Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a chronic disorder that develops following exposure to trauma, and is characterized by intrusive experiences, avoidance, cognitive-emotional changes, and hyperarousal. It is based on a complex noradrenergic dysregulation. The amygdala activates the hypothalamus to release excessive corticotropin releasing factor (CRF), which activates the hypothalamic-pituitary-adrenal (HPA) axis and leads to high nocturnal cortisol levels with EEG changes and increased arousals. At the same time, the Locus Coeruleus (LC) releases excess norepinephrine (NE), which interferes with the transition to Non-REM sleep and suppresses the stability of REM sleep, a stage essential for emotional processing and the extinction of conditioned fear. Sleep disturbances occur in 70-90% of PTSD patients, leading to fragmented sleep that impairs conditioned fear extinction, reinforces hyperarousal, and perpetuates the disorder as a protective-morbidity mechanism \[1,2\]. Beyond the clinical implications, sleep disturbances mediate the relationship between PTSD and functional disability and occupational disability, with 74% of the economic burden of PTSD in Israel attributed to loss of employment and productivity (3,4). The Stellate Ganglion (SG), located between the C6-C7 vertebrae, is a central sympathetic junction between the central nervous system and the periphery. This connection is expressed in descending pathways from the amygdala and prefrontal cortex (PFC) and ascending pathways from the periphery through the SG that feed the LC, which in turn secretes NE to the amygdala and other limbic areas and affects fear and memory processing. Subganglionic ganglion block (SGB) using local anesthetic injection reduces sympathetic tone, reduces Nerve Growth Factor (NGF) and NE levels, and "breaks" the pathological feedback loop. This effect was found to reduce conditioned fear memory and was accompanied by a significant decrease in NE concentration in the amygdala (5,6). A multicenter RCT showed that SGB led to an improvement in PTSD symptoms, with sleep disturbances and hyperarousal being the most responsive symptoms \[7\]. This finding was supported by a recent meta-analysis that confirmed a significant improvement in key sleep measures, including total sleep time and overall sleep quality (8). A RCT that included a sleep laboratory and neurotransmitter measurements in anxiety patients with sleep disorders found that SGB led to a decrease in NE and an increase in Serotonin- and NPY-, along with an objective improvement in quality and time of wakefulness \[9\]. Initial findings in primary insomnia patients without PTSD also showed significant improvement, and combining SGB with CBT-I (cognitive-behavioral therapy) yielded stable results over time \[10\]. These findings strengthen the rationale for using SGB as a treatment for disorders resulting from sympathetic overactivity and HPA axis dysregulation. Despite this promising evidence, there is a knowledge gap: the effect of SGB on objective and continuous sleep measures in a natural setting has not yet been examined, and cortisol levels have not been measured concurrently with changes in sleep. Polysomnography (PSG)-the standard test for diagnosing sleep disorders-is not suitable for continuous monitoring due to discomfort. Wearable devices, in particular the Oura Ring Gen3, have been shown to be a valid alternative to PSG for sleep monitoring in a natural setting. The ring, which demonstrated the highest PSG compliance among consumer monitoring devices, combines accelerometry and photoplethysmography (PPG) to continuously measure WASO (Wake After Sleep Onset), Sleep efficiency (SE), Heart rate variability (HRV), sleep stages, and nocturnal heart rate (11,12). The proposed study aims to bridge this gap, to monitor for the first time objective physiological sleep measures and cortisol levels over time in PTSD patients after SGB. In addition to its contribution to understanding the mechanism of action of SGB, this study will isolate the physiological measures associated with clinical improvement and may serve as a gateway for further research and treatments in the field and for therapeutic success in PTSD and autonomic dysregulation.

