Hot on the Trail: Schizophrenia

On April 23, Dolores Malaspina, MD, MS, MSPH, published results of a study on marriage duration and how it affects schizophrenia risk in offspring. She found that if a specific man and a woman had a shorter duration of sexual contact before conception, their child would be at a higher risk of developing schizophrenia. The authors write that “offspring born to parents married fewer than two years, equivalent to about one year of pre-pregnancy sexual contact, had a 50 percent increase in risk for schizophrenia.” Children from marriages of 2-4 years had a 30 percent increase in risk.

Marriage duration is not typically indicative of duration of sexual contact; however, this analysis was performed on the children of the 1964-1976 Jerusalem Perinatal Cohort Schizophrenia Study, and the records show that 97 percent of them were born to married couples. At that time, Israel had one of the lowest worldwide rates of out-of-wedlock births, so marriage duration in this population is a reasonable proxy for sexual contact.

Dr. Malaspina has been a psychiatrist for 30 years, and has 300 publications under her belt.

This marriage duration risk factor is independent of established risk factors such as family history of psychiatric disorders and the father’s age at the time of conception. Accounting for the duration of the couple’s sexual contact magnifies the effect of paternal age on offspring risk for schizophrenia, and both factors together explain any effect of later paternal age at marriage. “When older men get married, they are more likely to have babies right away. This could mean that the father’s age at marriage is not a causal factor,” said Dr. Malaspina.

The shorter periods of sexual contact before conception also increase the risk for preeclampsia, a complication during pregnancy that includes high blood pressure, swelling, and high urine protein levels. Dr. Malaspina theorizes that the risk pathway for preeclampsia, which includes prenatal immune activation, could increase the risk for inflammatory conditions such as schizophrenia in offspring. She is working on replicating these findings in other cohorts, and anticipates being able to test if the pathways to schizophrenia include prenatal immune activation.

This is just the latest finding in Dr. Malaspina’s expansive career, which has spanned genetics, zoology, epidemiology, and more. Rather than looking at just symptoms and behavior, her research involves examining the larger picture of the disease, including associated metabolic diseases, physical biomarkers, and gene mutations. She has a track record of thinking outside the box and fostering interdisciplinary collaboration to find pathways to severe mental illnesses, especially schizophrenia. “It’s working across boundaries that really invigorates progress,” she says.

Dr. Malaspina’s particular interest in schizophrenia has to do with the fact that the illness “fundamentally impairs the ability to function—it interferes with social signaling and group selection.” It also comes from her personal experience. She has been on a lifelong quest to understand the underlying factors of schizophrenia ever since her sister, Eileen, was diagnosed in 1971.

The beginning

Her sister’s grades started to slip in her senior year of high school, and she became increasingly paranoid that the neighbors were talking about her and that helicopters were monitoring her activities. She was unable to eat or sleep, and in a constant state of terror. Her family took her to the hospital, where she was diagnosed with schizophrenia. At that time, psychiatrists often blamed the “schizophrenogenic mother” for the disease, meaning that a mother’s cold, domineering, and manipulative personality triggered distrust, resentfulness, and psychosis in her child. This blame on Dr. Malaspina’s mother heaped immense guilt onto her already grieving and distressed family. Deeply affected by this experience, Dr. Malaspina decided to become a scientist and psychiatrist and to devote her career to getting to the bottom of the true causes of this disease.

Career trajectory

She wasted no time. Dr. Malaspina got her MS in zoology and then her MD at Rutgers University. She completed a residency in psychiatry and a clinical research fellowship at Columbia University Medical Center, and at the end of her residency transitioned to independent investigator. Two years later, she was named founding chief of the Schizophrenia Research Unit at the New York State Psychiatric Institute. She stayed at Columbia for 22 years, covering all academic levels: chief resident, research fellow, assistant professor, associate professor, and full professor. In 1998, she received her MS in public health of epidemiology at Columbia. In 2006, she moved to NYU to become the Chair of the Department of Psychiatry, where she founded and directed the Institute of Social and Psychiatric Initiatives (InSPIRES), a multidisciplinary research program.

