CURRENT GRANT FUNDING & AWARDS

A Phase 2 Open-Label, Randomized Comparative Effectiveness Study for MDMA-Assisted Psychotherapy in U.S. Military Veterans with Chronic PTSD
PI:  Rachel Yehuda
Multidisciplinary Association for Psychedelic Studies (MAPS)

MDMA-assisted psychotherapy for PTSD is a highly promising, innovative treatment that is currently in Phase III trials and has been granted breakthrough status by the FDA. This study will assess the relative effectiveness of two versus three active MDMA sessions during the course of psychotherapy, which has important implications for identifying and promoting the most cost-effective treatment for veterans with PTSD. This study will also generate important data regarding the efficacy of this cutting-edge therapy for treatment seeking veterans with PTSD in VA outpatient clinics.

RNA Expression in PTSD in Induced Human Neurons and Blood Cells in Basal and Glucocorticoid-Stimulated Conditions
PI: Rachel Yehuda
Department of the Army- USAMRAA

The aim of this study is to use a new method to induce neuronal cells (iNeurons) from skin cells in combat veterans with and without PTSD and assess RNA expression in these cells and in peripheral blood mononuclear cells (PBMCs) from the same veterans. The overarching hypothesis is that we can identify PTSD molecular pathways in both iNeurons and PBMCs that would (a) be impacted by glucocorticoids and (b) overlap with comparable pathways detected in our blood biomarkers human studies and in blood and brain of animals with PTSD-like phenotypes.

Evaluation of Prognostic and Diagnostic PTSD Biomarkers
PI: Rachel Yehuda
Department of the Army- USAMRAA

The primary goal of this project is to support the collection of epigenetic and other molecular biomarkers in OEF/OIF combat veterans undergoing CPT-C psychotherapy and resilient controls. This study will also aim to discover and validate markers, pathways, and networks associated with the prognosis of PTSD following treatment and the state/severity of PTSD.  It will also validate biological correlates of PTSD risk and determine which, if any, of these markers improve with recovery while also identifying biomarkers that emerge post-treatment in association with recovery.

Evaluation of Glucocorticoid-Related Prognostic and Diagnostic PTSD Biomarkers
PI: Rachel Yehuda
VA ORD Merit

This project is designed to investigate genetic, epigenetic, gene expression and neuroendocrine differences between combat veterans who no longer meet criteria for PTSD following psychotherapy and those who retain the diagnosis post-treatment. It will also compare the biology of similarly exposed veterans who did not develop PTSD with those who recover following treatment, in order to identify biological systems that are activated in recovery.

PTSD Prevention Using Oral Hydrocortisone in the Immediate Aftermath of Trauma
PI: Rachel Yehuda
Department of the Army – USAMRAA

This project proposes to test a one-time prophylactic treatment for the prevention of symptoms of PTSD and related mental health disturbances and the promotion of resilience using a single dose of hydrocortisone (HCORT), administered within six hours of trauma exposure. The main aim of the study is to determine whether early intervention with a single dose of HCORT, compared to placebo, administered within several hours following trauma exposure, will reduce the risk of developing PTSD in trauma survivors displaying distress, panic, anxiety or dissociation in the emergency room. The information obtained will be relevant to enhancing resilience post-trauma in both military and civilian trauma. If successful, the study will introduce an important, inexpensive, portable, safe and effective tool for combat veterans to carry with them during a critical incident.

Neuroimaging Biomarkers of Resilience and Treatment Response in PTSD
PI: Rachel Yehuda
Brain and Behavior Research Foundation

The specific aims of this project are (1) to identify neural circuits associated with resilience to trauma using multimodal imaging; (2) to identify multimodal neuroimaging biomarkers of treatment response to CPT-C in PTSD; and (3) exploratory aims will investigate the relationship between neuroimaging measures and biological measures available from the parent study including: methylation, gene expression, lysozyme IC50-DEX, and plasma NPY.