The goal of this clinical trial is to evaluate the safety and effectiveness of the gammaCore non-invasive vagus nerve stimulation (nVNS) device as an additional treatment for symptoms of post-traumatic stress disorder (PTSD) in adults. The vagus nerve connects the brain with many organs and systems in the body and plays a role in regulating stress and emotional responses. The gammaCore device is a handheld, rechargeable medical device that delivers gentle electrical stimulation to the vagus nerve through the skin on the side of the neck. By stimulating this nerve, the device may help reduce PTSD symptoms. gammaCore is cleared by the U.S. Food and Drug Administration (FDA) for the treatment and prevention of migraine and cluster headache. It has not yet been approved for the treatment of PTSD. This study is being conducted to better understand whether this type of stimulation may help improve PTSD symptoms and to evaluate its safety when used for this purpose. The main questions this study aims to answer are: * Is non-invasive vagus nerve stimulation safe for people with PTSD when used regularly at home? * Does treatment with the gammaCore device improve PTSD symptom severity over time? In this study, approximately 40 adults with PTSD will participate in an open-label pilot study. Participants will first complete a 4-week baseline period in which their PTSD symptoms are monitored. This allows researchers to understand each participant's symptoms before starting the intervention. Participants will then begin a 12-week treatment period using the gammaCore device at home. During this time, participants will apply the device to the side of the neck for short stimulation sessions each day as instructed by the study team. Participants will attend six study visits, some conducted remotely and some in person. These visits include screening, training on how to use the device, and follow-up assessments. During the study, participants will complete questionnaires and clinician-administered assessments that measure PTSD symptoms and quality of life. Researchers will also monitor participants for any side effects or medical problems related to the device. By collecting information on symptoms, safety, and device use, this study will help researchers understand whether non-invasive vagus nerve stimulation could become a useful treatment option for people living with PTSD.

The proposed study will test whether a working memory training (WMT) program improves fear extinction learning and its underlying neural circuitry in Veterans with posttraumatic stress disorder (PTSD). WMT is designed to improves the ability to maintain task-relevant information in mind. The project will further validate the relationship between working memory and fear extinction using novel computational and multivariate analyses that link to specific PTSD symptoms. If WMT can enhance fear extinction learning, then WMT may be a powerful adjunctive treatment that can enhance exposure therapy outcomes or be leveraged as a stand-alone treatment. This project supports the Department of Veteran Affairs mission of developing viable targets of treatment for Veterans with PTSD.

The goal of this study is to test whether anesthesia-induced experiences can help alleviate symptoms of PTSD in an (1) open-label trial (Phase I) and (2) single-center double-blind, randomized, active-comparator (dose-controlled) participant-and assessor-blinded Phase 2 clinical trial (Phase II) in a non-surgical setting. Participants will undergo EEG-guided propofol anesthesia during which they will be either (1) receiving a sedation protocol associated with dream experiences upon emergence (Dream Condition), and/or (2) a sedation protocol associated with non-dream experiences (Non-Dream Condition). The investigators will then investigate whether the Dream Condition is associated with a larger reduction in PTSD symptoms than the Non-Dream Condition.

Populations facing health disparities include groups with significantly higher rates of posttraumatic stress disorder than the general population who frequently experience lived experience stress, which may complicate posttraumatic stress disorder symptom presentations. However, there are currently no posttraumatic stress disorder treatments designed to meet the unique needs of these individuals. The proposed study will pilot an adaptation of Cognitive Processing Therapy (a gold-standard treatment for posttraumatic stress disorder) that has been modified to incorporate the impact of lived experience stress as an additional treatment target. This project has the potential to advance our understanding of how to enhance Cognitive Processing Therapy in order to optimize posttraumatic stress disorder treatment response and mitigate health disparities.

This is a single-center cross-sectional study conducted on a sample of former military personnel who had been diagnosed with PTSD. The main objective of this study is to test a mediation model positing that PTSD increases individuals' levels of anger through its detrimental effect on social cognitive abilities (Quantitative component). The secondary objectives focus on the impact of alcohol consumption and ACE on the three components (theory of mind, emotional decoding, empathy) of social cognition (qualitative component). A second secondary objective aims to explore the moral harms reported by former military personnel through a qualitative analysis of semi-structured interviews (qualitative component). Primary Objective (Quantitative Component): To examine the links between PTSD, anger, and social cognition among French veterans using mediation analyses. The aim is to test whether PTSD (independent variable) indirectly influences individuals' levels of anger (dependent variable) through its effect on social cognition (mediating variable). Secondary Objectives: * Quantitative component: to examine other factors associated with PTSD that may influence social cognitive abilities, such as alcohol consumption and experiences of childhood abuse (Abuse Childhood Experience-ACE); * Qualitative component: to explore the psychological trauma experienced by military personnel through a qualitative analysis of semi-structured interviews. Evaluation criteria: Main Components: Quantitative Component Self-report scales for PTSD, anger, and empathy, as well as two social cognition tasks: * PCL-5 - Posttraumatic Checklist-5 * STAXI-2 - Spielberger's State-Trait Anger Expression Inventory-2 * EQ - Empathy Quotient * MASC - Movie for the Assessment of Social Cognition * TREF - Facial Emotion Recognition Test Secondary: 1. Quantitative component Self-reported scales of alcohol use, childhood abuse experiences, and anxiety and depression: * AUDIT - Alcohol Use Disorders Identification Test * ACE-IQ - Adverse Childhood Experiences-International Questionnaire * HADS - Hospital Anxiety and Depression Scale 2. Qualitative component - Content of verbatim transcripts from semi-structured interviews

