Testing the role of aerobic exercise in the treatment of posttraumatic stress disorder (PTSD) symptoms in U.S. active duty military personnel: a pilot study.

The purpose of this pilot study was to determine if the efficacy of imaginal exposure for symptoms of posttraumatic stress disorder (PTSD) could be improved by adding aerobic exercise. We hypothesized that aerobic exercise would enhance the efficacy of exposure therapy. Active duty service members with clinically significant symptoms of posttraumatic stress (PTSD Checklist-Stressor-Specific Version, [PCL-S], ≥25) were randomized into one of four conditions: exercise only; imaginal exposure only; imaginal exposure plus exercise; no exercise/no exposure therapy (control). Participants (N = 72) were primarily male, Army, noncommissioned officers ranging in age from 22 to 52. PTSD symptom severity decreased over time (p < .0001); however, there were no significant differences between the experimental conditions. The prediction that imaginal exposure augmented with aerobic exercise would be superior to either imaginal exposure alone or aerobic exercise alone was not supported, suggesting that engaging in exercise and imaginal exposure simultaneously may not be any better than engaging in either activity alone. A better understanding of individually administered and combined exercise and exposure therapy interventions for PTSD is warranted.

5-HT2A receptors in the orbitofrontal cortex facilitate reversal learning and contribute to the beneficial cognitive effects of chronic citalopram treatment in rats.

Chronic stress is a risk factor for depression, and chronic stress can induce cognitive impairments associated with prefrontal cortical dysfunction, which are also major components of depression. We have previously shown that 5 wk chronic intermittent cold (CIC) stress induced a reversal-learning deficit in rats, associated with reduced serotonergic transmission in the orbitofrontal cortex (OFC) that was restored by chronic treatment with a selective serotonin reuptake inhibitor (SSRI). However, the mechanisms underlying the beneficial cognitive effects of chronic SSRI treatment are currently unknown. Thus, the purpose of this study was to investigate the potential modulatory influence specifically of 5-HT2A receptors (5-HT2ARs) in the OFC on reversal learning, and their potential contribution to the beneficial cognitive effects of chronic SSRI treatment. Bilateral microinjections of the selective 5-HT2AR antagonist, MDL 100,907 into OFC (0.02-2.0 nmol) had a dose-dependent detrimental effect on a reversal-learning task, suggesting a facilitatory influence of 5-HT2ARs in the OFC. In the next experiment, rats were exposed to 5 wk CIC stress, which compromised reversal learning, and treated chronically with the SSRI, citalopram (20 mg/kg.d) during the final 3 wk of chronic stress. Chronic citalopram treatment improved reversal learning in the CIC-stressed rats, and bilateral microinjection of MDL 100,907 (0.20 nmol, the optimal dose from the preceding experiment) into OFC once again had a detrimental effect on reversal learning, opposing the beneficial effect of citalopram. We conclude that 5-HT2ARs in the OFC facilitate reversal learning, and potentially contribute to the beneficial cognitive effects of chronic SSRI treatment.

STRONG STAR and the Consortium to Alleviate PTSD: Shaping the future of combat PTSD and related conditions in military and veteran populations.

The STRONG STAR Consortium (South Texas Research Organizational Network Guiding Studies on Trauma and Resilience) and the Consortium to Alleviate PTSD are interdisciplinary and multi-institutional research consortia focused on the detection, diagnosis, prevention, and treatment of combat-related posttraumatic stress disorder (PTSD) and comorbid conditions in military personnel and veterans. This manuscript outlines the consortia's state-of-the-science collaborative research model and how this can be used as a roadmap for future trauma-related research. STRONG STAR was initially funded for 5 years in 2008 by the U.S. Department of Defense's (DoD) Psychological Health and Traumatic Brain Injury Research Program. Since the initial funding of STRONG STAR, almost 50 additional peer-reviewed STRONG STAR-affiliated projects have been funded through the DoD, the U.S. Department of Veterans Affairs (VA), the National Institutes of Health, and private organizations. In 2013, STRONG STAR investigators partnered with the VA's National Center for PTSD and were selected for joint DoD/VA funding to establish the Consortium to Alleviate PTSD. STRONG STAR and the Consortium to Alleviate PTSD have assembled a critical mass of investigators and institutions with the synergy required to make major scientific and public health advances in the prevention and treatment of combat PTSD and related conditions. This manuscript provides an overview of the establishment of these two research consortia, including their history, vision, mission, goals, and accomplishments. Comprehensive tables provide descriptions of over 70 projects supported by the consortia. Examples are provided of collaborations among over 50 worldwide academic research institutions and over 150 investigators.

