Updated on Jun 30, 2022 | Featured, Research
From left: Scott Russo, PhD, with researchers Hossein Aleyasin, MD, PhD, and Caroline Menard, PhD, postdoctoral fellows in the Department of Neuroscience.
A team of researchers at the Icahn School of Medicine at Mount Sinai has conducted a pioneering study of mice behavior and the structure of the brain demonstrating that in some cases, aggressive social interaction— bullying—activates a primary brain reward circuit that makes the activity pleasurable.
The study, led by Scott Russo, PhD, Associate Professor of Neuroscience, appeared in the journal Nature in 2016. Significantly, it was the first time that researchers discovered that specific neural mechanisms between the basal forebrain and lateral habenula mediate the motivation to engage in or avoid this aggressive behavior. Furthermore, they showed that manipulating activity in this circuit alters the activity of brain cells and, ultimately, aggression behavior.
The team used a conventional mouse behavioral model whereby adult mice were placed together with a younger subordinate mouse for three minutes each day for three consecutive days while researchers closely watched their behavior. They determined that with specific conditioning, about 70 percent of mice exhibited aggressive behavior, tending to bully or attack the subordinate mouse, while 30 percent showed no aggression at all. They also observed behavior suggesting that the aggressive mice found the ability to subordinate others rewarding, while the non-aggressive mice developed an aversion to aggression stimuli.
By studying brain activity, the researchers found that the aggressive mice, when given the chance to bully, exhibited increased activity in the basal forebrain neurons that reduce activity in the lateral habenula, an area of the brain that would normally encode an aversion to aggressive stimuli. Conversely, they found that non-aggressive mice exhibited reduced basal forebrain activation and a subsequent increase in lateral habenula neuronal firing, which makes the aggression stimuli aversive.
A scan of tissue from a mouse brain shows an inhibitory neuron (green) in the basal forebrain, which projects directly to the lateral habenula, a circuit that controls aggression.
Researchers then directly manipulated the activity of the neurotransmitter that has a role in this circuit. “When we artificially induced the rapid neuron activation between the basal forebrain and lateral habenula, we watched in real time as the aggressive mice became docile and no longer showed bullying behavior—it was very dramatic,” says Dr. Russo. “Our study is unique in that we took information about the basal forebrain-lateral habenula projections and then actually went back and manipulated these connections within animals to conclusively show that the circuits bi-directionally control aggression behavior.”
Over the years, Dr. Russo says there have been only limited studies on aggression, even though aggression can be a major part of human illness. This research, while promising, is still in its early stages. “It could take 10 years before we have anything ready for testing in humans, but this is a critical first step,” Dr. Russo says. “Targeting shared underlying deficits in motivational circuitry may eventually provide useful information for the development of novel therapeutic drugs for treating aggression-related neuropsychiatric disorders.”
The Mount Sinai research team included investigators from the Fishberg Department of Neuroscience, The Friedman Brain Institute, the Graduate Program in Neuroscience, the Department of Pharmacological Sciences, and the Mount Sinai Institute for Systems Biomedicine.
Updated on Jun 30, 2022 | Community, Featured, Research
Prabhjot Singh, MD, PhD, Director of The Arnhold Institute for Global Health, right, with, from left: Hilda Mejias, a Health Coach in Harlem, and Anna Stapleton, Program Manager for Policy at The Arnhold Institute for Global Health.
The United States spends more money on health care than any other country, yet has poorer outcomes with shorter average life expectancies (78.8 years, per capita) than peer nations, such as Japan and Spain, with 83.4 years and 83.2 years, respectively. Furthermore, a child born in poverty in Detroit has a life expectancy that is six years shorter than a child born in similar circumstances in New York City. And someone born on the Upper East Side of Manhattan has a life expectancy that is nine years longer than a person born ten blocks away in East Harlem.
Mending this uneven patchwork of U.S. health outcomes will require a new model of care that embraces the use of community health workers (CHWs), non-clinical workers who provide underserved patients with the continuum of care they need, according to a new report from The Arnhold Institute for Global Health at the Icahn School of Medicine at Mount Sinai and the Office of the UN Secretary General’s Special Envoy for Health in Agenda 2030 and for Malaria. The report recommends creating a pilot program in Newark, New Jersey, a city with many non-English speaking residents that lags behind the rest of the state in health outcomes.