This study is evaluating the safety and efficacy of TSND-201 in adults with PTSD. Eligible participants will enter a 4-week Treatment Period where they will be randomized 1:1:1 to receive one of two doses of TSND-201 or placebo, once per week. Following the Treatment Period, participants will enter an 8-week Follow-up Period.

Many combat veterans (c-Vs), service members (SMs) and civilians with mild traumatic brain injury (mTBI, also termed concussion) suffer from persistent post-concussion symptoms (PPCS) that degrade physical and cognitive well-being and have been linked with early neurodegeneration. PPCS include somatosensory (e.g., headache, disturbed vision), vestibular (e.g., dizzy, clumsy), cognitive (e.g., executive function, memory) and affective symptoms (e.g., sleep disturbance, irritability, depression). A key pathological process that provokes and perpetuates PPCS is autonomic nervous system (ANS) dysfunction such as unremitting sympathetic nervous system activation that also exacerbates other pathology such as inflammation. ANS activity can be readily quantified by measuring heart rate variability (HRV), or the variation in heart rate over time, which serves as a valid index of both physiological and psychological health

The MIRROR study will compare the effectiveness of two interventions in improving emotion regulation and reducing PTSD symptoms in female Veterans with military sexual trauma (MST) and/or intimate partner violence (IPV) and co-occurring brain injury.

This study aims to evaluate the effects of integrating trauma-informed care (TIC) into the organizational structure of maternity services on women giving birth and healthcare professionals involved in perinatal care. The study will be conducted at Tarsus State Hospital and will implement a systematic, organization-wide TIC approach designed to improve the quality and psychological safety of maternity care. Trauma-informed care recognizes the potential impact of previous and birth-related trauma and seeks to prevent re-traumatization through respectful communication, emotional safety, informed consent, empowerment, collaborative decision-making, and support for women's autonomy and dignity. In maternity services, these principles may contribute to more positive childbirth experiences while also supporting healthcare professionals who may experience secondary traumatic stress through repeated exposure to traumatic events. The intervention will involve multiple groups within the hospital, including organizational leaders, healthcare professionals, and support personnel. Organizational leaders will receive training on institutional implementation of TIC and the development of sustainable organizational strategies. Healthcare professionals, including midwives, nurses, obstetricians, psychologists, psychiatrists, and social workers, will receive training on recognizing trauma, trauma-sensitive communication, and integrating TIC principles into routine maternity care. Support personnel will receive training focused on respectful communication and awareness of trauma-related sensitivities. Educational activities will include case discussions, group exercises, role-playing, and problem-solving sessions. The study will evaluate whether this organization-wide approach contributes to improved trauma-informed practices among healthcare professionals and more positive experiences among women receiving maternity care.

This study is evaluating the safety and efficacy of TSND-201 in adults with PTSD. Eligible participants will enter a 4-week Treatment Period where they will be randomized 1:1:1 to receive one of two doses of TSND-201 or placebo, once per week. Following the Treatment Period, participants will enter an 8-week Follow-up Period.

