Substance Use after Completion of an Intensive Treatment Program with Concurrent Treatment for Posttraumatic Stress Disorder and Substance Use among Veterans: Examining the Role of PTSD Symptoms.

OBJECTIVE: Substance use disorders (SUDs) and posttraumatic stress disorder (PTSD) are costly and highly co-occurring diagnoses, particularly among veterans, suggesting a need to understand this comorbidity and effectively treat both disorders among this population. METHODS: The current study aimed to examine substance use outcomes among post-9/11 veterans and service members (N = 48) who completed a two-week intensive outpatient program with concurrent treatment for and PTSD using Prolonged Exposure and substance use. Substance use was assessed at two weeks and three months posttreatment. RESULTS: The intensive program had high completion rates and demonstrated decreases in substance use at two weeks and three months posttreatment. Additionally, lower PTSD symptoms at treatment completion were related to less substance use posttreatment. CONCLUSIONS: Concurrent intensive treatment of PTSD and SUDs can lead to symptom improvement in a short period of time. Findings support the self-medication model, such that PTSD symptoms at treatment completion were related to substance use at follow-up.

The relations between C-reactive protein and trauma exposure, PTSD and depression symptoms, and PTSD psychotherapy treatment response in treatment seeking veterans and service members.

While inflammatory markers have been implicated in the link between PTSD and poor health outcomes, there is a paucity of research investigating C-reactive protein (CRP) and psychotherapy treatment response for posttraumatic stress disorder (PTSD). The present study utilized a large, well-characterized sample of veterans and service members (N = 493) engaged in intensive psychotherapy to investigate the associations between CRP, trauma exposure, related variables, and PTSD and depression, as well as investigating if CRP was associated with PTSD psychotherapy treatment response. Bivariate correlation results indicate that CRP was significantly associated with BMI (r = 0.48) and severity of experiences of childhood physical and sexual abuse (r = 0.14 and 0.15, respectively) and was not significantly associated with baseline PTSD total symptom severity, PTSD symptom clusters, or depression symptom severity (rs ranging from -0.03 to 0.04). In multivariate regression models investigating if CRP and related variables were associated with PTSD baseline symptom severity, CRP was not a significant predictor (ß = -0.03). Hierarchical linear modeling did not identify CRP as a significant predictor of PTSD psychotherapy outcome. Given that findings indicate that CRP was broadly elevated in this treatment seeking sample but not associated with PTSD and depression symptom severity, results suggest CRP may not be a specific biomarker for PTSD or depression but may be elevated in psychiatric disease more generally.

Integration of peripheral transcriptomics, genomics, and interactomics following trauma identifies causal genes for symptoms of post-traumatic stress and major depression.

Posttraumatic stress disorder (PTSD) is a debilitating syndrome with substantial morbidity and mortality that occurs in the aftermath of trauma. Symptoms of major depressive disorder (MDD) are also a frequent consequence of trauma exposure. Identifying novel risk markers in the immediate aftermath of trauma is a critical step for the identification of novel biological targets to understand mechanisms of pathophysiology and prevention, as well as the determination of patients most at risk who may benefit from immediate intervention. Our study utilizes a novel approach to computationally integrate blood-based transcriptomics, genomics, and interactomics to understand the development of risk vs. resilience in the months following trauma exposure. In a two-site longitudinal, observational prospective study, we assessed over 10,000 individuals and enrolled >700 subjects in the immediate aftermath of trauma (average 5.3 h post-trauma (range 0.5-12 h)) in the Grady Memorial Hospital (Atlanta) and Jackson Memorial Hospital (Miami) emergency departments. RNA expression data and 6-month follow-up data were available for 366 individuals, while genotype, transcriptome, and phenotype data were available for 297 patients. To maximize our power and understanding of genes and pathways that predict risk vs. resilience, we utilized a set-cover approach to capture fluctuations of gene expression of PTSD or depression-converting patients and non-converting trauma-exposed controls to find representative sets of disease-relevant dysregulated genes. We annotated such genes with their corresponding expression quantitative trait loci and applied a variant of a current flow algorithm to identify genes that potentially were causal for the observed dysregulation of disease genes involved in the development of depression and PTSD symptoms after trauma exposure. We obtained a final list of 11 driver causal genes related to MDD symptoms, 13 genes for PTSD symptoms, and 22 genes in PTSD and/or MDD. We observed that these individual or combined disorders shared ESR1, RUNX1, PPARA, and WWOX as driver causal genes, while other genes appeared to be causal driver in the PTSD only or MDD only cases. A number of these identified causal pathways have been previously implicated in the biology or genetics of PTSD and MDD, as well as in preclinical models of amygdala function and fear regulation. Our work provides a promising set of initial pathways that may underlie causal mechanisms in the development of PTSD or MDD in the aftermath of trauma.

