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Yale Researchers to Lead $52M Investigation Into Cause, Effect of Schizophrenia in Some High-risk Adolescents

September 16, 2020

Researchers with the Yale Department of Psychiatry will lead an international investigation to better understand the cause and effect of schizophrenia in some high-risk adolescents and young adults.

The research will be funded by a $52 million grant from the National Institutes of Health and represents one of the largest grants ever awarded to Yale Psychiatry. Scott Woods, MD, Professor of Psychiatry and in the Child Study Center at Yale, is the lead principal investigator along with researchers Carrie E. Bearden from UCLA and John M. Kane from Zucker School of Medicine.

The grant will fund the development of the Psychosis Risk Outcomes Network, or ProNET. The consortium will be based at 27 institutions, where investigators will characterize phenotypes associated with clinical high risk (CHR) or prodrome state of schizophrenia in adolescents and young adults.

CHR has become increasingly recognized as a public health problem that affects the adolescent and young adult population. The development of treatments has been limited by the substantial variation that exists among patients at initial presentation and over time.

Investigators will recruit 1,040 patients with CHR and follow them with clinical and biomarker assessments, including brain structure and function, psychopathology and cognition, genetics, behavior, and natural language and speech, over two years. Two hundred sixty healthy controls will also be assessed at baseline.

In conjunction with a Data Processing, Analysis, and Coordinating Center at Harvard, a network centered in Australia, and the Foundation for the National Institutes of Health’s Accelerating Medicines Partnership for Schizophrenia, ProNET will test whether data-driven variation in these biomarkers can be used to predict individual clinical trajectories and select individual patients most likely to benefit from specific treatments.

“Those of us caring for patients at CHR and working to prevent psychosis have mostly had to make do with treatments that were developed for other disorders and are one-size-fits-all,” Woods said. “ProNET will help prepare the field to develop new treatments that are tailor-made for CHR and for individual patient problem areas.”

Woods is Director of the PRIME Clinic for the Clinical High Risk Syndrome at Yale. He will be assisted by Yale colleagues Alan Anticevic, PhD, Director of the Biomarker Data Transfer Core, and John Cahill, MD, PhD, Director of the Clinical Data Transfer Core. Also assisting will be Al Powers, MD, PhD, who will work with Woods on data collection at the PRIME Clinic site at Yale, and Vinod Srihari, MD, whose investigation will focus on ascertainment issues. Yale Psychiatry Chair John H. Krystal, MD, and Yale Psychology Chair Tyrone Cannon, PhD, are members of the Advisory Board to the PIs.

The grant is a component of NIH’s launch of a new public-private partnership to meet the urgent need for early therapeutic interventions for people at risk of developing schizophrenia. Part of the Accelerating Medicines Partnership (AMP), AMP Schizophrenia brings together NIH, the U.S. Food and Drug Administration and multiple non-profit and private organizations, including Yale.

These partners will work toward the shared mission of discovering promising biological markers that can help identify those at risk of developing schizophrenia as early as possible, track the progression of symptoms and other outcomes and define targets for treatment development.

“We know that with most brain diseases, early interventions before the onset of symptoms improve long-term outcomes,” said NIH Director Francis S. Collins, MD, PhD. “Through research we’ve identified clinical and biological markers for schizophrenia, but we need to translate this knowledge into early interventions to make a meaningful difference in the lives of people at risk for this debilitating disease. AMP Schizophrenia aims to be that bridge.”

This research is supported by the National Institute Of Mental Health of the National Institutes of Health under Award Number U01MH124639. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Submitted by Christopher Gardner on September 14, 2020