Illuminating key biological pathways that underlie neurodevelopmental and psychiatric disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder, is the goal of a new five-year, $17.9 million grant from the National Institutes of Health's National Institute of Mental Health to a national team of researchers. The research may inform future diagnostic and therapeutic approaches, according to team leader Yongsoo Kim, associate professor of neural and behavioral sciences at the Penn State College of Medicine.
"This is a prestigious recognition of Penn State's excellence in neuroscience research," Kim said. "We're proud to continue advancing critical work in this area."
Neuropsychiatric disorders affect brain development and often emerge in childhood, presenting in diverse ways, which makes treatment difficult. According to the researchers, such disorders affect more than 20% of children and rates are rising. For example, diagnoses of autism spectrum disorder increased 175% between 2011 and 2022.
Recent studies have identified more than 100 genes that affect neurodevelopmental processes and may increase the likelihood of developing neuropsychiatric conditions, Kim said. But it's not clear how these genes, individually or collectively, influence the way the brain develops and functions or how these alterations ultimately give rise to changes in behavior that are linked to clinical symptoms.
"The trouble with neurodevelopment disorders like autism is heterogeneity. They're just so diverse," Kim said. "If we know the brain or cellular phenotype, or the observable traits that are causally related to these conditions, that gives us a biological signature that we can use to diagnose and potentially to develop treatments."
The new award will support the creation of an Assay and Data Generation Center (ADGC) to study 100 different high-risk genes associated with neuropsychiatric conditions in a mouse model. The goal, Kim said, is to understand how they disrupt neurodevelopment and lead to a progression of changes, including in gene expression and cell-level alterations across different cell types in the brain, in brain connectivity and, ultimately, in behavior. The project brings together seven investigators across four institutions - Penn State, New York University (NYU) Langone Health, The Jackson Laboratory and University of Texas (UT) Southwestern Medical Center.
This is one of two grants awarded by the National Institute of Mental Health to expand the Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes (SSPsyGene) Consortium, a national effort to investigate the impact of genes linked to neuropsychiatric and neurodevelopmental disease risk. The consortium's goal is to develop a comprehensive, integrated knowledge base of the associated genes and gene variants and their function that would be available to the biomedical community to advance research on these conditions. The Penn State-led ADGC joins five existing ADGCs in the consortium led by the University of California, Los Angeles; Yale University; Northshore University and Rutgers University; Broad Institute and the Massachusetts Institute of Technology; and Scripps Institute and Broad Institute.