The role of depression in the maintenance of gains after a prolonged exposure intensive outpatient program for posttraumatic stress disorder.

BACKGROUND: Intensive outpatient programs (IOPs) for trauma-focused therapy, such as prolonged exposure (PE), have the potential to deliver highly effective treatment, quickly and with minimal dropout. Identifying factors that predict maintenance of gains after treatment can help triage individuals who may need additional services. METHODS: Growth mixture modeling (GMM) was used to identify classes of posttraumatic stress disorder (PTSD) and depression symptom trajectories across the year following a 2-week IOP, delivering daily PE for PTSD for post-9/11 Veterans. Predictors of trajectories were examined. RESULTS: Three classes of trajectories best-fit the data for PTSD and depression symptoms. Two classes made up the majority of the sample (85%) and both maintained significantly reduced PTSD symptoms across the year following therapy. For a minority of the sample (14.6%), PTSD symptoms rebounded after treatment. These individuals were highly likely to be categorized in the persistent depression class. CONCLUSIONS: IOP-delivered PE is effective, and gains are largely maintained. The minority of patients who do not maintain their gains as robustly are likely to report persistent depressive symptoms in treatment and higher PTSD symptoms on a self-report measure.

Change in posttraumatic stress disorder-related thoughts during treatment: Do thoughts drive change when pills are involved?

Posttraumatic negative thoughts about one's self and the world are related to posttraumatic stress disorder (PTSD) symptom severity and change in cognitive behavioral treatment (CBT), but little is known about this association when CBT is delivered with medication. The current study presents a planned comparison of changes in negative posttraumatic thoughts during (a) prolonged exposure (PE) plus pill placebo (PE+PLB), (b) sertraline plus enhanced medication management (SERT+EMM), and (c) PE plus sertraline (PE+SERT) as part of a randomized clinical trial in a sample of 176 veterans. Lagged regression modeling revealed that change in posttraumatic negative thoughts was associated with PTSD symptom change in the conditions in which participants received sertraline, ds = 0.14-0.25, ps = 0.04-.001). However, contrary to previous research, the models that started with symptom change were also statistically significant, d = 0.23, p < .001, for the lagged effect of symptoms on negative thoughts about self in the SERT+EMM condition, indicating a bidirectional association between such thoughts and PTSD symptoms. In the PE+PLB condition, no significant association between posttraumatic thoughts and PTSD symptoms emerged in either direction. These results suggest that the previously demonstrated role of change in posttraumatic thoughts leading to PTSD symptom reduction in PE may be altered when combined with pill administration, either active or placebo.

Psychophysiology during exposure to trauma memories: Comparative effects of virtual reality and imaginal exposure for posttraumatic stress disorder.

BACKGROUND: This investigation involved an in-depth examination of psychophysiological responses during exposure to the trauma memory across 10 sessions among active duty soldiers with combat-related posttraumatic stress disorder (PTSD) treated by Prolonged Exposure (PE) or Virtual Reality Exposure (VRE). We compared psychophysiological changes, session-by-session, between VRE and traditional imaginal exposure. METHODS: Heart rate (HR), galvanic skin response (GSR), and peripheral skin temperature were collected every 5 min during exposure sessions with 61 combat veterans of Iraq/Afghanistan and compared to the PTSD Checklist (PCL-C) and Clinician-Administered PTSD Scale (CAPS) outcomes using multilevel modeling. RESULTS: Over the course of treatment, participants in the PE group had higher HR arousal compared to participants in the VRE group. With reference to GSR, in earlier sessions, participants demonstrated a within-session increase, whereas, in later sessions, participants showed a within-session habituation response. A significant interaction was found for GSR and treatment assignment for within-session change, within-person effect, predicting CAPS (d = 0.70) and PCL-C (d = 0.66) outcomes. CONCLUSION: Overall, these findings suggest that exposure to traumatic memories activates arousal across sessions, with GSR being most associated with reductions in PTSD symptoms for participants in the PE group.

