A slide from Dr. Charney’s introduction, showing that depression is the leading cause of disability worldwide.
The Department of Psychiatry’s seventh annual symposium took place on Friday, February 8. The speakers covered emerging treatments for depression including ketamine, deep brain stimulation, and personalized treatment.
“This symposium was an opportunity for researchers, clinicians, and individuals from the community to come together to take stock of the magnitude of the problem of depression, and discuss the latest in treatment innovations,” said James Murrough, MD, PhD, who organized and presented at the event. “Despite the large scale problems of depression and suicide in our country, the research presented at the symposium is cause for great optimism. We believe that we will have breakthrough treatments for patients suffering for depression in the near future.”
The Depression and Anxiety Center
Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System, opened the symposium by announcing Mount Sinai’s new Depression and Anxiety Center for Discovery and Treatment (DAC), headed by Dr. Murrough. DAC will build upon its previous iteration, the Mood and Anxiety Disorders Program, via its mission to advance the treatment of depression, anxiety, and related disorders through innovative clinical and translational research, and to provide exceptional evidence-based clinical care to patients.
“To come up with a breakthrough is not easy—to do so requires intelligence that involves not just memory, but creativity,” Dr. Charney said. “There are only a few places in the country that have the resources and scientists that make discoveries that change the lives of patients, and we’re fortunate to have that here at Mount Sinai.”
Stress and epigenetics
The first keynote was delivered by Bruce McEwen, PhD, of The Rockefeller University, on the role of stress and epigenetics in the causes and treatment of depression. Epigenetics refers to the study of differences in gene expression that come as a result of environmental factors throughout the course of an individual’s life. Experiences change the brain, and a history of chronic stress can alter the brain’s physical structure. Dr. McEwen said that “gene expression is a one-way street, and we can’t turn back the clock; we must focus on resilience and redirection, as opposed to reversal.”
Translational neuroscience driving novel antidepressant development
Dr. Murrough moderated the first panel: Scott Russo, PhD, on immune mechanisms, Ming Hu Han, PhD, on hyperpolarization-activated cyclic nucleotide-gated (HCN) channel targets, and Gerard Sanacora, MD, PhD, from the Yale School of Medicine, on glutamate and GABA.
Dr. Russo discussed his research into how the immune system plays a causal role in stress vulnerability, specifically the pro-inflammatory cytokine interleukin 6. He showed that individual differences in the inflammatory response to stress can lead to social avoidance in animal models, and he is investigating these differences. Similarly, Dr. Han is exploring why some people are stable after experiencing stress and others are not, and his lab is exploring HCN channels for potential drug discovery, as HCN channels are involved in mediating ketamine effects. Dr. Sanacora discussed how glutamate and GABA contribute to depression on the molecular and cellular level. He highlighted a new drug in development, brexanolone, that binds to the GABA receptor, as well as various ketamine studies.
Biosignatures for personalized treatment
Madhukar Trivedi, MD, from UT Southwestern Medical Center, presented the second keynote talk on biomarkers for diagnostic purposes.
“We need to look at the interaction of an array of clinical, EEG, neuroimaging, and serum markers,” he said. “This approach can lead to customized treatments for individuals.” His research underscores the importance of tracking physiological biomarkers based on neuroimaging, neurophysiology, genomics, proteomics, and metabolomics measures to understand depressive symptoms and treatment effects.
Therapeutic innovations for treatment resistant depression
Manish Jha, MD, moderated the second panel: Dr. Murrough on rapidly acting antidepressants including ketamine, Corey Keller, MD, PhD, of Stanford, on the mechanisms of antidepressant response to transcranial magnetic stimulation (TMS), and Helen Mayberg, MD, on deep brain stimulation (DBS).
Dr. Murrough brought the backstory on ketamine as the first drug to show rapid antidepressant effects within hours, and noted that Mount Sinai conducted the first experiments on repeated dosing, the first study of intranasal ketamine, and the first randomized controlled trial of ketamine for suicidal ideation. Dr. Keller discussed his aims for maximizing clinical response to TMS by enhancing specificity and plasticity. Regarding “metaplasticity,” he notes that “previously induced plasticity can modify a synapse’s ability to induce future plasticity,” and hopes to use computational models to predict changes in the brain. Dr. Mayberg spoke about her DBS work, which involves implanting electrodes into the subcallosal cingulate near the center of the brains of patients whose depression “couldn’t be drugged down, talked down, or shocked down with ECT.” Her pioneering work takes place in collaboration with other Mount Sinai researchers at the new Center for Advanced Therapeutics.
A slide from Dr. Murrough’s presentation.
Take-home message
The consensus? When you make a change, you create a new version of the brain. “The brain is flexible and plastic, which is cause for great optimism in the future of treating depression.”
This symposium was made possible thanks to a generous gift from Dr. Karen Davis and the Elkins Foundation.