Breakthroughs

Dr. Malaspina has received nearly continuous NIMH funding throughout her career, and has a collection of scientific discoveries under her belt. She was the first to demonstrate that paternal aging is a predictor of schizophrenia, which has been replicated worldwide. “Some people said it’s just that older men are carrying more genetic risk for schizophrenia, which delayed their childbearing and explains the increased risk of the disease for their offspring,” she said. Her pioneering work on higher paternal age and its correlation with schizophrenia risk stimulated hundreds of follow-up studies confirming the findings, and her new study confirms that older paternal age at marriage is not a risk factor.

Dr. Malaspina also showed hippocampal inflammation in those with schizophrenia, and that olfaction, or the sense of smell, is related to social function. She defined four versions of schizophrenia via gene analysis, showing each subtype had a discrete presentation. She also looked at the effects of the Six Day  War of 1967 on pregnancies, and discovered that early pregnancy trauma was a risk factor for schizophrenia in females.

Moving to Mount Sinai

In 2017, Dr. Malaspina moved to Mount Sinai and is now director of the psychosis program Critical Connections. Why Mount Sinai? “The leadership in other institutions is not as aware of the amazing impact that psychiatric disorders have on society,” she said. “I love that Mount Sinai cuts across molecular science, epidemiology, clinical trials, outcomes, and research, and the sheer size and number of scientists working here makes it really special. Also, the new chair, René Kahn, MD, PhD, himself an impressive schizophrenia researcher, had recruited a group of accomplished schizophrenia experts, so it was a wonderful opportunity to work with them.”  She adds that Mount Sinai has a fantastic burgeoning genetics department, which is a critical component of her own research. “I hope that we are close to defining specific different pathways to schizophrenia that can lead to precise treatments to prevent and cure the disease, rather than our current ‘one size fits all’ treatment approaches,” she said.

Dr. Malaspina is Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, where she is also the Director of the Critical Connections Psychosis Program in collaboration with the Nash Family Department of Neuroscience and the Division of Psychiatric Genomics. Her MS is in zoology, and her MSPH is in epidemiology. 

 

30 Years on the Forefront of Trauma Research

Dr. Yehuda in Burlington, Vermont, where she was giving a talk about molecular markers of suicide risk in returning veterans.

In January, Rachel Yehuda, MS, PhD, was in Israel learning how to use MDMA-assisted psychotherapy to treat PTSD. MDMA, sometimes known as ecstasy, is poised to become a powerful treatment option for PTSD. In 2017, the U.S. Food and Drug Administration designated it as a breakthrough therapy when coupled with psychotherapy sessions that last up to eight hours. The results of preliminary clinical studies are promising, and the drug could be approved by the FDA by 2021.

To prepare the caregivers who will be administering it, the Multidisciplinary Association for Psychedelic Studies has been holding MDMA therapy training programs, such as the one Dr. Yehuda attended in Israel. As part of the training, the therapists themselves undergo MDMA-assisted psychotherapy. Dr. Yehuda’s goal is for the James J. Peters VA Medical Center in the Bronx (which is affiliated with Mount Sinai), where she is the Mental Health Patient Care Center Director, to be the first VA medical center to offer this treatment to veterans. She is also planning to investigate the mechanisms of this treatment by evaluating genomic and molecular biomarkers before and after treatment, as she has been doing with other pharmacological and psychotherapy treatments for PTSD.

“MDMA produces a substantial change in mental state that increases people’s ability to engage with traumatic material in psychotherapy,” she said. “This is important because it is easy for trauma survivors to avoid their feelings of shame, vulnerability, fear, and guilt. Because this treatment seems to work so well, studying dysregulated molecules and pathways before and after MDMA therapy may help us understand more about how resilience is achieved from a neurochemical perspective.”

This is only the latest example of Dr. Yehuda being on the cutting edge of trauma treatment. She has spent her career far ahead of the curve in PTSD, anticipating the use of biological markers for diagnosis, prognosis, and treatment-matching. Her work has also been at the forefront of identifying molecular processes involved in PTSD risk, susceptibility, resilience, and recovery.