Prior trauma-related experiences predict the development of posttraumatic stress disorder after a new traumatic event.

BACKGROUND: Many reports have documented the relationship between previous traumatic experiences, including childhood trauma, and the development of later life psychopathology, including posttraumatic stress disorder (PTSD). Identification of individuals at greatest risk for the development of PTSD could lead to preventative interventions. The present study examined the developmental course of PTSD after trauma exposure, using histories of previous traumatic experiences and the severity of the reaction to the trauma as predictors. METHODS: Participants (N = 713) were recruited from Emergency Departments in Miami and Atlanta immediately following a traumatic experience. Histories of previous traumatic experiences and the immediate reaction to the new trauma were examined at baseline. Follow-up assessments of PTSD severity were conducted at 1, 3, and 6 months. RESULTS: Histories of child abuse and pre-existing trauma symptoms predicted the immediate response to stress (R2 = .21, p < .001) and the initial trauma reaction (p < .005).) A mixed-model repeated-measures analysis of variance found that immediate stress response and a history of prior trauma (p < .001) significantly predicted the course of PTSD symptoms. Area under the curve (AUC) analyses suggested that the presence of PTSD at each successive assessment was predicted most substantially by the severity of PTSD at the immediately prior follow-up assessment (AUC > 0.86). CONCLUSIONS: The current findings suggest that previous traumatic experiences lead to a greater immediate reaction to trauma and combine to predict the development of PTSD, the maintenance of which is not moderated by these earlier experiences. The identification of people likely to develop PTSD may be aided by the assessment of prior experiences and immediate reactions.

Multimodal structural neuroimaging markers of risk and recovery from posttrauma anhedonia: A prospective investigation.

BACKGROUND: Anhedonic symptoms of posttraumatic stress disorder (PTSD) reflect deficits in reward processing that have significant functional consequences. Although recent evidence suggests that disrupted integrity of fronto-limbic circuitry is related to PTSD development, including anhedonic PTSD symptoms (posttrauma anhedonia [PTA]), little is known about potential structural biomarkers of long-term PTA as well as structural changes in fronto-limbic pathways associated with recovery from PTA over time. METHODS: We investigated associations between white matter microstructure, gray matter volume, and PTA in 75 recently traumatized individuals, with a subset of participants (n = 35) completing follow-up assessment 12 months after trauma exposure. Deterministic tractography and voxel-based morphometry were used to assess changes in white and gray matter structure associated with changes in PTA. RESULTS: Reduced fractional anisotropy (FA) of the uncinate fasciculus at around the time of trauma predicted greater PTA at 12-months posttrauma. Further, increased FA of the fornix over time was associated with lower PTA between 1 and 12-months posttrauma. Increased gray matter volume of the ventromedial prefrontal cortex and precuneus over time was also associated with reduced PTA. CONCLUSIONS: The microstructure of the uncinate fasciculus, an amygdala-prefrontal white matter connection, may represent a biomarker of vulnerability for later PTA. Conversely, development and recovery from PTA appear to be facilitated by white and gray matter structural changes in a major hippocampal pathway, the fornix. The present findings shed new light on neuroanatomical substrates of recovery from PTA and characterize white matter biomarkers of risk for posttraumatic dysfunction.

Integrating virtual realities and psychotherapy: SWOT analysis on VR and MR based treatments of anxiety and stress-related disorders.

