Foundation Joins NIH-Directed Search for Schizophrenia Biomarkers

The APA Foundation is joining the National Institute of Mental Health (NIMH), the National Alliance on Mental Illness (NAMI), and other nonprofit and private organizations, including pharmaceutical companies, in launching a five-year effort to identify early biomarkers of risk for developing schizophrenia.

Part of the Accelerating Medicines Partnership (AMP), AMP Schizophrenia aims to identify promising biological and behavioral 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.

AMP was launched by the National Institutes of Health in February 2014, with projects in three disease areas: Alzheimer’s, type 2 diabetes, and autoimmune disorders of rheumatoid arthritis and systemic lupus erythematosus. In 2018, AMP Parkinson’s disease was added. AMP Schizophrenia is the fifth disease category in the project.

“We know that early intervention in schizophrenia is crucial because it determines the long-term outcome of patients,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A., who is chair of the Board of Directors of the Foundation. “What we have been lacking are reliable biomarkers that can guide targeted interventions. AMP Schizophrenia is a powerful new initiative bringing together the resources and researchers of public and private groups—including our allies at NAMI—to drive new discoveries that might really change treatment of schizophrenia for the better. The Foundation is so pleased to be a part of this effort.”

Chia-Chi Charlie Chang

In comments to Psychiatric News, Joshua Gordon, M.D., Ph.D., director of NIMH, said AMP Schizophrenia represents the first foray of the AMP program into advancing interventions for mental illnesses. “It builds on the success of previous AMP projects, which have proven that a collaborative partnership of industry, nonprofit, and government partners can successfully identify treatment targets across a range of different disease areas,” he said.

Gordon said the project is approaching the identification of novel targets for intervention in stages. “The first stage is to identify biomarkers—including imaging, neurophysiological, cognitive, genetic, and clinical measures—that predict the trajectory of outcomes in the earliest stage of schizophrenia in a very large cohort of individuals who are at clinical high risk [CHR] for psychosis,” he explained. “We hope to integrate the biological and clinical data to develop algorithms that predict progression to psychosis, as well as other adverse outcomes often seen in CHR individuals. The project will then use these algorithms to test the most compelling biological hypotheses using novel pharmacological approaches aimed at improving CHR outcomes.”

He said the first stage of biomarker validation and algorithm development is expected to take place over the first three years of the project. In the second phase of the five-year project, the tools generated in the first phase will be used in proof-of-principle studies to test biological targets for their therapeutic potential.

“With the AMP Schizophrenia program, we seek to understand what is happening in the brains of individuals at clinical high risk for schizophrenia in order to target their specific biology with novel therapies,” Gordon said.

He said 42 participating recruitment sites in the United States, Australia, Europe, and Asia will be recruiting volunteers to participate in CHR Research Networks. Clinicians located in close proximity to one of these sites can help by referring their patients to enroll in the AMP Schizophrenia research study, Gordon said.

All data and analyses will be made publicly available through the NIMH Data Archive.

AMP Schizophrenia complements the NIMH’s Experimental Therapeutics framework, an approach to intervention research begun under former NIMH Director Thomas Insel, M.D. It is designed to use mechanistic hypotheses to guide the development of novel treatments for mental illnesses (see Psychiatric News).

“We hope that AMP Schizophrenia will not only transform treatment and prevention efforts for individuals with schizophrenia, but also provide a paradigm for reinvigorating pharmaceutical company interest in psychiatric drug development more generally,” Gordon told Psychiatric News.

Families Want Better Medications

NAMI Medical Director Kenneth Duckworth, M.D., said that NAMI and its membership have been a driving force behind the need for better therapeutics and the AMP Schizophrenia initiative. “Our members feel strongly that the medications we have for schizophrenia are not sufficient and the process of drug discovery needs to be more innovative,” he told Psychiatric News.

He cited a 2014 editorial in Science by Steven Hyman, M.D., former director of NIMH, lamenting the fact that schizophrenia had been initially turned down as a disease category for the AMP. “Perhaps recent exits by [pharmaceutical] companies from psychiatry made schizophrenia too great a reach for the AMP, despite continued strong support from NIH leadership,” Hyman wrote at the time. “The scientific community, including industry, academia, patient groups, and government, must find ways of sharing financial risk while developing effective and well-governed partnerships.”

Duckworth said the editorial was the impetus for the beginning of a series of meetings—called the Advancing Discovery Summit—that NAMI and the Stanley Research Center began to host. In 2018, Gordon—newly appointed director of NIMH—was a speaker, and that same year a study published in Nature Genetics revealed genes that appear to be significantly associated with risk for schizophrenia.

“AMP Schizophrenia is the flowering of our dream,” he told Psychiatric News.

Duckworth said a patient with schizophrenia will join him as a representative on the AMP Schizophrenia Steering Committee. “You need to have someone with lived experience of this disease,” Duckworth said.

Amy Porfiri, M.B.A., interim director of the APA Foundation, said AMP Schizophrenia is the kind of endeavor that is a perfect fit for the Foundation.

“The Foundation has a long track record of partnering with schools, employers, community-based groups, researchers, and private enterprise to improve services for people with mental illness,” she said. “We look forward to working with NIMH, NAMI, and our partners in the pharmaceutical industry to dramatically improve treatment for people with schizophrenia.” ■