The beginning

Dr. Yehuda started her career as a postdoctoral fellow in biological psychology at Yale Medical School in 1987. Her dissertation focused on how stress hormones regulated important developmental brain processes in animal models, but she was curious about the applicability in humans. Her postdoctoral work produced some of the initial findings on the endocrinology and neurochemistry of PTSD, and as a new assistant professor at Mount Sinai in 1991, she led a group that was among the first to look at specific biological differences in people who have survived trauma and have PTSD.

Dr. Yehuda and her colleagues observed that Vietnam War combat veterans with PTSD had significantly lower levels of cortisol, a steroid hormone that helps regulate physiological responses to stress, compared to people without PTSD. This finding was provocative because elevated cortisol levels are associated with stress, and it seemed counterintuitive for cortisol levels to be decreased in those suffering from PTSD. This discovery was the first step towards understanding that PTSD involves a failure to recover from normal processes involved in responding to stress, and helped identify targets for prevention and treatment.

Towards the end of her postdoctoral fellowship, Dr. Yehuda became interested in whether the observations made about combat Vietnam veterans could be applied more generally to other groups of trauma survivors, so she decided to initiate biological studies in Holocaust survivors. Dr. Yehuda had known many Holocaust survivors growing up in the Jewish community in Cleveland. At first glance, they did not seem to have similar psychological or behavioral issues to combat veterans from the Vietnam War.

As a pilot study, Dr. Yehuda brought a research group to Cleveland and set up a lab in her parents’ basement. The team interviewed approximately 100 Holocaust survivors and obtained urine and blood samples to determine stress hormone levels. They were surprised to learn that about half of those interviewed had PTSD, and also demonstrated lower cortisol levels—similar to what had been observed with the Vietnam veterans. An important difference, however, was that Holocaust survivors typically weren’t treatment-seeking, and they didn’t have a dedicated institution like the VA. To rectify this, Dr. Yehuda started a Holocaust treatment clinic at The Mount Sinai Hospital in 1992 to treat survivors and their offspring.

A key to prevention

The cortisol findings shaped the trajectory of the rest of Dr. Yehuda’s career. Her work over the years shows that in people with PTSD, cortisol levels don’t increase the way they should to counteract adrenaline and calm the body, which is what leads to resilience and recovery.

Finding a way to increase cortisol could be a method to prevent PTSD, and Dr. Yehuda has been investigating options. The Icahn School of Medicine at Mount Sinai has one of the largest programs in the country for the study of PTSD biomarkers, and funding to further her research has brought in approximately $12 million over the last decade. She anticipates an award notice for an almost $6 million grant from the Department of Defense in April for a study that provides trauma patients in hospital emergency rooms with an injection of synthetic cortisol, to mimic the body’s calming system and prevent PTSD. If it works, the potential for soldiers to self-administer on the battlefield would be game-changing.

She’s also working with combat veterans in collaboration with the New York Stem Cell Foundation to examine molecular aspects of PTSD. The study involves converting fibroblasts from skin into induced pluripotent stem cells, then reprogramming them into neurons and stimulating the neurons with stress hormones to see whether response to stress hormones is genetically predetermined.

A new finding on the effects of trauma on the next generation

In 2016, Dr. Yehuda published results of a study showing that Holocaust survivors and their adult offspring had epigenetic changes on the same region of a stress-related gene. Epigenetics has been described as the software that directs the body’s hardware (genes)—changes caused by modified gene expressions as opposed to changing the genes themselves.

This finding was the latest discovery in what had been a 25-year examination of the effects of the Holocaust on their offspring. The research began when adult children of Holocaust survivors called the Mount Sinai Specialized Treatment Program for Holocaust Survivors asking to be treated. A series of studies demonstrated that Holocaust offspring had several psychological and endocrine findings in association with maternal and paternal Holocaust exposure and PTSD.

In this latest study, Dr. Yehuda reported altered methylation on a gene known as FKBP5 in both Holocaust survivors and their own children: this constituted the first demonstration of a link between parental trauma and offspring effects. The finding was a natural extension of prior work examining effects on offspring in women who were pregnant while exposed to the 9/11 attacks. As she said on the On Being podcast, “We learned that there was a trimester effect on cortisol levels in the babies. That was really huge for us, because we began to understand that some of the differences between maternal and paternal trauma and risk might have to do with in-utero contributions to changing the stress system.”