The use of virtual reality (VR) and mixed reality (MR) technology in clinical psychology is growing. Efficacious VR-based treatments for a variety of disorders have been developed. However, the field of technology-assisted psychotherapy is constantly changing with the advancement in technology. Factors such as interdisciplinary collaboration, consumer familiarity and adoption of VR products, and progress in clinical science all need to be taken into consideration when integrating virtual technologies into psychotherapies. We aim to present an overview of current expert opinions on the use of virtual technologies in the treatment of anxiety and stress-related disorders. An anonymous survey was distributed to a select group of researchers and clinicians, using an analytic framework known as Strengths, Weaknesses, Opportunities, and Threats (SWOT). Overall, the respondents had an optimistic outlook regarding the current use as well as future development and implementation of technology-assisted interventions. VR and MR psychotherapies offer distinct advantages that can overcome shortcomings associated with traditional therapy. The respondents acknowledged and discussed current limitations of VR and MR psychotherapies. They recommended consolidation of existing knowledge and encouraged standardisation in both theory and practice. Continued research is needed to leverage the strengths of VR and MR to develop better treatments.Abbreviations: AR: Augmented Reality; MR: Mixed Reality; RCT: Randomised Controlled Trial; SWOT: Strengths, Weaknesses, Opportunities, and Threats; VR: Virtual Reality; VR-EBT: Virtual Reality Exposure-Based Therapy.

Eight weeks of device-guided slow breathing decreases sympathetic nervous reactivity to stress in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is characterized by increased risk for developing hypertension and cardiovascular disease. We recently showed that device-guided slow breathing (DGB) acutely lowers blood pressure (BP) and muscle sympathetic activity (MSNA) and improves baroreflex sensitivity (BRS) in PTSD. The aim of this study was to assess the long-term benefits of DGB on autonomic function at rest and during stress. We hypothesized that long-term DGB improves arterial BRS and lowers BP and MSNA in PTSD. Twenty-five veterans with PTSD were studied and randomized to either 8 wk of daily DGB (n = 12) or 8 wk of sham device (Sham; n = 13). BP, heart rate (HR), and MSNA were measured at rest and during mental math. Arterial BRS was assessed using the modified Oxford technique. Resting MSNA, BP, and heart rate (HR) remained comparable before and after 8 wk in both groups (DGB and Sham). Likewise, the change in sympathetic and cardiovagal BRS was not different between the groups. Interestingly, DGB significantly decreased MSNA reactivity to mental math when expressed as burst frequency (P = 0.012) or burst incidence (P = 0.008) compared with Sham, suggesting a sustained effect of DGB on sympathetic reactivity to stress in PTSD. Contrary to our hypothesis, long-term DGB did not lower systolic BP, diastolic BP, or HR responses to stress compared with Sham. Likewise, pulse pressure reactivity after 8 wk (P = 0.121) was also comparable. In summary, these data suggest that long-term use of DGB may lead to a sustained dampening of sympathetic reactivity to mental stress in PTSD.

The Impact of Exposure Therapy on Resting Heart Rate and Heart Rate Reactivity Among Active-Duty Soldiers With Posttraumatic Stress Disorder.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is linked to poor health, including cardiovascular disease. These effects may be a result of increased tonic cardiovascular function and cardiovascular reactivity. Despite PTSD's negative health burden, relatively little is known about whether frontline treatments for PTSD may alleviate cardiovascular risk. METHODS: The current study was a secondary analysis of a larger intervention study of active-duty soldiers with PTSD (n = 104; mean [SD] age = 30.6 [6.7] years; 6% women) randomized to an exposure therapy-either prolonged exposure (PE) or virtual reality exposure (VRE)-or a waitlist control condition. We examined change in participants' resting heart rate (HR) and HR reactivity from baseline (before randomization) to midtreatment and posttreatment using residualized change regression models. RESULTS: The results of the study demonstrated decreased resting HR (B = -5.06, p = .024) and HR reactivity (B = -2.46, p = .005) from baseline to posttreatment of PE and VRE relative to waitlist. Exploratory analyses found that changes in resting HR and HR reactivity were not significantly correlated with either self-reported or clinician-rated PTSD symptom change. CONCLUSIONS: These results suggest that PE and VRE for PTSD may alleviate some cardiovascular health risk associated with PTSD, improving cardiovascular functioning.RCT Registration: ClinicalTrials.gov (identifier: NCT01193725).

Symptom severity impacts sympathetic dysregulation and inflammation in post-traumatic stress disorder (PTSD).