CHWs come from the same communities as their patients and serve as the primary mechanism that enables patients to live healthier lives. They can serve as educators, for example, explaining the relationship between diabetes, blood sugar, high-sugar foods, and insulin in a way patients understand, or link patients to neighborhood exercise groups or food pantries that provide health-conscious meals. Such programs have been successful in South America, sub-Saharan Africa, and Southeast Asia.
“A growing body of evidence tells us that social, economic, genomic, and cultural factors can impact an individual’s ability to build and maintain health, and community health workers have the ability to help bridge that gap between medical advice and a patient’s ability to comply,” says Prabhjot Singh, MD, PhD, Director of The Arnhold Institute for Global Health, and the report’s senior author. Dr. Singh co-founded the One Million Community Health Worker Campaign with Jeffrey Sachs, an author and well-regarded sustainable development leader, whom The Arnhold Institute for Global Health is hosting as a visiting fellow through 2018.
Claire Qureshi, MBA, Vice President of Frontline Delivery, Office of the UN Special Envoy for Health in Agenda 2030 and for Malaria, co-wrote the report with Dr. Singh. “We’ve seen the health impact and economic value of CHWs in countries around the world and fundamentally believe that working with them as part of integrated primary care is a better way to practice medicine,” says Ms. Qureshi. “With careful construction of the right care models, including the organizational and financial infrastructure needed to support them, CHWs can contribute enormously to patients, communities, and health systems alike.”
While CHWs have existed in the United States for decades, they have struggled to gain widespread acceptance. The services they provide have not been reimbursed by public or private health insurance plans, which are based on traditional fee-for-service payments made to hospitals and clinics. In this old model of health care, there has been little incentive to pay for the preventive and maintenance support provided by CHWs, and little consideration given to the support patients need to comply with the medical advice they receive.
But that is changing. The country’s new emphasis on keeping populations healthy and out of the hospital is creating fertile ground for robust, sustainable CHW programs to emerge, according to the report.
Updated on Jun 30, 2022 | Featured, Research
The Icahn School of Medicine at Mount Sinai will receive $4.7 million from the National Institutes of Health (NIH) to participate in a landmark study with 20 other research centers that will examine how childhood experiences and habits affect brain development and, ultimately, social, behavioral, academic, and health outcomes.
The NIH initiative, known as the Adolescent Brain Cognitive Development (ABCD) study, will follow approximately 10,000 children for 10 years, beginning at ages 9 and 10, through adolescence, and into early adulthood. Researchers will use advanced brain imaging, interviews, and behavioral testing to determine how video games, school sports, sleep habits, social media, smoking, alcohol, and drug use interact with each other and with a child’s changing biology to alter the development of the brain over the short and long terms.
Rita Goldstein, PhD, Professor of Psychiatry, and Neuroscience, and Chief of the Neuropsychoimaging of Addiction and Related Conditions research group and the Brain Imaging Core at the Icahn School of Medicine, is Mount Sinai’s principal investigator on the study. Dr. Goldstein and her team will collaborate with Yale University to recruit more than 1,000 children, an effort that will unfold over the next two years through partnerships with public and private schools.
The ABCD study is “a paradigm shift for the brain development study,” says Dr. Goldstein. “Multimodal neuroimaging studies to uncover brain mechanisms that could change over time with development and shed light on health, resilience, and vulnerability factors have not been conducted at this scale before, making this project both exciting and crucially important.”
An additional partnership with BJ Casey, PhD, the study’s principal investigator at Yale, will enable Dr. Goldstein’s team to study the cortical-subcortical pathways that underlie select behaviors crucial during the adolescent years.
“Such early identification of the dynamics of brain states, pathways, and mechanisms is crucial for enhancing the understanding of factors that may contribute to certain behaviors,” says Dr. Goldstein. “We will also be able to identify the brain circuits and pathways that may predispose to or protect against certain risks. The identification of mechanisms underlying resilience has always been an important focus at Mount Sinai.”
