Groundbreaking maps reveal the complex gene regulation in brains with and without mental disorders, enhancing the understanding of mental illnesses and potential treatments.
A consortium of researchers has produced the largest and most advanced multidimensional maps of gene regulation networks in the brains of people with and without mental disorders. These maps detail the many regulatory elements that coordinate the brain’s biological pathways and cellular functions. The research, supported by the National Institutes of Health (NIH), used postmortem brain tissue from over 2,500 donors to map gene regulation networks across different stages of brain development and multiple brain-related disorders.
“These groundbreaking findings advance our understanding of where, how, and when genetic risk contributes to mental disorders such as schizophrenia, post-traumatic stress disorder, and depression,” said Joshua A. Gordon, M.D., Ph.D., director of NIH’s National Institute of Mental Health (NIMH). “Moreover, the critical resources, shared freely, will help researchers pinpoint genetic variants that are likely to play a causal role in mental illnesses and identify potential molecular targets for new therapeutics.”
The research is published across 15 papers in Science, Science Advances, and Scientific Reports. The papers report findings along several key themes:
- Population-level analyses that link genetic variants, regulatory elements, and different molecular forms of expressed genes to regulatory networks at the cellular level, in both the developing brain and adult brain
- Single-cell-level maps of the prefrontal cortex from individuals diagnosed with mental disorders and neurodevelopmental disorders
- Experimental analyses validating the function of regulatory elements and genetic variants associated with quantitative trait loci (segments of DNA that are linked with observable traits)
The analyses expand on previous findings, exploring multiple cortical and subcortical regions of the human brain. These brain areas play key roles in a range of essential processes, including decision-making, memory, learning, emotion, reward processing, and motor control.
Approximately 2% of the human genome is composed of genes that code for proteins. The remaining 98% includes DNA segments that help regulate the activity of those genes. To better understand how brain structure and function contribute to mental disorders, researchers in the NIMH-funded PsychENCODE Consortium are using standardized methods and data analysis approaches to build a comprehensive picture of these regulatory elements in the human brain.
In addition to these discoveries, the papers also highlight new methods and tools to help researchers analyze and explore the wealth of data produced by this effort. These resources include a web-based platform offering interactive visualization data from diverse brain cell types in individuals with and without mental disorders, known as PsychSCREEN. Together, these methods and tools provide a comprehensive, integrated data resource for the broader research community.
The papers focus on the second phase of findings from the PsychENCODE Consortium. This effort aims to advance our understanding of how gene regulation impacts brain function and dysfunction.
“These PsychENCODE Consortium findings shed new light on how gene risk maps onto brain function across developmental stages, brain regions, and disorders,” said Jonathan Pevsner, Ph.D., chief of the NIMH Genomics Research Branch. “The work lays a strong foundation for ongoing efforts to characterize regulatory pathways across disorders, elucidate the role of epigenetic mechanisms, and increase the ancestral diversity represented in studies.”
The PsychENCODE papers published in Science and Science Advances are presented as a collection on the Science website.
About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.
News
Annual blood test could detect cancer earlier and save lives
A single blood test, designed to pick up chemical signals indicative of the presence of many different types of cancer, could potentially thwart progression to advanced disease while the malignancy is still at an early [...]
How the FDA opens the door to risky chemicals in America’s food supply
Lining the shelves of American supermarkets are food products with chemicals linked to health concerns. To a great extent, the FDA allows food companies to determine for themselves whether their ingredients and additives are [...]
Superbug crisis could get worse, killing nearly 40 million people by 2050
The number of lives lost around the world due to infections that are resistant to the medications intended to treat them could increase nearly 70% by 2050, a new study projects, further showing the [...]
How Can Nanomaterials Be Programmed for Different Applications?
Nanomaterials are no longer just small—they are becoming smart. Across fields like medicine, electronics, energy, and materials science, researchers are now programming nanomaterials to behave in intentional, responsive ways. These advanced materials are designed [...]
Microplastics Are Invading Our Arteries, and It Could Be Increasing Your Risk of Stroke
Higher levels of micronanoplastics were found in carotid artery plaque, especially in people with stroke symptoms, suggesting a potential new risk factor. People with plaque buildup in the arteries of their neck have been [...]
Gene-editing therapy shows early success in fighting advanced gastrointestinal cancers
Researchers at the University of Minnesota have completed a first-in-human clinical trial testing a CRISPR/Cas9 gene-editing technique to help the immune system fight advanced gastrointestinal (GI) cancers. The results, recently published in The Lancet Oncology, show encouraging [...]
Engineered extracellular vesicles facilitate delivery of advanced medicines
Graphic abstract of the development of VEDIC and VFIC systems for high efficiency intracellular protein delivery in vitro and in vivo. Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-59377-y. https://www.nature.com/articles/s41467-025-59377-y Researchers at Karolinska Institutet have developed a technique [...]
Brain-computer interface allows paralyzed users to customize their sense of touch
University of Pittsburgh School of Medicine scientists are one step closer to developing a brain-computer interface, or BCI, that allows people with tetraplegia to restore their lost sense of touch. While exploring a digitally [...]
Scientists Flip a Gut Virus “Kill Switch” – Expose a Hidden Threat in Antibiotic Treatment
Scientists have long known that bacteriophages, viruses that infect bacteria, live in our gut, but exactly what they do has remained elusive. Researchers developed a clever mouse model that can temporarily eliminate these phages [...]
Enhanced Antibacterial Polylactic Acid-Curcumin Nanofibers for Wound Dressing
Background Wound healing is a complex physiological process that can be compromised by infection and impaired tissue regeneration. Conventional dressings, typically made from natural fibers such as cotton or linen, offer limited functionality. Nanofiber [...]
Global Nanomaterial Regulation: A Country-by-Country Comparison
Nanomaterials are materials with at least one dimension smaller than 100 nanometres (about 100,000 times thinner than a human hair). Because of their tiny size, they have unique properties that can be useful in [...]
Pandemic Potential: Scientists Discover 3 Hotspots of Deadly Emerging Disease in the US
Virginia Tech researchers discovered six new rodent carriers of hantavirus and identified U.S. hotspots, highlighting the virus’s adaptability and the impact of climate and ecology on its spread. Hantavirus recently drew public attention following reports [...]
Studies detail high rates of long COVID among healthcare, dental workers
Researchers have estimated approximately 8% of Americas have ever experienced long COVID, or lasting symptoms, following an acute COVID-19 infection. Now two recent international studies suggest that the percentage is much higher among healthcare workers [...]
Melting Arctic Ice May Unleash Ancient Deadly Diseases, Scientists Warn
Melting Arctic ice increases human and animal interactions, raising the risk of infectious disease spread. Researchers urge early intervention and surveillance. Climate change is opening new pathways for the spread of infectious diseases such [...]
Scientists May Have Found a Secret Weapon To Stop Pancreatic Cancer Before It Starts
Researchers at Cold Spring Harbor Laboratory have found that blocking the FGFR2 and EGFR genes can stop early-stage pancreatic cancer from progressing, offering a promising path toward prevention. Pancreatic cancer is expected to become [...]
Breakthrough Drug Restores Vision: Researchers Successfully Reverse Retinal Damage
Blocking the PROX1 protein allowed KAIST researchers to regenerate damaged retinas and restore vision in mice. Vision is one of the most important human senses, yet more than 300 million people around the world are at [...]