Post-traumatic stress disorder (PTSD) is associated with a greater risk of incident hypertension and cardiovascular disease. Inflammation, impaired baroreflex sensitivity (BRS) decreased parasympathetic nervous system (PNS) and overactive sympathetic nervous system (SNS) activity are suggested as contributing mechanisms. Increasing severity of PTSD symptoms has been linked to greater cardiovascular risk; however, the impact of PTSD symptom severity on inflammation and autonomic control of blood pressure has not yet been explored. We hypothesized that increasing PTSD symptom severity is linked to higher inflammation, greater SNS activity, lower PNS reactivity and impaired BRS. Seventy Veterans participated in this study: 28 with severe PTSD ((Clinical Administered PTSD Scale (CAPS) > 60; S-PTSD), 16 with moderate PTSD (CAPS ≥ 45 ≤ 60; M-PTSD) and 26 Controls (CAPS < 45; NO-PTSD). We recorded continuous blood pressure (BP), heart rate (HR) via EKG, heart rate variability (HRV) markers reflecting PNS and muscle sympathetic nerve activity (MSNA) at rest, during arterial baroreflex sensitivity (BRS) testing via the modified Oxford technique, and during 3 min of mental stress via mental arithmetic. Blood samples were analyzed for 12 biomarkers of systemic and vascular inflammation. While BP was comparable between severity groups, HR tended to be higher (p = 0.055) in S-PTSD (76 ±â€¯2 beats/min) than in Controls (67 ±â€¯2 beats/min) but comparable to M-PTSD (70 ±â€¯3 beats/min). There were no differences in resting HRV and MSNA between groups; however, cardiovagal BRS was blunted (p = 0.021) in S-PTSD (10 ±â€¯1 ms/mmHg) compared to controls (16 ±â€¯3 ms/mmHg) but comparable to M-PTSD (12 ±â€¯2 ms/mmHg). Veterans in the S-PTSD group had a higher (p < 0.001) combined inflammatory score compared to both M-PTSD and NO-PTSD. Likewise, while mental stress induced similar SNS and cardiovascular responses between the groups, there was a greater reduction in HRV in S-PTSD compared to both M-PTSD and NO-PTSD. In summary, individuals with severe PTSD symptoms have higher inflammation, greater impairment of BRS, a trend towards higher resting HR and exaggerated PNS withdrawal at the onset of mental stress that may contribute to cardiovascular risk in severe PTSD.

A Review of PTSD Augmentation Strategies for Older Adults and Case of rTMS-Augmented Prolonged Exposure.

Evidence-based psychotherapies such as prolonged exposure therapy (PE) are recommended by clinical practice guidelines as first-line treatments for post-traumatic stress disorder (PTSD) and are safe and acceptable for use with older adults. One third to one half of all patients do not achieve a clinically meaningful response to standard outpatient PE and recent research suggests that older adults in particular may experience barriers to full engagement and response. Standard treatment may be challenging in older adults due to cognitive, medical, and psychosocial barriers. This article reviews the current state of the evidence on adjunctive and second-tier interventions that show promise for increasing response and/or engagement in evidence-based psychotherapy for PTSD, including medications such as d-cycloserine and 3,4-methylenedioxy-methamphetamine, neuromodulation techniques such as repetitive transcranial magnetic stimulation, and augmentations to the structure and content of psychotherapy, such as intensive outpatient formats. A case illustration of successful application of multiple augmentations to PE with an initially nonresponsive older adult patient is presented. A creative interdisciplinary approach based in available research may be beneficial for older adults who do not respond to first-line treatments.

Investigation of optimal dose of early intervention to prevent posttraumatic stress disorder: A multiarm randomized trial of one and three sessions of modified prolonged exposure.

