treated with trauma-focused therapy, although only half of the patients recover after treatment. In order to better understand PTSD psychopathology our aim was to study resting state networks in PTSD before and after treatment. Resting state functional magnetic resonance images were obtained from veterans with PTSD (n = 50) and controls (combat and civilian controls; n = 54) to explore which network topology properties (degree and clustering coefficient) of which brain regions are associated with PTSD. Then, PTSD-associated brain regions were investigated before and after treatment. PTSD patients were subdivided in persistent (n = 22) and remitted PTSD patients (n = 17), and compared with combat controls (n = 22), who were also reassessed. Prior to treatment associations with PTSD were found for the degree of orbitofrontal, and temporoparietal brain regions, and for the clustering coefficient of the anterior cingulate cortex. No significant effects were found over the course of treatment. Our results are in line with previous resting state studies, showing resting state connectivity alterations in the salience network and default mode network in PTSD, and also highlight the importance of other brain regions. However, network metrics do not seem to change over the course of treatment. This study contributes to a better understanding of the psychopathology of PTSD.
Project description:BackgroundThe diagnosis of posttraumatic stress disorder (PTSD) is usually based on clinical interviews or self-report measures. Both approaches are subject to under- and over-reporting of symptoms. An objective test is lacking. We have developed a classifier of PTSD based on objective speech-marker features that discriminate PTSD cases from controls.MethodsSpeech samples were obtained from warzone-exposed veterans, 52 cases with PTSD and 77 controls, assessed with the Clinician-Administered PTSD Scale. Individuals with major depressive disorder (MDD) were excluded. Audio recordings of clinical interviews were used to obtain 40,526 speech features which were input to a random forest (RF) algorithm.ResultsThe selected RF used 18 speech features and the receiver operating characteristic curve had an area under the curve (AUC) of 0.954. At a probability of PTSD cut point of 0.423, Youden's index was 0.787, and overall correct classification rate was 89.1%. The probability of PTSD was higher for markers that indicated slower, more monotonous speech, less change in tonality, and less activation. Depression symptoms, alcohol use disorder, and TBI did not meet statistical tests to be considered confounders.ConclusionsThis study demonstrates that a speech-based algorithm can objectively differentiate PTSD cases from controls. The RF classifier had a high AUC. Further validation in an independent sample and appraisal of the classifier to identify those with MDD only compared with those with PTSD comorbid with MDD is required.
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).
Project description:BackgroundCurrent research in behavioral cardiology reveals a significant association between posttraumatic stress disorder (PTSD) and increased risk for cardiovascular disease and mortality; however, the underlying mechanisms remain poorly understood. We hypothesized that patients with PTSD would exhibit endothelial dysfunction, a potential mechanism involved in the development and progression of cardiovascular disease.Methods and resultsA total of 214 outpatients treated at the San Francisco Veterans Affairs Medical Center underwent tests of endothelial function and evaluation for PTSD. Flow-mediated vasodilation of the brachial artery was performed to assess endothelial function, and current PTSD status was defined by the PTSD Checklist, based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), with a score ≥40. Multivariable linear regression models were used to estimate the association between PTSD status and endothelial function. Patients with PTSD (n=67) were more likely to be male (99% versus 91%, P=0.04) and to have depression (58% versus 8%, P<0.0001) and were less likely to be on an angiotensin-converting enzyme inhibitor (17% versus 36%, P=0.007) or β-blocker treatment (25% versus 41%, P=0.03). Univariate analysis demonstrated that patients with PTSD had significantly lower flow-mediated vasodilation (5.8±3.4% versus 7.5±3.7%; P=0.003); furthermore, lower flow-mediated vasodilation was associated with increasing age (P=0.008), decreasing estimated glomerular filtration rate (P=0.003), hypertension (P=0.002), aspirin (P=0.03), and β-blocker treatments (P=0.01). In multivariable analysis, PTSD remained independently associated with lower flow-mediated vasodilation (P=0.0005).ConclusionsAfter adjusting for demographic, comorbidity, and treatment characteristics, PTSD remained associated with worse endothelial function in an outpatient population. Whether poor endothelial function contributes to the higher risk of cardiovascular disease in patients with PTSD deserves further study.
