Neuroendocrine, Epigenetic, and Novel Treatments for PTSD
WELCOME TO THE YEHUDA LAB
The Yehuda Lab is a multidisciplinary research team with a strong foundation in applied basic, clinical and translational research. The lab investigates a wide range of endocrine, molecular, and brain biomarkers for PTSD and resilience, and has been at the forefront of investigations of epigenetic me chanisms associated with intergenerational trauma in populations such as offspring of Holocaust survivors and babies born to mothers exposed to the World Trade Center attack on 9/11. To better understand gene-environment interactions associated with PTSD risk, the Yehuda lab has recently pioneered the use of stress-stimulated induced neurons, using stem cell technology. These studies have led to the development of novel treatment approaches including psychotherapy augmentation and PTSD prevention strategies. More recently, the Yehuda lab launched the Center for Psychedelic Psychotherapy and Trauma at Mount Sinai. In addition to clinical studies, the Yehuda lab also performs animal studies to further examine underlying mechanisms associated with trauma exposure. The Yehuda lab is physically located at the James J. Peters Veterans Affairs Medical Center (JJP VAMC), an affiliate of the Icahn School of Medicine at Mount Sinai.
Bierer LM, Bader HN, Daskalakis NP, Lehrner A, Provençal N, Wiechmann T, Klengel T, Makotkine I, Binder EB, Yehuda R. Intergenerational Effects of Maternal Holocaust Exposure on FKBP5 Methylation. Am J Psychiatry. 2020 Aug 1;177(8):744-753. doi: 10.1176/appi.ajp.2019.19060618. Epub 2020 Apr 21. PubMed PMID: 32312110.
Somvanshi PR, Mellon SH, Yehuda R, Flory JD, Makotkine I, Bierer L, Marmar C, Jett M, Doyle FJ 3rd. Role of enhanced glucocorticoid receptor sensitivity in inflammation in PTSD: insights from computational model for circadian-neuroendocrine-immune interactions. Am J Physiol Endocrinol Metab. 2020 Jul 1;319(1):E48-E66. doi: 10.1152/ajpendo.00398.2019. Epub 2020 Apr 21. PubMed PMID: 32315214.
Yang R, Wu GWY, Verhoeven JE, Gautam A, Reus VI, Kang JI, Flory JD, Abu-Amara D, Hood L, Doyle FJ 3rd, Yehuda R, Marmar CR, Jett M, Hammamieh R, Mellon SH, Wolkowitz OM. A DNA methylation clock associated with age-related illnesses and mortality is accelerated in men with combat PTSD. Mol Psychiatry. 2020 May 7;. doi: 10.1038/s41380-020-0755-z. [Epub ahead of print] PubMed PMID: 32382136.
Sher L, Bierer LM, Flory J, Hill MN, Makotkine I, Yehuda R. Endogenous cannabinoid levels and suicidality in combat veterans. Psychiatry Res. 2020 May;287:112495. doi: 10.1016/j.psychres.2019.112495. Epub 2019 Jul 25. PubMed PMID: 31375282.
Dalvie S, Maihofer AX, Coleman JRI, Bradley B, Breen G, Brick LA, Chen CY, Choi KW, Duncan LE, Guffanti G, Haas M, Harnal S, Liberzon I, Nugent NR, Provost AC, Ressler KJ, Torres K, Amstadter AB, Bryn Austin S, Baker DG, Bolger EA, Bryant RA, Calabrese JR, Delahanty DL, Farrer LA, Feeny NC, Flory JD, Forbes D, Galea S, Gautam A, Gelernter J, Hammamieh R, Jett M, Junglen AG, Kaufman ML, Kessler RC, Khan A, Kranzler HR, Lebois LAM, Marmar C, Mavissakalian MR, McFarlane A, Donnell MO, Orcutt HK, Pietrzak RH, Risbrough VB, Roberts AL, Rothbaum AO, Roy-Byrne P, Ruggiero K, Seligowski AV, Sheerin CM, Silove D, Smoller JW, Stein MB, Teicher MH, Ursano RJ, Van Hooff M, Winternitz S, Wolff JD, Yehuda R, Zhao H, Zoellner LA, Stein DJ, Koenen KC, Nievergelt CM. Genomic influences on self-reported childhood maltreatment. Transl Psychiatry. 2020 Jan 27;10(1):38. doi: 10.1038/s41398-020-0706-0. PubMed PMID: 32066696; PubMed Central PMCID: PMC7026037.
Bersani FS, Mellon SH, Lindqvist D, Kang JI, Rampersaud R, Somvanshi PR, Doyle FJ, Hammamieh R, Jett M, Yehuda R, Marmar CR, Wolkowitz OM. Novel Pharmacological Targets for Combat PTSD-Metabolism, Inflammation, The Gut Microbiome, and Mitochondrial Dysfunction. Mil Med. 2020 Jan 7;185(Suppl 1):311-318. doi: 10.1093/milmed/usz260. PubMed PMID: 32074311.