Veterans’ therapy: Thinking outside the box 

Last year, Dr. Yehuda got a veterans film-making workshop series off the ground in collaboration with the Patton Veterans Project at the James J. Peters VA Medical Center in the Bronx. The workshops serve as a therapeutic tool to empower veterans to contemplate their experiences and work collaboratively to create short films about their time serving and/or reintegration upon returning.

“I’m fascinated with film-making and applying it to veterans because I think storytelling can be essential for healing,” she said. “In fact, the existing therapies for PTSD really are rooted in the idea of telling one’s story. When you make a film, you’re telling the story from the perspective of how the viewer will receive it. And this kind of rotating from different angles and thinking of trauma in a different way is an important part of the therapeutic process. The trauma itself is no longer the end of the story—the story moves, and you move with it. Writing can do this, acting in a play, music—the so-called right-brain type of expressions.”

These examples are just a selection of Dr. Yehuda’s groundbreaking research on trauma—why it happens, how we can prevent it, and how we can treat it. “What all the studies point to is that life events have transformative powers on our biology and behavior,” she said. “By understanding how experience changes us, we can harness that knowledge towards achieving resilience.”

Dr. Yehuda is Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai, where she is also the Vice Chair for Veterans Affairs in the Department of Psychiatry as well as Director of the Traumatic Stress Studies Division. This division includes the PTSD Clinical Research Program and the Neurochemistry and Neuroendocrinology Lab at the James J. Peters Veterans Affairs Medical Center in the Bronx. Her PhD is in psychology and neurochemistry, and her MS is in biological psychology. 

 

Changing the Paradigm for Patients With Treatment-Resistant Depression

Dennis S. Charney, MD

The U.S. Food and Drug Administration on March 5 approved SPRAVATO™ (esketamine) CIII nasal spray for the treatment of treatment-resistant depression. Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, is a co-inventor of a method of treatment, which is patented and part of the drug application for SPRAVATO, a product of the Janssen Pharmaceutical Companies of Johnson & Johnson.

“As a researcher, you strive to come up with new treatments for the patient, especially in terms of finding answers to the most debilitating diseases,” says Dr. Charney, who is also President for Academic Affairs, Mount Sinai Health System. “To know that you oversaw the early development of an approach that can make a difference in the lives of countless individuals is extremely rewarding.”

Esketamine represents the first new mechanism of action in decades to treat major depressive disorder. Delivered in the form of a nasal spray, esketamine works differently than the three classes of antidepressants that are currently on the market. The drug works on the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor in the brain. In contrast, widely used antidepressants target different neurotransmitters—serotonin, serotonin and norepinephrine, and norepinephrine and dopamine—and can take weeks or even months to work.

An estimated 30 percent of people who are treated for depression do not respond to therapies. Treatment-resistant depression (TRD) is a devastating disease that is associated with greater morbidity, higher health care costs, and various comorbid conditions.

“We commend Dr. Charney and his colleagues for their work in changing the paradigm for patients with treatment-resistant depression,” says Kenneth L. Davis, MD, President and Chief Executive Officer of the Mount Sinai Health System. “Through his commitment to innovation and science, Dr. Charney has inspired countless researchers to leverage new technologies and create discoveries to benefit the lives of patients around the world—while at the same time leading the Icahn School of Medicine to unparalleled growth and high national rankings.”

In his role as Dean of the Icahn School of Medicine, Dr. Charney says that many younger researchers look to him for advice. “I tell them that in science you’ve got to keep trying, to keep pushing,” he says. “There is a lot to be gained by working in a small group that is engaged in the give and take of scientific interaction. Researchers should understand that failure is going to happen, but they can use that failure as a stepping stone to discovery.”

