New Clinical Insights and Unfolding Genetic and Neurobiological Knowledge Hold Promise for Schizophrenia

New Clinical Insights and Unfolding Genetic and Neurobiological Knowledge Hold Promise for Schizophrenia

THE NEUROSCIENCE COMMUNITY at Mount Sinai continues to grow and flourish. Over the past year, we have welcomed more than 10 new research faculty to The Friedman Brain Institute’s constituent departments, with several more expected to join us in the coming months.

Our departments of Neuroscience and Psychiatry are Top 10 in the nation for National Institutes of Health funding, while Neurology and Rehabilitation Medicine are in the Top 20, with Neurosurgery very close behind.

Additionally, Neurology & Neurosurgery are currently ranked No. 9 in the nation by U.S. News & World Report, and Psychiatry is ranked in the Top 20. This spectacular growth and recognition is powered greatly by philanthropy, making ours one of the strongest institutes for brain research, education, and clinical care in the world.

  • Top 10 in the Nation for NIH Funding in Neuroscience and Psychiatry

This Fall 2022 issue of the Friedman Brain Institute (FBI) newsletter focuses on one such area of investment: schizophrenia. Schizophrenia and related psychotic disorders are among the top 10 causes of disability worldwide, yet the diagnosis and treatment of these illnesses have changed little since I was a resident in psychiatry more than three decades ago.

  • We are encouraged by recent advances…

  • ...and believe, for the first time, there is good reason for optimism.

The absence of pathognomonic (diagnostic) anatomical abnormalities to define schizophrenia, the lack of access to the brains of people with schizophrenia, and the inability to access core symptoms of the illness (for example, hallucinations, delusions, abnormal thinking) in animal or cell models have long stymied progress in the field. Yet, we are encouraged by recent advances—which we highlight in this newsletter—and believe that, for the first time, there is good reason for optimism.

Schizophrenia is highly heritable and tremendous progress is being made in identifying the genomic variations that comprise that risk. The knowledge that variations in many hundreds of genomic regions are involved raises new challenges that scientists are now working to overcome. In parallel, advances in neuroscience are enabling us to relate genomic risk to associated abnormalities in gene expression and chromatin structure (for example, epigenetics) and, in turn, to relate these molecular features to the functioning of individual nerve cells and the complex circuits in which they operate. Today, it is possible to understand such molecular, cellular, circuit, and behavioral domains across species—from rodents to nonhuman primates, to humans, and back to animal models—at unprecedented levels.

At the same time, advances in artificial intelligence and machine learning are likewise making the vast amounts of clinical information available in patients’ electronic health records accessible to scientists, allowing them to gain new insight into the course of illness and open a window into the extraordinary heterogeneity that characterizes psychotic- spectrum syndromes.

By combining this new clinical insight with evolving genetic and neurobiological knowledge, it is our expectation that at long last our work will yield improved diagnostic tests, more effective treatments, and specific preventive measures for these devastating conditions.

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Eric J. Nestler, MD, PhD

Eric J. Nestler, MD, PhD

Nash Family Professor of Neuroscience, Director, The Friedman Brain Institute, Dean for Academic Affairs, Icahn School of Medicine at Mount Sinai; Chief Scientific Officer, Mount Sinai Health System