Ultimately, the study is expected to provide parents, school principals and teachers, medical professionals, and public policymakers with useful data to promote the health, well-being, and success of children.
“We know the brain is still developing well into the mid-20s, making it vulnerable to a host of influences,” said NIH Director Francis S. Collins, MD, PhD, in announcing the initiative. “With several NIH institutes and centers working together on this important study, we will be able to learn how a variety of biological events and environmental exposures affect brain development, giving us greater insight into what helps adolescents traverse that potentially tumultuous time to become healthy and productive adults.”
For additional information, please call 844-422-2301, email: abcd@mssm.edu, or visit our web sign-up page: http://tinyurl.com/mssm-ABCD.
Updated on Jun 30, 2022 | Featured, Research
Aaron E. Miller, MD, left, and Fred D. Lublin, MD, helped lead groundbreaking multiple sclerosis research.
Three multicenter Phase III trials in which Mount Sinai researchers played key roles have reported highly encouraging results for the investigational drug ocrelizumab in treating both primary progressive multiple sclerosis (MS), the most disabling form of the disease, as well as relapsing MS, the most prevalent form. Two of the three trials, known as OPERA I and OPERA II, were focused on relapsing MS. The third trial, ORATORIO, was aimed at primary progressive MS. The findings were published online Wednesday, December 21, 2016, in The New England Journal of Medicine (NEJM). “The results for ORATORIO were truly groundbreaking because we never before had a treatment that was proven to work with primary progressive MS,” says Aaron E. Miller, MD, Professor of Neurology at the Icahn School of Medicine at Mount Sinai and Medical Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai. “In the case of relapsing MS, we have had many options in the past, but this new treatment has extremely good efficacy and will probably be widely used for patients with the disease.”
MS is a complicated, often disabling, disease of the central nervous system that can produce a wide variety of neurological symptoms as it disrupts the flow of information within the brain and spinal cord, and between the brain and body. It afflicts an estimated 2.3 million people worldwide and 400,000 in the United States. Approximately 10 to 15 percent of this population is diagnosed with primary progressive MS, in which patients, instead of relapsing and recovering partly or fully, experience gradual deterioration from disease onset.
According to Dr. Miller, who served as principal investigator at Mount Sinai for ORATORIO, ocrelizumab significantly reduced the progression of clinical disability of primary progressive MS at both 12 and 24 weeks—a finding that prompted the NEJM to hail the trial in an editorial as a “landmark study in the field.”
Fred D. Lublin, MD, Saunders Family Professor of Neurology at the Icahn School of Medicine at Mount Sinai and Director of the Corinne Goldsmith Dickinson Center, was a member of the steering committee that designed and monitored ORATORIO. Dr. Lublin was also an author for OPERA I and OPERA II, which found that ocrelizumab resulted in 46 to 47 percent lower relapse rates than interferon beta-1a, a current leading treatment for relapsing MS. Ocrelizumab, from Genentech, a member of the Roche Group, was created to treat both forms of the disease. A humanized monoclonal antibody, ocrelizumab binds to CD-20 proteins on the surface of certain B cells, causing their depletion. B cells are believed to be a key contributor to attacks on the insulation and support around nerve fibers in the brain, spinal cord, and optic nerves that can lead to disability. Ocrelizumab is administered by intravenous infusion every six months.
“Every study brings us closer to a cure, and now we have opened the door to a whole new group: patients with primary progressive MS, whom we can more successfully treat,” Dr. Lublin says. “The next challenge is to see if we can select patients most likely to respond to this therapy.”
Updated on Jun 30, 2022 | Patient Stories, Research
Emma Guttman-Yassky, MD, PhD, Professor of Dermatology and Vice Chair of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai, is involved in a clinical trial for a potential new treatment for atopic dermatitis.
Updated on Jun 30, 2022 | Research
Fred Lublin, MD, director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis
As many as 400,000 Americans are believed to suffer from multiple sclerosis — a debilitating disease of the central nervous system. A new drug may provide relief from the most devastating form of MS. Fred Lublin, MD, director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at The Mount Sinai Hospital, worked on the trial.