Conflicts of Interest Disclosure: Dr. Charney is named as co-inventor on patents filed by the Icahn School of Medicine at Mount Sinai (ISMMS) relating to the treatment for treatment-resistant depression, suicidal ideation, and other disorders. ISMMS has entered into a licensing agreement with Janssen Pharmaceuticals, Inc., and it has and will receive payments from Janssen under the license agreement related to these patents for the treatment of treatment-resistant depression and suicidal ideation under this agreement. Consistent with the ISMMS Faculty Handbook, Dr. Charney is entitled to a portion of the payments received by the ISMMS. Since SPRAVATO has received regulatory approval for treatment-resistant depression, ISMMS and thus, through the ISMMS, Dr. Charney will be entitled to additional payments, beyond those already received, under the license agreement.

Consortium Sheds New Light on Brain Disorders

From left: Kristen Brennand, PhD, Associate Professor, Neuroscience, Genetics and Genomic Sciences, and Psychiatry; Prashanth Rajarajan, MD/PhD candidate; and Schahram Akbarian, MD, PhD, Professor, Psychiatry, and Neuroscience.

Reprinted with permission from AAAS.

More than two dozen researchers at the Icahn School of Medicine at Mount Sinai are advancing brain science by mapping the complex molecular underpinnings of autism spectrum disorder, schizophrenia, and bipolar disorder through their work in the National Institute of Mental Health’s (NIMH) PsychENCODE Consortium. Since this work began in 2015, their contributions—and that of their PsychENCODE colleagues from 14 other U.S. institutions—have helped identify several hundred new risk genes for mental disorders. The research has also revealed critical time windows during brain development when these genes can influence the disease process.

In December, the Consortium published its initial findings in 10 studies that appeared in Science, Science Translational Medicine, and Science Advances. The researchers analyzed more than 2,000 postmortem brain samples from people with no psychiatric conditions and those with schizophrenia, autism, and bipolar disorder. They created and then integrated data sets that included information on DNA variations and gene expression for about 32,000 cells from major regions of the brain. Then the investigators employed machine learning to create a predictive model of risk for the psychiatric disorders.

Their seminal findings received an enthusiastic response from the NIMH. “The PsychENCODE project came through,” said Thomas Lehner, PhD, MPH, Director of the Office of Genomic Research Coordination at the NIMH. “We’re at the beginning—I cannot overstate how early we are. But I can confidently say that for the first time we have a beginning of an understanding of the biology—the molecular pathophysiology of mental disorders—of schizophrenia, and bipolar and autism spectrum disorder.”

Unraveling the Complexity of the Human Brain

“Exploring how the human genome is folded and packaged into the nucleus of each of our billions of brain cells was both awe-inspiring and humbling at the same time,” says Prashanth Rajarajan, MD/PhD candidate at the Icahn School of Medicine at Mount Sinai, who was first author on seminal brain research that was published in the December 14, 2018, issue of Science.

The scientific team discovered that early development is associated with major changes in the spatial organization of DNA inside of brain cells. These changes in how the chromosomal material is packed seem to disproportionately affect DNA sequences linked to schizophrenia heritability risk and provide new insights into the genetic causes underlying this disease.

The study, which was conceived and executed at the Icahn School of Medicine, included senior authors Schahram Akbarian, MD, PhD, Professor, Psychiatry, and Neuroscience; and Kristen Brennand, PhD, Associate Professor, Neuroscience, Genetics and Genomic Sciences, and Psychiatry. Colleagues at the New York Genome Center and the University of Massachusetts also contributed to the study.

According to Mr. Rajarajan, “There is so much more to the genome than just the four-letter DNA code (A, T, C, G)—such as its folded architecture, which is a highly organized and regulated process. Eighteen years after fully sequencing the human genome, we still understand very little about how it actually comes to life. Our study, and the others that were published, are beginning to unravel more nuances than previously imagined, making it a really exciting time to be in the field of neuroscience and psychiatry research.”

NIMH Program Director Geetha Senthil, PhD, added that the massive scope of the project required a “concerted effort. Many investigators had to come together and do this collectively.” While the mental disorders in the studies are distinct, Dr. Senthil said, “There are some aspects where the biology is similar. The genes interact with each other in a way to influence the disease process. If we can find biological clues early on, we can intervene early on. While we are building and generating more data, analyzing this data to find basic mechanisms, there’s an opportunity also for drug discovery.”