PTSD occurs in up to 17% of post-9/11 US Service Members and is associated with long-term functional impairment, family problems, unemployment, and suicidality. Trauma-focused therapies (TFTs), such as Prolonged Exposure (PE), result in significant relief for many. Yet, TFTs are not equally effective for everyone. An important minority (\~40%) will retain their PTSD diagnoses after treatment, and many discontinue treatment prematurely, especially post-9/11 Service Members. TFTs are also more effective in addressing symptoms than psychosocial functioning. More work is needed to improve the consistency and potency of TFTs. Partnering with significant others may provide a powerful method for helping individuals get more out of their PTSD treatment. Observational research shows that relationship factors can help patients initiate, stay in, and experience greater benefit from PTSD treatment. Veterans that were surveyed experienced greater treatment gains when they shared more about their treatment with loved ones and when loved ones accommodated less for PTSD symptoms. Despite the promise of partner-involved interventions, there is no couples approach to PTSD treatment that has demonstrated superior outcomes to individual-only treatment models (i.e., TFTs). To address this gap, the investigators have completed a series of partner-assisted PTSD treatment studies, leading up the current proposal (Partnered PE, PPE). The investigators found that treatment completion rates were better than routine clinical care, and the treatment led to large improvements in participants' functioning, PTSD symptoms, and romantic functioning. For this proposed study, the primary objective is to conduct a randomized controlled trial (Research Level 3; larger-scale clinical trial) to test the superiority of PPE to standard PE among post 9/11 Veterans. The investigator's primary hypothesis is that PPE will lead to greater improvements in psychosocial functioning than standard PE. Secondary and tertiary aims examine posttreatment clinical outcomes (PTSD, depression) and intimate partner outcomes (relationship functioning, distress, caregiver burden, and psychosocial functioning), as well as examine strategies for PPE implementation. In exploratory aims, the investigators will examine the stability of group differences, treatment completion rates, the role military sexual trauma history, and treatment mechanisms.

Investigators' overall objective is to compare methods of identifying individuals who may be experiencing challenges in Cognitive Processing Therapy (CPT) and compare methods of intervening to optimize treatment retention and outcomes. Investigators' specific aims are: 1. to determine whether the use of CPT skills versus collaboratively considering switching to Present Centered Therapy (PCT) is more effective in improving outcomes for individuals experiencing challenges with CPT. Outcomes include post-traumatic stress disorder (PTSD) severity \[primary\], depression, functioning, and treatment retention; 2. to compare two approaches to identifying individuals in CPT in need of additional support during treatment; 3. to study the barriers and facilitators of implementing these intervention strategies. Finally, exploratory aims will examine the stability of differences between treatment conditions, compare combinations of interventions tested, and examine moderators of intervention effects.

Efficacy of a Multi-level School Intervention for LGBTQ Youth

The overall objective of this study it to use Positron Emission Tomography (PET) brain imaging and a radiotracer that measures the epigenetic marker Histone Deacetylase 6 (HDAC6) to examine HDAC6 expression in people with Post-Traumatic Stress Disorder (PTSD), Alcohol Use Disorder (AUD), or concurrent PTSD and AUD with control groups. While there are a large number of studies conducted in preclinical stress and addiction models, these findings have not been translated to people living with these disorders. This study will examine relationships between HDAC6 and clinical variables of interest. Findings could direct treatment development.

The investigators want to test a treatment for posttraumatic stress disorder (PTSD) especially designed for military veterans and service members with mild or moderate traumatic brain injuries (TBI) and PTSD. The treatment will include individual psychotherapy sessions to manage PTSD.

The overall strategy is to recruit veterans with PTSD who report minimal current cannabis use but are interested in or considering therapeutic cannabis to manage mental health symptoms (anxiety, depression, PTSD and/or suicidality). The information gained from this study could lead to the development of new treatments for persons who suffer from post-traumatic stress disorder and maintain better mental health.

The purpose of this study is to examine the benefits of combining repetitive Transcranial Magnetic Stimulation (rTMS) coupled with Cognitive Processing Therapy (CPT) in treating combat-related Posttraumatic Stress Disorder (PTSD) symptoms. The study will also examine change in depression, psychosocial functioning, and neurophysiological (i.e., electroencephalography and magnetic resonance images) measures.