BACKGROUND: Posttraumatic stress disorder (PTSD) is linked to a specific event, providing the opportunity to intervene in the immediate aftermath of trauma to prevent the development of this disorder. A previous trial demonstrated that trauma survivors who received three sessions of modified prolonged exposure therapy demonstrated decreased PTSD and depression prospectively compared to assessment only. The present study investigated the optimal dosing of this early intervention to test one versus three sessions of exposure therapy in the immediate aftermath of trauma. METHODS: Participants (n = 95) recruited from a Level 1 Trauma Center were randomly assigned in a 1.5:1.5:1 ratio in a parallel-group design to the three conditions: one-session exposure therapy, three-session exposure therapy, and assessment only. Follow-up assessments were conducted by study assessors blind to study condition. RESULTS: Mixed-effects model results found no significant differences in PTSD or depression symptoms between the control condition and those who received one or three exposure therapy sessions across 1-12-month follow-up assessment. Results indicate that the intervention did not interfere with natural recovery. Receiver operating characteristic curve analyses on the screening measure used for study inclusion (Predicting PTSD Questionnaire; PPQ) in the larger sample from which the treatment sample was drawn (n = 481) found that the PPQ was a poor predictor of likely PTSD at all follow-up time points (Area under the curve's = 0.55-0.62). CONCLUSIONS: This likely impacted study results as many participants demonstrated natural recovery. Recommendations for future early intervention research are reviewed, including strategies to identify more accurately those at risk for PTSD and oversampling more severe trauma types.

Acute effects of device-guided slow breathing on sympathetic nerve activity and baroreflex sensitivity in posttraumatic stress disorder.

Patients with posttraumatic stress disorder (PTSD) have elevated sympathetic nervous system reactivity and impaired sympathetic and cardiovagal baroreflex sensitivity (BRS). Device-guided slow breathing (DGB) has been shown to lower blood pressure (BP) and sympathetic activity in other patient populations. We hypothesized that DGB acutely lowers BP, heart rate (HR), and improves BRS in PTSD. In 23 prehypertensive veterans with PTSD, we measured continuous BP, ECG, and muscle sympathetic nerve activity (MSNA) at rest and during 15 min of DGB at 5 breaths/min ( n = 13) or identical sham device breathing at normal rates of 14 breaths/min (sham; n = 10). Sympathetic and cardiovagal BRS was quantified using pharmacological manipulation of BP via the modified Oxford technique at baseline and during the last 5 min of DGB or sham. There was a significant reduction in systolic BP (by -9 ± 2 mmHg, P < 0.001), diastolic BP (by -3 ± 1 mmHg, P = 0.019), mean arterial pressure (by -4 ± 1 mmHg, P = 0.002), and MSNA burst frequency (by -7.8 ± 2.1 bursts/min, P = 0.004) with DGB but no significant change in HR ( P > 0.05). Within the sham group, there was no significant change in diastolic BP, mean arterial pressure, HR, or MSNA burst frequency, but there was a small but significant decrease in systolic BP ( P = 0.034) and MSNA burst incidence ( P = 0.033). Sympathetic BRS increased significantly in the DGB group (-1.08 ± 0.25 to -2.29 ± 0.24 bursts·100 heart beats-1·mmHg-1, P = 0.014) but decreased in the sham group (-1.58 ± 0.34 to -0.82 ± 0.28 bursts·100 heart beats-1·mmHg-1, P = 0.025) (time × device, P = 0.001). There was no significant difference in the change in cardiovagal BRS between the groups (time × device, P = 0.496). DGB acutely lowers BP and MSNA and improves sympathetic but not cardiovagal BRS in prehypertensive veterans with PTSD. NEW & NOTEWORTHY Posttraumatic stress disorder is characterized by augmented sympathetic reactivity, impaired baroreflex sensitivity, and an increased risk for developing hypertension and cardiovascular disease. This is the first study to examine the potential beneficial effects of device-guided slow breathing on hemodynamics, sympathetic activity, and arterial baroreflex sensitivity in prehypertensive veterans with posttraumatic stress disorder.

