• Press Release

New Study Identifies Genetic Changes in Brain Development That May Contribute to Schizophrenia

Research from Mount Sinai and Harvard Medical School uncovers both inherited and somatic mutations

  • New York, NY
  • (October 10, 2024)

A collaborative study between researchers at the Icahn School of Medicine at Mount Sinai and Harvard Medical School has identified genetic mutations that occur during brain development and may contribute to the development of schizophrenia. This research, published in Science (DOI 10.1126/science.adq1456), reveals that in addition to genes inherited from parents, certain mutations that arise after conception, called somatic mutations, could play a significant role in the disorder's development. 

The study is the first to explore how specific mutations, known as single-nucleotide variants—tiny alterations in a single "letter" of the DNA code—may increase schizophrenia risk alongside inherited genetic factors.  

The researchers studied postmortem brain tissue from individuals with schizophrenia and a group of people without the condition as controls. By sequencing DNA from neurons in the dorsolateral prefrontal cortex, a brain region critical for cognitive function, the team identified single-nucleotide variants. 

This study is significant because it found individuals with schizophrenia had more of these mutations in certain regions of the brain's DNA than those without the condition. Some of these mutations are thought to disrupt important biological processes involved in brain development and function, which could contribute to the symptoms of schizophrenia. 

"This study provides an important insight into the genetic factors contributing to schizophrenia," said co-senior author Andrew Chess, PhD, Professor of Genetics and Genomic Sciences at Icahn Mount Sinai. "Beyond the inherited mutations we typically think of, we now see that mutations arising during brain development may also contribute to the disease." 

Schizophrenia affects around 1 percent of the population globally, making it a significant public health issue. By highlighting the potential role of somatic mutations, this study adds a new layer of complexity to our understanding of the disease. It also underscores the importance of investigating both inherited and non-inherited genetic changes to fully comprehend how schizophrenia develops. 

The researchers also found that some of the mutations had a molecular signature previously seen in mutations arising after inflammation, consistent with the possibility that environmental factors, such as maternal infection during pregnancy, may play a role in the development of schizophrenia. These findings could inform future therapeutic approaches by identifying new genetic targets for drug development. 

This study marks a pioneering effort in exploring the role of single-nucleotide variants in schizophrenia. The authors plan to expand their research by analyzing a larger number of individuals and leveraging emerging DNA technologies to examine the genes affected by these somatic mutations in greater detail. The ultimate goal is to deepen our understanding of how these genetic changes impact brain development and contribute to mental health disorders. 

"As we continue to explore these mutations and their effects on brain function, we hope to uncover new pathways for potential therapeutic interventions," Dr. Chess added. "By expanding the number of cases we study and using cutting-edge technologies, we aim to better understand the genetic mechanisms behind schizophrenia and ultimately improve outcomes for those affected by the disorder."

The paper is titled “Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes.”

This research is supported by National Institutes of Health grant numbers K01AG051791, DP2AG072437, R35GM127131, R01MH101244, U01HG012009, R00HG010669, R01HG012872, R56MH12784, R01MH106056, R01MH123155, and R01MH125579 and National Institute of Mental Health U01MH10681, U01MH106876, and U01MH106883. 

  

About the Icahn School of Medicine at Mount Sinai 

The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight- member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population.   

Ranked 13th nationwide in National Institutes of Health (NIH) funding and among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators, and clinicians work within and across 44 academic departments and 36 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, as well as gastrointestinal and liver diseases.  

Icahn Mount Sinai offers highly competitive MD, PhD, and Master’s degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,000 clinical residents and fellows training throughout the Health System. In addition, more than 550 postdoctoral research fellows are in training within the Health System.  

A culture of innovation and discovery permeates every Icahn Mount Sinai program. Mount Sinai’s technology transfer office, one of the largest in the country, partners with faculty and trainees to pursue optimal commercialization of intellectual property to ensure that Mount Sinai discoveries and innovations translate into healthcare products and services that benefit the public.  

Icahn Mount Sinai’s commitment to breakthrough science and clinical care is enhanced by academic affiliations that supplement and complement the School’s programs.  

Through the Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai. Additionally, MSIP develops research partnerships with industry leaders such as Merck & Co., AstraZeneca, Novo Nordisk, and others.  

The Icahn School of Medicine at Mount Sinai is located in New York City on the border between the Upper East Side and East Harlem, and classroom teaching takes place on a campus facing Central Park. Icahn Mount Sinai’s location offers many opportunities to interact with and care for diverse communities. Learning extends well beyond the borders of our physical campus, to the eight hospitals of the Mount Sinai Health System, our academic affiliates, and globally.  

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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Beth Israel; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.  


About the Mount Sinai Health System

Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.

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