The 10 papers published by the PsychENCODE Consortium were dedicated to the late Pamela Sklar, MD, PhD, former Chair of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine, and a pioneer in genomic brain research, who was an early leader of the NIMH effort. The Icahn School of Medicine last year renamed the division she created the Pamela Sklar Division of Psychiatric Genomics.

Mount Sinai laboratories within The Friedman Brain Institute, The Seaver Autism Center for Research and Treatment, the Department of Psychiatry, The Mindich Child Health and Development Institute, the Department of Genetics and Genomic Sciences, the Department of Neuroscience, and the Icahn Institute for Data Science and Genomic Technology were involved in the PsychENCODE Consortium.

“Mount Sinai serves as one of the lead sites in this national consortium. The discoveries that are being made by our scientists and their colleagues at other major institutions are moving us closer to understanding and finding treatments for these devastating brain disorders,” says Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director of The Friedman Brain Institute, and Dean for Academic and Scientific Affairs, Icahn School of Medicine at Mount Sinai.

Innovations in Psychiatry: New Treatments for Depression

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.

 

APA 2019: Mount Sinai’s Presentations

This year’s American Psychiatric Association (APA) conference takes place May 18-22 in San Francisco. The schedule of sessions presented by faculty from the Department of Psychiatry is listed below.

Veerle Bergink, MD, PhD, will speak on psychiatric illness during and after pregnancy on Tuesday, May 21.

Saturday, May 18

Computers and Psychiatry: How Might Our Practice Change?
Chair: Cheryl Corcoran, MD
When: 8:00-9:30 am
Where: Room 158, Upper Mezzanine, Moscone South

Creating and Implementing a Program for the Mental Health and Wellbeing of Medical Students and Trainees: The Mount Sinai Health System Experience
Chairs: Jeffrey Newcorn, MDPaul Rosenfield, MD
Presenters: Sabina Lim, MD, MPHDaniel Safin, MDJonathan Ripp, MD, MPH
When: 10:00-11:30 am
Where: Room 151, Upper Mezzanine, Moscone South

Sunday, May 19

Sex, Drugs, and Culturally-Responsive Treatment: Addressing Substance Use Disorder in the Context of Sexual and Gender Diversity
Presenter: Faye Chao, MD
When: 8:00-9:30 am
Where: Room 24, Exhibition Level, Moscone North

Advances in the Understanding and Treatment of Treatment Resistant Depression
Chair: James Murrough, MD, PhD
Presenter: Martijn Figee, MD, PhD
When: 8:00-9:30 am
Where: Room 156, Upper Mezzanine, Moscone South

Imminent Suicide Risk Assessment in High-Risk Individuals Denying Suicidal Ideation or Intent
Director: Igor Galynker, MD, PhD
Faculty: Paul Rosenfield, MD
When: 8:00 am-12:00 pm
Where: Room 7, Exhibition Level, Moscone South

The Multiple Faces of Deportation: Being a Solution to the Challenges Faced by Asylum Seekers, Mixed Status Families, and Dreamers
Presenter: Gabrielle Shapiro, MD
When: 10:00-11:30 am
Where: Room 308, Third Level, Moscone South

Disrupting the Cycle of HIV Transmission: The Role of Mental Health Providers in the Inclusive Use of PrEP to Address Disparities
Chair: Kenneth Ashley, MD
When: 3:00-4:30 pm
Where: Rooms 310/311, Third Level, Moscone South

Transitioning from Methadone to Buprenorphine At An Urban Opioid Treatment Program
Chair: Timothy Brennan, MD
Presenters: Annie Levesque, MDPrameet Singh, MD
When: 3:00-4:30 pm
Where: Room 25, Exhibition Level, Moscone North

Monday, May 20

Trauma Inflicted to Immigrant Children and Parents Through Policy of Forced Family Separation
Chair: Gabrielle Shapiro, MD
When: 8:00-9:30 am
Where: Room 303, Third Level, Moscone South

Medical History Mystery Lab
Presenter: Kenneth Ashley, MD
When: 8:00-11:00 am
Where: Room 22, Exhibition Level, Moscone North