This study aims to evaluate the safety, feasibility, acceptability, and effectiveness of MDMA-assisted Cognitive-Behavioral Conjoint Therapy (CBCT) versus CBCT alone for the treatment of Post-Traumatic Stress Disorder (PTSD). PTSD is a debilitating condition that significantly impacts interpersonal relationships and the functioning of individuals and their loved ones. There is also a well-established reciprocal relationship between interpersonal relationships, PTSD, and recovery. CBCT is a manualized treatment for PTSD that simultaneously addresses PTSD symptoms and relationship satisfaction. It provides dyads with behavioral tools to navigate PTSD-related challenges, as well as the knowledge behind PTSD and how it impacts relationships. Previous research has demonstrated the efficacy of CBCT in improving PTSD symptoms, partner functioning, and relationship satisfaction in both distressed and non-distressed dyads. MDMA is a drug commonly used recreationally that has been increasingly studied because of its ability to reduce the impact of PTSD symptoms. The effects of MDMA are reduced fear, enhanced communication, trust and introspection, and increased empathy and compassion. The effects of MDMA create a state that enhances the positive effects of therapy by increasing the ability to tolerate negative emotions and allowing clients to stay engaged in therapy without being overwhelmed by the intense emotions surrounding the memories of traumatic events. It is believed that MDMA may help promote the effects of CBCT due to its ability to induce empathy and interpersonal openness. This randomized study is the second study designed to explore the efficacy of combining MDMA-assisted therapy with CBCT. This study will enroll 30 dyads, where one individual has symptoms of PTSD. Participants will undergo a 7-week psychotherapy course, in MDMA-assisted CBCT or CBCT alone. In the MDMA-assisted CBCT, participants will go through CBCT sessions, and two doses of MDMA will be used as an adjunct to psychotherapy. Participants assigned to the CBCT-only condition will go through CBCT sessions and will have the opportunity to crossover and receive the two MDMA sessions after follow-up. The primary goal of this research is to contribute to the literature on MDMA-assisted CBCT by investigating its feasibility, safety, acceptability, and effectiveness, and by comparing it to active PTSD treatments.

This randomized, double-blind, single-site phase II 2-arm study will investigate the safety and preliminary efficacy of MDMA-assisted therapy compared with low dose d-amphetamine-assisted therapy on the severity of PTSD symptoms in participants aged 18 years and older with PTSD of at least moderate severity.

This study is a randomized, controlled clinical trial to examine the therapeutic potential of cannabinoids for treating veterans with PTSD and suicidal ideation.

The goal of this clinical trial is to develop a new behavioral treatment for U.S. combat veterans with post-traumatic stress disorder (PTSD), very brief exposure to combat-related stimuli. The main questions it aims to answer are: 1. How does Very Brief Exposure (combat images and control everyday images) and Visible Exposure to combat stimuli affect brain activity and subjective fear ratings? 2. To what extent are participants aware of the stimuli presented and tolerating the exposures? All participants will view both very brief exposure and visible exposure to combat stimuli in the functional magnetic brain imaging (fMRI) scan. They will provide ratings of fear, awareness, and tolerability. Researchers will compare U.S. combat veterans with PTSD and healthy controls to confirm differences in brain region activation and ratings.

This study is designed to better understand the long-term effects of hyperbaric oxygen therapy (HBOT). Our goal is to determine whether improvements after treatment are maintained over time and whether additional benefits appear months after treatment has ended. We will evaluate changes in cognitive function, mental health, and daily functioning to help strengthen the scientific evidence supporting the use of HBOT and guide future treatment recommendations.

Conditions treated in intensive care units (ICUs) such as the acute respiratory distress syndrome (ARDS), congestive heart failure, COVID pneumonia, and sepsis are common. These can lead to high rates of depression, anxiety, and PTSD that worsen quality of life. Yet there are few effective strategies able to overcome barriers of limited access to mental health care. Even less is known about the experiences of patients from racially and ethnically minoritized populations because of they haven't been included well in past research. To address this problem, the investigators developed Blueprint, a mobile app that coaches people to use adaptive coping skills to self-manage their symptoms. The investigators found that it reduced depression symptoms and improved quality of life compared to placebo. To confirm these promising findings, the investigators are doing a formal test of Blueprint. The investigators will enroll 400 people who received ICU care from 4 hospitals (Duke, UCLA, Colorado, and Oregon). These patients will be randomized to receive either the Blueprint mobile app or a special Education Program mobile app the investigators developed. -both delivered through similar mobile app platforms. Our specific aims are to see which program improves symptoms better across 6 months of follow up. This project addresses national research priorities and could advance the field with a personalizable yet population-focused therapy that could be scaled broadly and efficiently to enhance mental health equity.

This single-arm clinical intervention study evaluates a 12-session SEE FAR CBT intervention for adults aged 18 years and older with posttraumatic stress disorder (PTSD). SEE FAR CBT is a trauma-focused cognitive-behavioral treatment approach. Participants will complete self-report psychological questionnaires at three time points: baseline, after completion of the intervention, and at a 3-month follow-up. The study aims to examine changes in PTSD symptoms and related psychological outcomes over the course of treatment and follow-up.