New Research Seeks to Decode Genetic Basis of Mental Illness

Neurodevelopmental and psychiatric disorders (NPD), including schizophrenia, bipolar disorder, autism, and depression, significantly impact individuals, families, and society. Despite their profound effects, effective treatments remain scarce. A growing body of evidence suggests that genetic mutations in specific genes can increase the risk of developing these disorders. To date, hundreds of these "risk genes" have been identified, but their precise role in NPD remains largely unclear.

David Panchision, Chief of the Developmental and Genomic Neuroscience Research Branch at the National Institute of Mental Health (NIMH), emphasizes the challenge: “Very little is known about the basic function of most of these genes, and what we do know often comes from research in cancer cell lines rather than brain cell types.” This gap in knowledge has left researchers without a clear understanding of how changes in these genes may individually or collectively contribute to neurodevelopmental and psychiatric disorders.

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In response to this challenge, the NIMH launched a groundbreaking initiative in 2023 known as SSPsyGene. This consortium, which can be explored at brings together research teams from several prestigious U.S. universities with a unified objective: to characterize the genetic foundations of NPD by focusing on 250 high-risk genes.

Notable contributors to this effort include Jubao Duan from Endeavor Health (formerly NorthShore University Health System) and the University of Chicago, and Zhiping Pang from Rutgers University. Their teams have developed a novel method for systematically mutating NPD risk genes in human stem cells. By introducing mutations that disrupt the production of functional proteins, researchers can create modified stem cells that are then differentiated into neurons and other brain cells. This process allows for the modeling of how mutations in risk genes impact brain function in a controlled, laboratory-based setting.

In the initial phase of this project, researchers focused on 23 specific NPD risk genes. Their findings include the creation of stem cell lines that will be shared with the global research community. This open access to modified stem cells is expected to accelerate studies into these risk genes and their role in NPD.

Looking ahead, Pang, Duan, and their consortium partners plan to expand their efforts to include a broader array of risk genes. The ultimate goal is to enhance the understanding of genetic causes of neurodevelopmental and psychiatric disorders, paving the way for more effective treatments.