Project description:Chronic Posttraumatic stress disorder (PTSD), characterized by symptoms of re-experiencing, hyperarousal, and avoidance, is challenging to treat as a significant proportion of patients remain symptomatic following even empirically supported interventions. The current case series investigated the effects of up to 10 sessions of high definition transcranial direct current stimulation (HD-tDCS) on symptoms of PTSD. Participants received HD-tDCS that targeted the right lateral temporal cortex (LTC; center cathode placed over T8), given this region's potential involvement in symptoms of re-experiencing and, possibly, hyperarousal. Five of the six enrolled patients completed at least 8 sessions. Of these five, four showed improvement in symptoms of re-experiencing after HD-tDCS. This improvement was accompanied by connectivity change in the right LTC as well as a larger extended fear network but not a control network that consisted of visual cortex regions; however, the nature of the change varied across participants as some showed increased connectivity whereas others showed decreased connectivity. These preliminary data suggest that HD-tDCS may be beneficial for treatment of specific PTSD symptoms, in at least some individuals, and warrants further investigation.
Project description:OBJECTIVE:This study's objective was to evaluate the effect of two common components of meditation (mindfulness and slow breathing) on potential mechanistic pathways. METHODS:A total of 102 combat veterans with posttraumatic stress disorder (PTSD) were randomized to (a) the body scan mindfulness meditation (MM), (b) slow breathing (SB) with a biofeedback device, (c) mindful awareness of the breath with an intention to slow the breath (MM+SB), or (d) sitting quietly (SQ). Participants had 6 weekly one-on-one sessions with 20 minutes of daily home practice. The mechanistic pathways and measures were as follows: (a) autonomic nervous system (hyperarousal symptoms, heart rate [HR], and heart rate variability [HRV]); (b) frontal cortex activity (attentional network task [ANT] conflict effect and event-related negativity and intrusive thoughts); and (c) hypothalamic-pituitary-adrenal axis (awakening cortisol). PTSD measures were also evaluated. RESULTS:Meditation participants had significant but modest within-group improvement in PTSD and related symptoms, although there were no effects between groups. Perceived impression of PTSD symptom improvement was greater in the meditation arms compared with controls. Resting respiration decreased in the meditation arms compared with SQ. For the mechanistic pathways, (a) subjective hyperarousal symptoms improved within-group (but not between groups) for MM, MM+SB, and SQ, while HR and HRV did not; (b) intrusive thoughts decreased in MM compared with MM+SB and SB, while the ANT measures did not change; and (c) MM had lower awakening cortisol within-group (but not between groups). CONCLUSION:Treatment effects were mostly specific to self-report rather than physiological measures. Continued research is needed to further evaluate mindfulness meditation's mechanism in people with PTSD.
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.
Project description:Posttraumatic stress disorder (PTSD) is a debilitating disorder that has been associated with brain abnormalities, including white matter alterations. However, little is known about the effect of treatment on these brain alterations. To investigate the course of white matter alterations in PTSD, we used a longitudinal design investigating treatment effects on white matter integrity using diffusion tensor imaging (DTI). Diffusion tensor and magnetization transfer images were obtained pre- and posttreatment from veterans with (n=39) and without PTSD (n=22). After treatment, 16 PTSD patients were remitted, and 23 had persistent PTSD based on PTSD diagnosis. The dorsal and hippocampal cingulum bundle, stria terminalis, and fornix were investigated as regions of interest. Exploratory whole-brain analyses were also performed. Groups were compared with repeated-measures ANOVA for fractional anisotropy (FA), and magnetization transfer ratio. Persistently symptomatic PTSD patients had increasing FA of the dorsal cingulum over time, and at reassessment these FA values were higher than both combat controls and the remitted PTSD group. Group-by-time interactions for FA were found in the hippocampal cingulum, fornix, and stria terminalis, posterior corona radiata, and superior longitudinal fasciculus. Our results indicate that higher FA of the dorsal cingulum bundle may be an acquired feature of persistent PTSD that develops over time. Furthermore, treatment might have differential effects on the hippocampal cingulum, fornix, stria terminalis, posterior corona radiata, and superior longitudinal fasciculus in remitted vs persistent PTSD patients. This study contributes to a better understanding of the neural underpinnings of PTSD treatment outcome.