New Research Links Eating Disorders and Obsessive-Compulsive Disorder Through Shared Brain Gene Expression Changes
Largest postmortem brain transcriptomic study of either condition reveals shared biological pathways across two psychiatric conditions with overlapping compulsive behaviors
Researchers at the Icahn School of Medicine at Mount Sinai and the Lieber Institute for Brain Development have identified substantial similarities in brain gene activity among people with eating disorders and obsessive-compulsive disorder (OCD), providing new evidence that the two psychiatric disorders share an underlying biological foundation.
Published June 16 in Cell Reports, the study found that both disorders exhibit highly similar patterns of gene activity in brain circuits involved in habit formation, behavioral control, and decision-making.
The findings offer a biological explanation for the longstanding clinical overlap between eating disorders and OCD, which often share compulsive behaviors, anxiety-related rituals, and responses to similar treatments.
"Clinicians have recognized for decades that eating disorders and OCD frequently overlap, both in symptoms and in treatment response," said Michael S. Breen, PhD, Associate Professor of Psychiatry, and Genetics and Genomic Sciences, at the Icahn School of Medicine at Mount Sinai and first author of the paper. "What had not been tested was whether that overlap extends to the molecular level within the brain. Our findings show that it does."
Using the largest postmortem brain collection assembled for either eating disorders or OCD, the team analyzed gene expression patterns in two cortico-striatal brain regions, the dorsolateral prefrontal cortex and the caudate, from individuals with eating disorders or OCD. These regions govern behavioral flexibility, decision-making, and the development of habitual behaviors.
Across both regions, the investigators found remarkably similar patterns of gene dysregulation in the two disorders. The correlation in gene-level effects between the two disorders was approximately 0.7 in both brain regions, a level of molecular agreement that exceeded expectations for two conditions with distinct clinical presentations and separate diagnostic classifications.
"We expected some degree of overlap, but the magnitude of the similarity was surprising," said Dorothy Grice, MD, Director of the Tics, OCD and Related Disorders Program in the Department of Psychiatry at Mount Sinai. "The same genes were disrupted, in the same directions, across both disorders. That points to shared biological mechanisms underlying compulsive behaviors across diagnostic categories."
The researchers also identified a cluster of five genes on chromosome 3 that emerged independently in both disorders through transcriptome-wide association analyses, highlighting potential molecular targets for future research. Two genes within the region—NCKIPSD and WDR6—emerged as the strongest candidates for future investigation.
In addition, the study identified disruptions within networks regulated by CHD8, a gene previously implicated in OCD and autism spectrum disorder. The findings indicate that CHD8-linked pathways may play a broader role across conditions characterized by compulsive behaviors.
The results point to biological mechanisms that cut across traditional psychiatric diagnoses and may help guide development of treatments that target shared pathways rather than individual disorders.
"Psychiatric drug development has historically focused on one diagnosis at a time," said Dr. Grice. "If multiple disorders share the same molecular disruptions, the same treatment may work across them."
The study's design distinguishes it from previous investigations, which typically focused on a single disorder, a single brain region, or a single patient cohort. By examining two disorders across two brain regions and validating the findings in an independent cohort, the team showed that the observed convergence is a robust biological signal.
The team is now conducting single-nucleus RNA sequencing studies to determine which specific brain cell types drive the molecular changes identified in the current analysis.
"Bulk tissue studies tell us what is disrupted at the population level, but not which cells are responsible," said Dr. Breen. "Our next goal is to identify the specific neuronal populations involved. Ultimately, the goal is to develop treatments guided by biology rather than diagnostic labels."
About the Lieber Institute for Brain Development
The mission of the Lieber Institute for Brain Development and the Maltz Research Laboratories is to translate the understanding of basic genetic and molecular mechanisms of schizophrenia and related developmental brain disorders into clinical advances that change the lives of affected individuals. LIBD is an independent, not-for-profit 501(c)(3) organization and a Maryland tax-exempt medical research institute affiliated with the Johns Hopkins University School of Medicine. The Lieber Institute’s brain repository of nearly 5,000 human brains is the largest collection of postmortem brains for the study of neuropsychiatric disorders worldwide.
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 approximately 48,000 employees working across seven hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and leading schools 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 from conception 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 more than 9,000 primary and specialty care physicians and 10 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’s 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 2025-2026.
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