Researchers from Harvard Medical School and Massachusetts General Hospital have completed the first phase of a major collaboration to clarify the complex biology underlying neuropsychiatric disorders—an area that has long challenged clinicians and scientists.
The team, led by Isaac Kohane (Harvard Medical School) and Roy Perlis (Massachusetts General Hospital), has established a neuropsychiatric cellular biobank that ranks among the largest of its kind worldwide.
This repository contains induced pluripotent stem cells (iPSCs) generated from skin samples of 100 people diagnosed with neuropsychiatric conditions—including schizophrenia, bipolar disorder, and major depression—and from 50 control participants without neuropsychiatric illness. Each cell line is paired with a detailed clinical profile compiled from hours of in-person assessment and electronic medical records, enabling robust links between molecular features and real-world clinical data.
By providing access to patient-derived cells that reflect the biological diversity of psychiatric conditions, the biobank allows researchers to investigate how cellular and molecular differences map onto clinical outcomes such as symptom patterns, cognitive performance, and variability in medication response. The ultimate aim is to advance precision approaches to diagnosis and treatment in psychiatry, where effective, individualized therapies remain limited.
The cell collection and reprogramming were conducted at Massachusetts General Hospital, while Kohane’s team at Harvard Medical School is leading efforts to comprehensively characterize the lines at a molecular level. The repository—supported by the National Institutes of Health—is housed at Rutgers University and available to qualified investigators.
“This biobank, in its current form, is only the beginning,” said Roy Perlis, director of the MGH Psychiatry Center for Experimental Drugs and Diagnostics and an associate professor of psychiatry at Harvard Medical School. “By next year we’ll have cells from a total of four hundred patients, along with additional clinical detail and new cell types to share with investigators.”
Access to living brain tissue is not feasible for most patients, which has historically restricted the study of psychiatric illness to blood samples or post-mortem brain tissue. In contrast, this iPSC resource offers a means to model neural cells derived from living individuals, creating opportunities to study disease-relevant cell types in the lab and to compare cellular behavior directly with patients’ clinical histories.
A Big Step Forward
Alongside making the cell lines available, researchers at MGH and the Harvard Department of Biomedical Informatics will layer extensive molecular data onto each sample. Planned and ongoing analyses include whole genome sequencing, transcriptomic profiling, and epigenetic assays on neurons and other brain cell types generated from these stem cell lines. These data will help reveal how genetic background and cellular state interact to produce disease-related phenotypes.
Collaborators in Harvard’s Department of Neurobiology, led by Michael Greenberg, will examine additional neuronal subtypes derived from the same stem cell lines to determine whether distinct cell classes show convergent or divergent molecular signatures across diagnoses.
Perlis emphasized the translational potential: “One tangible application would be to compare a patient’s documented treatment response with how their derived neurons respond to medications in vitro. Such correlations could bring precision medicine approaches to psychiatry.”
Isaac Kohane, chair of the Harvard Department of Biomedical Informatics, noted that breakthroughs in genomics required large sample sizes to uncover meaningful disease associations. He added that measuring molecular functioning in patient-derived cells, combined with comprehensive clinical data on treatment response and cognition, may allow important discoveries with fewer patients than required for genetic studies alone.
Perlis also warned against early overinterpretation: “Early genetic studies suffered from false positives due to small sample sizes. We aim to avoid similar pitfalls in cellular modeling by assembling a sufficiently large collection of well-characterized cell lines to detect reliable differences between patient groups.”
Funding: The generation of stem cell lines and the molecular and clinical characterization of patients and brain cell lines are jointly supported by the National Institute of Mental Health, the National Human Genome Research Institute, and a grant from the Centers of Excellence in Genomic Science program.
Source: David Cameron – Harvard Medical School
Image Source: The image is in the public domain