Breen MS, Bierer LM, Daskalakis NP, Bader HN, Makotkine I, Chattopadhyay M, Xu C, Grice AB, Tocheva AS, Flory JD, Buxbaum JD, Meaney MJ, Brennand K, Yehuda R. Correction: Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development. Transl Psychiatry. 2020 Jan 6;10(1):1. doi: 10.1038/s41398-019-0665-5. PubMed PMID: 32066695; PubMed Central PMCID: PMC7026151.
Vermetten E, Yehuda R. MDMA-assisted psychotherapy for posttraumatic stress disorder: A promising novel approach to treatment. Neuropsychopharmacology. 2020 Jan;45(1):231-232. doi: 10.1038/s41386-019-0482-9. Epub 2019 Aug 27. PubMed PMID: 31455855; PubMed Central PMCID: PMC6879520.
Somvanshi PR, Mellon SH, Flory JD, Abu-Amara D, Wolkowitz OM, Yehuda R, Jett M, Hood L, Marmar C, Doyle FJ 3rd. Mechanistic inferences on metabolic dysfunction in posttraumatic stress disorder from an integrated model and multiomic analysis: role of glucocorticoid receptor sensitivity. Am J Physiol Endocrinol Metab. 2019 Nov 1;317(5):E879-E898. doi: 10.1152/ajpendo.00065.2019. Epub 2019 Jul 19. PubMed PMID: 31322414; PubMed Central PMCID: PMC6879860.
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
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
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.
Meet the Director
Rachel Yehuda, PhD
Rachel Yehuda joined the Psychiatry Department in 1991, and has been a tenured professor at the Icahn School of Medicine at Mount Sinai (ISMMS) for over 20 years with a demonstrated record of successful and productive research projects. She received her Ph.D. at the University ofMassachusetts at Amherst, MA and completed post-doctoral work at Yale Medical School. Dr. Yehuda is the Mental Health Patient Care Center Director and Director of the Laboratory of Clinical Neuroendocrinology and Neurochemistry at the James J. Peters VAMC, and has recently been appointed as Vice Chair for the Veterans Affairs in the Psychiatry Department. Her expertise is in the study the enduring effects of trauma exposure, particularly PTSD, as well as associations between biological and psychological measures. Throughout her career she has been interested in the role of hormones and other molecular and brain processes in producing vulnerability and resilience to trauma exposure. She has received numerous grants from the National Institute of Mental Health, the Department of Defense, the Veterans Administration and various Foundations such as Lightfighter Trust, The American Foundation for Suicide Prevention, and the Brain and Behavior Research Foundation. These grants have allowed the Yehuda lab to innovate in areas of molecular biology and treatment of PTSD, identification of risk and resilience, an intergenerational transmission of trauma effects. Dr. Yehuda’s laboratory has produced more than 400 peer-reviewed publications from previous projects as well as over 10 edited volumes. Her work has been featured in several documentaries and lay media.
In the News
APA Film: Center for Psychedelic Psychotherapy & Trauma Research at Icahn School of Medicine at Mount Sinai
EntheoGeneration. 2019 Burning Man Psychedelic Speaker Series. Click here to watch Dr. Yehuda demystify psychedelic research.
MOUNT SINAI. 30 Years on the Forefront of Trauma Research
The Gland Grant Trio performing at the reception of the 2012 Annual Meeting of the International Society of Psychoneuroendocrinology (ISPNE). Check out Dr. Yehuda singing her humorous ““The Grant Song (Nobody Quotes You)” original melody.
SPOTIFY. INbodied Life with Lauren Taus: Treating Trauma with Dr. Rachel Yehuda. A Conversation on Intergenerational Trauma, Epigenetics, Psychedelic Therapy, Post-Traumatic Grow and Now. Click here to listen to podcast episode.
Watch Dr. Yehuda discuss psychedelic medicine on Neuroscience with Bessel van der Kolk .
Freakonomics Radio. From Party to Prescription: How Psychedelics are Changing Traditional Psychiatry. Podcast Mixtape. Watch here as Freakonomics Radio’s Stephen Dubner, Dr. Rachel Yehuda and other leading neuroscientists discuss psychedelics and other historically illicit drugs as potential alternative therapies for psychiatric illnesses such has PTSD, addition and depression.
We are currently seeking qualified data managers, post-doctoral fellows, and clinical research coordinators. If you are interested in joining our team, please send us an email, telling us a bit about yourself and the position that you are interested in.
James J. Peters Veterans Affairs Medical Center
130 W Kingsbridge Road Bronx, NY 10468
Icahn School of Medicine at Mount Sinai
1 Gustave L. Levy Pl
New York, NY 10029