Systems Biology Consortium Project
Site PI: Rachel Yehuda
Department of Defense (DoD)

This project is an ongoing effort to perform analyses of endocrine and resilience biomarkers and analyze other biological data from blood samples and clinical information already collected from The Fort Campbell Cohort Study for objective diagnosis of Post-Traumatic Stress Disorder (PTSD), depression, and Traumatic Brain Injury (TBI). The investigative team proposes that panel of specific brain proteins and miRNAs, specific transcriptomic and epigenomic markers to obtained prior to deployment, along with the neuroendocrine and reliance related data will predict PTSD. It also predicts that the presence of specific endocrine and resilience related markers will be associated with presence or absence and levels of symptoms prior to deployment. As such, tools for prognosis and diagnosis that are objective, and blood based can be developed. 

A Novel Posttraumatic Stress Disorder Treatment for Veterans with Moral Injury Study
Site PI: Amy Lehner
VA Office of Research and Development

The objective of this project is to test the efficacy of an individual treatment for post-traumatic stress disorder (PTSD) stemming from moral injury called Impact of Killing (IOK), compared to a present-centered therapy (PCT) control condition, and to determine the rehabilitative utility of IOK for Veterans with PTSD. The study aims to test whether IOK can help improve psychosocial functioning for Veterans, as well as PTSD symptoms and determine whether IOK gains made by Veterans in treatment are durable. IOK is a treatment that can be provided following existing PTSD treatments, filling a critical gap for Veterans with moral injury who continue to suffer from mental health symptoms and functional difficulties.

Biological and Psychological Correlates of Sexual Dysfunction in PTSD
PI: Amy Lehrner
VA Career Development Award

The proposed study employs a mixed-method, cross-sectional design to investigate biological and psychological correlates of sexual dysfunction in male OEF/OIF/OND combat veterans. Specifically, this investigation will assess distinct components of sexual dysfunction (e.g., lack of desire, problems with performance and consummation) and their associations with PTSD symptoms and severity and with endocrine markers, including catecholamines (epinephrine, norepinephrine, dopamine) and glucocorticoid sensitivity, that are implicated in PTSD. The information generated from this study will provide the necessary foundation for the development of a new intervention targeting sexual dysfunction in PTSD. Such an intervention has the potential to strengthen relationships and promote recovery from PTSD.

Cognitive and Neural Mechanisms of the Accelerated Aging Phenotype in PTSD
Subcontract PI: Rachel Yehuda, PI: Bret Rutherford
NIH/ NIMH

This project aims to elucidate the complex interactions between PTSD and aging processes that culminate in poor health outcomes for older adults. The primary focus is to determine whether alterations in brain structure, function, and connectivity lead to premature cognitive decline in older PTSD patients.

Glucocorticoid Functioning in OEF/OIF/OND Veterans with mTBI and PTSD
PI: Janine Flory
VA MERIT CSR&D

The goal of this project is to enhance coordination of diagnosis and treatment of combat veterans who receive care at VA. The study will examine glucocorticoid (GC) functioning in PTSD and mTBI in order to determine whether people with both conditions show a neuroendocrine profile (i.e., GC sensitivity) that resembles that observed in people with PTSD alone. The primary study outcomes will include an assessment of hypothalamic-pituitary-adrenal (HPA) axis functioning (i.e.,24 hour urinary cortisol, cortisol (CORT) and adrenocorticotrophin (ACTH) response to dexamethasone (DEX), lysozyme IC50-DEX) and the CORT and ACTH response to glucocorticoid ingestion [i.e., glucocorticoid challenge test (GCT)]. Secondary measures include cognitive testing following the GCT.

Predicting Suicidal Behavior in Veterans with Bipolar Disorder Using Behavioral and Neuroimaging Based Impulsivity Phenotypes
PI: Philip Szeszko
VA MERIT

This project aims to investigate two neural circuits taping state measures of rapid response inhibition and choice impulsivity, respectively, using functional magnetic resonance imaging to predict suicidal behavior longitudinally over one year in veterans with bipolar disorder This study will also investigate novel measures of crossing white matter fiber arrangement comprising these circuits and their relationship to impulsivity.