Veterans Team Recovery Integrative Immersion Process (Vet TRIIP): A Qualitative Evaluation of Participation and Impact.

INTRODUCTION: The Veterans Team Recovery Integrative Immersion Process (Vet TRIIP) is a short-term multi-modality complementary, integrative immersion program for veterans with chronic pain, post-traumatic stress, and related symptoms. Geared toward Veterans, active duty servicemembers, family members, and caregivers, Vet TRIIP aims to honor and empower them to create healthy, happy, and productive civilian lives. This study evaluates the program to determine its impact on the quality of life and ways to improve and develop Vet TRIIP. MATERIALS AND METHODS: In total, 14 clients participated in the qualitative review of the Vet TRIIP program in San Antonio. The participants were interviewed related to their reason for participating, their most bothersome symptoms and the effects of Vet TRIIP on those symptoms, service provided that is most and least appreciated, suggestions for improvement, and things learned from Vet TRIIP that helped them daily. Responses were analyzed for emerging themes. RESULTS: The main reasons for participating were physiological and psychological needs, social support, and curiosity to address their reported symptoms such as pain, stress/anxiety, and depression. Vet TRIIP reportedly improved their quality of life and decreased stress. The participants liked most the support of the Vet TRIIP staff and the interventions such as reiki and massage. Other participants did not like acupuncture. Participants suggested the addition of professional psychological services could be helpful. They reported that emotional freedom technique (EFT/tapping) and guided breathing were most useful in their daily lives. Each participant reported that Vet TRIIP was a positive experience that helped with their pain, anxiety, and stress management, providing an improvement in their quality of life. It also imparted an eye-opening experience to nontraditional non-pharmacological interventions for pain, anxiety, and stress. CONCLUSIONS: Evaluative studies on organizations that support Veterans are useful to gauge the effectiveness and impact. Through this study, Veterans expressed perceived strengths and weaknesses of the program so further development and appropriate services will be provided. Similar studies on the impact of non-profit organizations are encouraged. Vet TRIIP significantly impacts the lives of many through stress and pain reduction, potentially preventing suicide.

Testing a variable-length Cognitive Processing Therapy intervention for posttraumatic stress disorder in active duty military: Design and methodology of a clinical trial.

Combat-related trauma exposures have been associated with increased risk for posttraumatic stress disorder (PTSD) and comorbid mental health conditions. Cognitive Processing Therapy (CPT) is a 12-session manualized cognitive-behavioral therapy that has emerged as one of the leading evidence-based treatments for combat-related PTSD among military personnel and veterans. However, rates of remission have been less in both veterans and active duty military personnel compared to civilians, suggesting that studies are needed to identify strategies to improve upon outcomes in veterans of military combat. There is existing evidence that varying the number of sessions in the CPT protocol based on patient response to treatment improves outcomes in civilians. This paper describes the rationale, design, and methodology of a clinical trial examining a variable-length CPT intervention in a treatment-seeking active duty sample with PTSD to determine if some service members would benefit from a longer or shorter dose of treatment, and to identify predictors of length of treatment response to reach good end-state functioning. In addition to individual demographic and trauma-related variables, the trial is designed to evaluate factors related to internalizing/externalizing personality traits, neuropsychological measures of cognitive functioning, and biological markers as predictors of treatment response. This study attempts to develop a personalized approach to achieving positive treatment outcomes for service members suffering from PTSD. Determining predictors of treatment response can help to develop an adaptable treatment regimen that returns the greatest number of service members to full functioning in the shortest amount of time.

Diabetes Changes Symptoms Cluster Patterns in Persons Living With HIV.

