The Anne and Joel Ehrenkranz Laboratory for the Study of Human Resilience performs promising research in areas such as depression and post-traumatic stress disorder (PTSD). Our research team is working to understand what constitutes human biological and psychological resilience and how to translate this understanding into more effective therapies to improve patient outcomes. Over the years we have made meaningful strides, identifying new targets for treatments, and testing the efficacy of therapeutic interventions.
A significant element of our research program centers on identifying potential targets for drug discovery efforts. As we enhance our understanding of the mechanisms of depression and resilience, we are better positioned to determine new ways of disrupting or counteracting those systems. The team is also developing innovative therapeutic approaches to make treatments more accessible and effective, and to alleviate common barriers or challenges.
Ketamine, which acts as a selective N-Methyl-D-aspartic acid receptor antagonist, has shown tremendous promise as a therapeutic agent for treating depression, and more recently in PTSD. In March 2019, the U.S. Food and Drug Administration approved intranasal esketamine—a form of ketamine marketed as SPRAVATO™ CIII Nasal Spray*— to treat patients with treatment-resistant depression. Broadly considered one of the most important developments in the field of depression research, ketamine can trigger a rapid, robust antidepressant effect in patients. The Ehrenkranz Laboratory is engaged in several studies to better understand how ketamine works and how to maximize its clinical benefit.
The team is exploring the therapeutic potential of neuropeptide Y (NPY), a key molecule found in the brain that mediates anxiety and fear. Mount Sinai conducted the first in-human study of intranasal NPY in patients with PTSD. Building on these findings, the team is designing additional studies to understand how the drug may work and how it can be optimized for the best patient outcomes.
and his team tested the drug’s efficacy in treating depression in humans for the first time. They found that it led to improvement in symptoms of depression and anhedonia in patients with major depressive disorder in the context of an open-label design.
Mount Sinai researchers are also investigating how to harness the power of technology to improve resilience and create innovative treatment options for patients with depression and mood disorders. Our team developed the first digital, online cognitive emotional training (CET) program for depression. Since access to care is often an obstacle for patients suffering from depression, this advancement holds the potential to transform how depression is treated. We recently completed a randomized, controlled trial to confirm the efficacy of this program, and investigators are now implementing an internet-based form of CET—called iCET—that will enable patients to easily and conveniently receive computerized treatment for depression from the comfort of their own homes.
Our lab developed and validated a novel method to visualize the locus coeruleus (LC), a tiny structure in the brain critical to how humans respond to fear, threat, and stress. The LC likely plays a key role in resilience and distress following trauma, and this is the first time scientists have visualized it in humans. After two years of development, Dr. Murrough and his team showed not only that the LC can be reliably visualized in patients, but also that patients with PTSD or anxiety disorders also exhibit abnormalities in the LC. This led to a five-year R01 National Institutes of Health grant to investigate the LC’s role in trauma and resilience. It is the first transdiagnostic in vivo study of LC in anxiety, and it aims to enhance diagnostic methods for anxiety disorders and identify novel targets in the LC for creating new therapies.
*Mount Sinai was involved in the research that led to the development of this new treatment method for treatment-resistant depression and receives financial remuneration from the manufacturer of SPRAVATO. Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, is a co-inventor of patents related to this new treatment method and as such receives remuneration through Mount Sinai from the manufacturer. For more information about these financial interests and Mount Sinai’s leadership role in SPRAVATO, please visit bit.ly/esketamine-development. (Dr. Murrough does not have a financial interest in SPRAVATO.)