Elevated resting blood pressure augments autonomic imbalance in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is characterized by increased sympathetic nervous system (SNS) activity, blunted parasympathetic nervous system (PNS) activity, and impaired baroreflex sensitivity (BRS), which contribute to accelerated cardiovascular disease. Patients with PTSD also have chronic stress-related elevations in resting blood pressure (BP), often in the prehypertensive range; yet, it is unclear if elevated resting blood pressure (ERBP) augments these autonomic derangements in PTSD. We hypothesized that compared with normotensive PTSD (N-PTSD), those with ERBP (E-PTSD) have further increased SNS, decreased PNS activity, and impaired BRS at rest and exaggerated SNS reactivity, PNS withdrawal, and pressor responses during stress. In 16 E-PTSD and 17 matched N-PTSD, we measured continuous BP, ECG, muscle sympathetic nerve activity (MSNA), and heart rate variability (HRV) markers reflecting cardiac PNS activity [standard deviation of R-R intervals (SDNN), root mean square of differences in successive R-R intervals (RMSSD), and high frequency power (HF)] during 5 min of rest and 3 min of mental arithmetic. Resting MSNA ( P = 0.943), sympathetic BRS ( P = 0.189), and cardiovagal BRS ( P = 0.332) were similar between groups. However, baseline SDNN (56 ± 6 vs. 78 ± 8 ms, P = 0.019), RMSSD (39 ± 6 vs. 63 ± 9 ms, P = 0.018), and HF (378 ± 103 vs. 693 ± 92 ms2, P = 0.015) were lower in E-PTSD versus N-PTSD. During mental stress, the systolic blood pressure response ( P = 0.011) was augmented in E-PTSD. Although MSNA reactivity was not different ( P > 0.05), the E-PTSD group had an exaggerated reduction in HRV during mental stress ( P < 0.05). PTSD with ERBP have attenuated resting cardiac PNS activity, coupled with exaggerated BP reactivity and PNS withdrawal during stress.

Virtual reality exposure versus prolonged exposure for PTSD: Which treatment for whom?

BACKGROUND: The majority of studies comparing active psychological treatments for posttraumatic stress disorder (PTSD) do not find significant differences at posttreatment. This was the case in a recent trial examining prolonged exposure (PE) and virtual reality exposure (VRE) among active-duty soldiers with combat-related PTSD. Matching individual patients to specific treatments provides a potential avenue to improve significantly the public health impact of effective treatments for PTSD. A composite moderator approach was used to identify profiles of patients who would see superior PTSD symptom reduction in VRE or PE to inform future treatment matching. METHODS: Active duty U.S. army soldiers (N = 108) were enrolled in a randomized clinical trial comparing VRE and PE in the treatment of PTSD stemming from deployments to Iraq or Afghanistan. Eighteen baseline variables were examined to identify treatment response heterogeneity in two patient groups: those with a superior response to PE and those with a superior response to VRE. The final composite moderator comprised four of 18 baseline variables. RESULTS: Results revealed that patients who were predicted to see greater PTSD symptom reduction in VRE were likely to be younger, not taking antidepressant medication, had greater PTSD hyperarousal symptoms, and were more likely to have greater than minimal suicide risk. CONCLUSIONS: Results suggest that treatment matching based on patient profiles could meaningfully improve treatment efficacy for combat-related PTSD. Future research can build on these results to improve our understanding of how to improve treatment matching for PTSD.

Narratives in the Immediate Aftermath of Traumatic Injury: Markers of Ongoing Depressive and Posttraumatic Stress Disorder Symptoms.

In this study, we considered connections between the content of immediate trauma narratives and longitudinal trajectories of negative symptoms to address questions about the timing and predictive value of collected trauma narratives. Participants (N = 68) were individuals who were admitted to the emergency department of a metropolitan hospital and provided narrative recollections of the traumatic event that brought them into the hospital that day. They were then assessed at intervals over the next 12 months for depressive and posttraumatic symptom severity. Linguistic analysis identified words involving affect (positive and negative emotions), sensory input (sight, sound, taste, touch, and smell), cognitive processing (thoughts, insights, and reasons), and temporal focus (past, present, and future) within the narrative content. In participants' same-day narratives of the trauma, past-focused utterances predicted greater decreases in depressive symptom severity over the next year, d = -0.13, whereas cognitive process utterances predicted more severe posttraumatic symptom severity across time points, d = 0.32. Interaction analyses suggested that individuals who used fewer past-focused and more cognitive process utterances within their narratives tended to report more severe depressive and posttraumatic symptom severity across time, ds = 0.31 to 0.34. Overall, these findings suggest that, in addition to other demographics and baseline symptom severity, early narrative content can serve as an informative marker for longitudinal psychological symptoms, even before extensive narrative processing and phenomenological meaning-making have occurred.

Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post-traumatic stress disorder.