Approximately 10-15% of persons living with HIV (PLWH) have a comorbid diagnosis of diabetes mellitus (DM). Both of these long-term chronic conditions are associated with high rates of symptom burden. The purpose of our study was to describe symptom patterns for PLWH with DM (PLWH+DM) using a large secondary dataset. The prevalence, burden, and bothersomeness of symptoms reported by patients in routine clinic visits during 2015 were assessed using the 20-item HIV Symptom Index. Principal component analysis was used to identify symptom clusters. Three main clusters were identified: (a) neurological/psychological, (b) gastrointestinal/flu-like, and (c) physical changes. The most prevalent symptoms were fatigue, poor sleep, aches, neuropathy, and sadness. When compared to a previous symptom study with PLWH, symptoms clustered differently in our sample of patients with dual diagnoses of HIV and diabetes. Clinicians should appropriately assess symptoms for their patients' comorbid conditions.

Impact of stress on prefrontal glutamatergic, monoaminergic and cannabinoid systems.

Stress has been shown to have marked and divergent effects on learning and memory which involves specific brain regions, such as spatial and declarative memory involving the hippocampus, memory of emotional arousing experiences and fear involving the amygdala, and executive functions and fear extinction involving the prefrontal cortex or the PFC. Response to stress involves a coordinated activation of a constellation of physiological systems including the activation of the hypothalamic-pituitary-adrenal (HPA) axis and other modulatory neurotransmitters and signaling systems. This paper presents a concise review of the effects of stress and glucocorticoids on the glutamatergic and monoaminergic (including noradrenergic, dopaminergic, and serotonergic systems) neurotransmitter systems as well as endocannabinoid signaling. Because of the breadth of the scope of this topic, the review is limited to the effects of stress on these brain systems on the prefrontal cortex, and where relevant, the hippocampus and the amygdala.

Neurobehavioral Mechanisms of Traumatic Stress in Post-traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder that develops following trauma exposure. It is characterized by four symptom clusters: intrusion, avoidance, negative alteration in cognitions and mood, and alterations in arousal and reactivity. Several risk factors have been associated with PTSD, including trauma type and severity, gender and sexual orientation, race and ethnicity, cognitive reserve, pretrauma psychopathology, familial psychiatric history, and genetics. Great strides have been made in understanding the neurobiology of PTSD through animal models and human imaging studies. Most of the animal models have face validity, but they have limitations in the generalization to the human model of PTSD. Newer animal models, such as the "CBC" model, have better validity for PTSD, which takes into account the different components of its diagnostic criteria. To date, fear conditioning and fear extinction animal models have provided support for the hypothesis that PTSD is a dysregulation of the processes related to fear regulation and, especially, fear extinction. More research is needed to further understand these processes as they relate not only to PTSD but also to resilience. Further, this research could be instrumental in the development of novel effective treatments for PTSD.

Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats.

RATIONALE: Chronic stress perturbs modulatory brain neurotransmitter systems, including serotonin (5-HT), and is a risk factor for psychiatric disorders such as depression. Deficits in cognitive flexibility, reflecting prefrontal cortical dysfunction, are prominent in such disorders. Orbitofrontal cortex (OFC) has been implicated specifically in reversal learning, a form of cognitive flexibility modulated by 5-HT. OBJECTIVES: The objectives of the study were (1) to assess the effects of chronic intermittent cold (CIC) stress, a potent metabolic stressor, on performance of rats in an attentional set-shifting test (AST), and (2) to assess a possible role for serotonin in CIC-induced deficits and test the effects of acute serotonin reuptake blockade. MATERIALS AND METHODS: Male Sprague-Dawley rats were exposed to CIC stress (14 days x 6 h/day at 4 degrees C) before testing on the AST. In subsequent experiments, brain 5-HT was depleted in naïve rats with para-chlorophenylalanine or 5-HT release was increased acutely in CIC-stressed rats with citalopram (5 mg/kg, s.c.) given 30 min prior to the first reversal task. Microdialysis was used to assess CIC-induced changes in 5-HT release in OFC during testing. RESULTS: CIC-stressed rats exhibited a selective impairment on the first reversal task in the AST. 5-HT depletion induced a similarly selective deficit in reversal learning. The CIC-induced impairment in reversal learning was attenuated by acute 5-HT reuptake blockade. 5-HT release was reduced in OFC of CIC-stressed rats during behavioral testing. CONCLUSIONS: The CIC stress-induced impairment of cognitive flexibility may involve dysregulation of 5-HT modulatory function in OFC. Such deficits may thus model relevant symptoms of neuropsychiatric disorders that respond positively to SSRI treatment.