A Blueprint for Providing Free, Comprehensive, Integrated Adolescent Health, Transgender Services and Mental Health Care in NYC for $1,000 per Patient
Chair: Kashmira Rustomji, MD
Presenter: John Steever, MD
When: 8:00-9:30 am
Where: Room 314, Third Level, Moscone South

Facing the Challenges of Misuse and Abuse of Stimulant Medications for ADHD: From Neurobiology to Clinical Care
Chair: Jeffrey Newcorn, MD
Presenters: Iliyan Ivanov, MDJeffrey Newcorn, MD
When: 8:00-9:30 am
Where: Room 25, Exhibition Level, Moscone North

Rebels With a Cause: Nurturing the Provider for Successful Program Evolution
Chair: Shilpa Taufique, PhD
Presenter: Brandon Johnson, MD
When: 8:00-9:30 am
Where: Room 206, Second Level, Moscone South

Diagnostic Categories or Dimensions? How Studying the Neural and Genetic Bases of Dimensional Traits Can Help Us Find New Treatments
Chair and presenter: Maria de las Mercedes Perez-Rodriguez, MD, PhD
When: 8:00-9:30 am
Where: Room 213, Second Level, Moscone South

Walking the Walk: Resident Roadmap to Leadership in Psychiatry
Presenter: Adjoa Smalls-Mantey, MD, DPhil
When: 10:00-11:30 am
Where: Room 208, Second Level, Moscone South

No Blacks, Fats, or Femmes: Stereotyping in the Gay Community and Issues of Racism, Body Image, and Masculinity 
Chair: Kenneth Ashley, MD
When: 3:00-4:30 pm
Where: Room 214, Second Level, Moscone South

Training the Next Generation of Community Psychiatrists: Science and Recovery
Chair: Paul Rosenfield, MD
Presenters: Joy Choi, MD;  Tomas Felipe Restrepo Palacio, MD
When: 3:00-4:30 pm
Where: Room 210, Second Level, Moscone South

Tuesday, May 21

Scaling Behavioral Health Integration: One Academic Health Care System’s Approach
Chair: Sabina Lim, MD, MPH
Presenters: Hansel Arroyo, MDKimberly Klipstein, MDRajvee Vora, MD
When: 10:00-11:30 am
Where: Room 314, Third Level, Moscone South

Management of Psychiatric Illness During Pregnancy and Postpartum: What Every Psychiatrist Needs To Know
Chair: Verlee Bergink, MD, PhD
When: 1:00-2:30 pm
Where: Rooms 201/209, Second Level, Moscone South

Typical or Troubled?®: Program Update and Further Development Discussion
Presenter: Gabrielle Shapiro, MD
When: 1:00-2:30 pm
Where: Room 308, Third Level, Moscone South

A Patient-Centered Approach to School Refusal: A Day Program’s Guide to Tackling One of Child and Adolescent Psychiatry’s Most Difficult Problems
Chair: Brandon Johnson, MD
Presenter: Shilpa Taufique, PhD
When: 3:00-4:30 pm
Where: Room 158, Upper Mezzanine, Moscone South

Separating Parents and Children: Impact on Mental Health and Resilience
Chairs: Adriana Feder, MDRachel Yehuda, PhD
When: 3:00-4:30 pm
Where: Room 204, Second Level, Moscone South

From Genetics to Stress Response to Treatment of Personality Disorders
Chair: Maria de las Mercedes Perez-Rodriguez, MD, PhD
When: 3:00-4:30 pm
Where: Room 153, Upper Mezzanine, Moscone South

Wednesday, May 22

New Onset Psychosis: What Trainees, Residents and Early Career Psychiatrists Should Know
Presenters: Cheryl Corcoran, MDIliyan Ivanov, MDDolores Malaspina, MD, MS, MSPHGabrielle Shapiro, MD
When: 8:00-9:30 am
Where: Room 156, Upper Mezzanine, Moscone South

Training Physician-Scientists in Psychiatry: A Road Map to Academic Success
Chairs: Antonia New, MDMaria de las Mercedes Perez-Rodriguez, MD, PhD
Presenters: Kenechi Ejebe, MD, PhDRene Kahn, MD, PhDDrew Kiraly, MD, PhD
When: 3:00-4:30 pm
Where: Room 208, Second Level, Moscone South

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