KEY POINTS: Patients with post-traumatic stress disorder (PTSD) are at a significantly higher risk of developing hypertension and cardiovascular disease. The mechanisms underlying this increased risk are not known. Studies have suggested that PTSD patients have an overactive sympathetic nervous system (SNS) that could contribute to cardiovascular risk; however, sympathetic function has not previously been rigorously evaluated in PTSD patients. Using direct measurements of sympathetic nerve activity and pharmacological manipulation of blood pressure, we show that veterans with PTSD have augmented SNS and haemodynamic reactivity during both combat-related and non-combat related mental stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and increased inflammation. Identifying the mechanisms contributing to increased cardiovascular (CV) risk in PTSD will pave the way for developing interventions to improve sympathetic function and reduce CV risk in these patients. ABSTRACT: Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic nervous system (SNS) and haemodynamic reactivity during mental stress, as well as impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy Veterans with combat-related PTSD were compared with 14 matched Controls without PTSD.  Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP) and electrocardiography were measured at baseline, as well as during two types of mental stress:  combat-related mental stress using virtual reality combat exposure (VRCE) and non-combat related stress using mental arithmetic (MA). A cold pressor test (CPT) was administered for comparison. BRS was tested using pharmacological manipulation of BP via the Modified Oxford technique at rest and during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline characteristics, MSNA and haemodynamics were similar between the groups. In PTSD vs. Controls, MSNA (+8.2 ± 1.0 vs. +1.2 ± 1.3 bursts min-1 , P < 0.001) and heart rate responses (+3.2 ± 1.1 vs. -2.3 ± 1.0 beats min-1 , P = 0.003) were significantly augmented during VRCE.  Similarly, in PTSD vs. Controls, MSNA (+21.0 ± 2.6 vs. +6.7 ± 1.5 bursts min-1 , P < 0.001) and diastolic BP responses (+6.3 ± 1.0 vs. +3.5 ± 1.0 mmHg, P = 0.011) were significantly augmented during MA but not during CPT (P = not significant). In the PTSD group, sympathetic BRS (-1.2 ± 0.2 vs. -2.0 ± 0.3 burst incidence mmHg-1 , P = 0.026) and cardiovagal BRS (9.5 ± 1.4 vs. 23.6 ± 4.3 ms mmHg-1 , P = 0.008) were significantly blunted at rest. PTSD patients had significantly higher highly sensitive-C-reactive protein levels compared to Controls (2.1 ± 0.4 vs. 1.0 ± 0.3 mg L-1 , P = 0.047). Augmented SNS and haemodynamic responses to mental stress, blunted BRS and inflammation may contribute to an increased CV risk in PTSD.

Mobile assessment of heightened skin conductance in posttraumatic stress disorder.

BACKGROUND: Increased psychophysiological reactivity is a hallmark intermediate phenotype of posttraumatic stress disorder (PTSD). Individuals with PTSD exhibit greater skin conductance (SC) responses to trauma scripts than trauma survivors without PTSD. However, trauma scripts require time for development and cannot be easily used in a single visit. Thus, there is a need for a low-cost, easy-to-use, SC recording protocol for PTSD assessment. METHODS: Using a mobile device (eSense) connected to a portable tablet computer, we assessed SC reactivity to a standard trauma interview (STI) in 63 participants recruited from Grady Memorial Hospital in Atlanta, GA, approximately 1 year after trauma exposure. SC response (SCR) was calculated by subtracting the SC level (SCL) at the end of the baseline recording from the maximum SCL during the STI. RESULTS: SCL was significantly higher during the STI compared to baseline (P < .001), and individuals with PTSD showed significantly greater SCR than individuals without PTSD (P = .006). Logistic regression using SCR with PTSD diagnosis as the outcome showed an odds ratio of 1.76 (95% CI: 1.11-2.78). Lastly, higher SCR during the STI was also significantly associated with PTSD symptom total score controlling for demographics and trauma severity (b = 0.42, P = .001). CONCLUSIONS: The current study demonstrated feasibility of the use of a mobile device for assessing psychophysiological reactivity in those with PTSD. The use of this low-cost, easy-to-use mobile device to collect objective physiological data in concert with a STI can be easily disseminated in clinical and research settings.