Accelerating Science to Advance Early Interventions for Schizophrenia
It unfolds gradually. Grades may start to slip; friendships melt away. You notice new and unusual behaviors, fragmented and circuitous sentences. You wonder what happened to the bright, engaging child you once knew. After a while, you realize—something is really different here. You ask for help and your family doctor sends you to a specialist or an emergency room, and maybe you hear a word you hadn’t really thought of before: schizophrenia.
Schizophrenia is a serious mental illness, affecting multiple facets of the lives of those who bear its burden. Impaired cognition, altered social functioning, and symptoms of psychosis—including disordered thoughts, auditory hallucinations, and paranoid delusions—are all characteristic features of schizophrenia. Untreated, these symptoms can become disabling, impairing one’s ability to learn, work, and participate in family and community life. The good news is that effective treatments are available. A combination of medication, cognitive and behavioral therapies, school and job support, and family education and support can help many, particularly if these interventions are started early in the course of the illness.
Given the importance of early intervention, NIMH-funded research has focused on understanding how schizophrenia emerges in teenagers and young adults. This work has shown that many young people who receive a schizophrenia diagnosis experienced a prolonged period of functional decline before they were diagnosed. Individuals in this clinical high risk (CHR) group face significant challenges. But collectively, this group also offers researchers unique insight into the factors that predict a person’s clinical trajectory. For example, the NIMH-funded North American Prodrome Longitudinal Study has developed a tool that uses clinical and cognitive evaluations to estimate psychosis risk for individuals identified as being at CHR. Getting these folks into treatment programs early may help reduce the impact of the illness and maximize their chances of recovery.
Even with early evidence-based treatment, many individuals with schizophrenia will experience significant, life-altering disability. While modestly effective for psychotic symptoms such as hallucinations or delusions, current pharmacologic treatments often leave the social and cognitive symptoms of schizophrenia untouched. Truly novel advances that transform the lives of those with schizophrenia have proved challenging to discover and develop.
It is now clear that achieving these advances requires a truly novel research effort, one that engages the entire mental health community—scientists, clinicians, pharmaceutical companies, regulators, advocates, and those with lived experience. That is why NIMH, in concert with the Foundation for the National Institutes of Health (FNIH) and public and private partners, just launched the Accelerating Medicines Partnership (AMP) Schizophrenia initiative, part of the broader AMP program managed by FNIH.
AMP Schizophrenia represents the first foray of AMP into research on mental illnesses, and it builds on successful AMP endeavors focused on Alzheimer’s disease, autoimmune disorders, diabetes, and Parkinson’s disease. AMP Schizophrenia partners comprise non-profit organizations, including the American Psychiatric Association Foundation, National Alliance on Mental Illness, One Mind, and Wellcome; pharmaceutical companies, including Boehringer Ingelheim, Janssen, and Otsuka; and federal agencies, including the U.S. Food and Drug Administration, European Medicines Agency, and NIH.
AMP Schizophrenia seeks to capitalize on these partnerships to develop novel treatment approaches that will make a meaningful difference in the lives of individuals identified as being at CHR. It seeks to build on the promise that detection and intervention before psychosis develops could attenuate, postpone, or even prevent the transition to psychosis, and improve individuals’ clinical and functional outcomes. AMP Schizophrenia will develop measures that further define the early stages of risk and predict the likelihood of progression to psychosis and other outcomes. Such tools will enable clinical trials to test new pharmacologic interventions that probe the biological mechanisms leading to the CHR state, aim to treat symptom domains in addition to psychosis, and seek to prevent the onset of schizophrenia.
Getting AMP Schizophrenia off the ground was no easy feat. It has required ongoing support from FNIH, the intense efforts of no fewer than three NIMH Directors (my predecessors, Tom Insel, M.D., and Steve Hyman, M.D., began the process some time ago), a strong push from the National Alliance on Mental Illness, and vigorous engagement from our other partners to bring it to fruition.
The initial effort of AMP Schizophrenia will support a network of academic and community-based research sites to study a large cohort of individuals identified as being at CHR. The lead investigators of this CHR research network include Scott Woods, M.D., at Yale University; Carrie Bearden, Ph.D., at the University of California, Los Angeles; John Kane, M.D., at Northwell Health and Hofstra University; and Barnaby Nelson, Ph.D., and Patrick McGorry, M.D., Ph.D., at Orygen and Melbourne University. Together, these researchers will be recruiting more than 1,000 individuals at CHR across 42 clinical sites, collecting a variety of clinical, behavioral, and biomarker data to understand and predict outcomes.
A data processing, analysis, and coordination center, led by Martha Shenton, Ph.D., at Brigham and Women’s Hospital and Harvard University, and Rene Kahn, M.D., Ph.D., at the Icahn School of Medicine at Mount Sinai, will integrate and analyze CHR biomarker and clinical data generated by the CHR research network and existing CHR-related datasets, in collaboration with the AMP Schizophrenia partners and research network lead investigators. Data from AMP Schizophrenia will be available to the research community for additional analyses via the NIMH Data Archive.
That is just the first phase. In the second phase of the initiative, researchers will use the findings from the CHR cohort to form specific, testable hypotheses about key brain mechanisms underlying the early stages of schizophrenia. The aim is to draw on academic and pharmaceutical industry partners’ expertise to design clinical trials that target these brain mechanisms. With guidance from the nonprofit partners, these trials will also address the specific needs of individuals at CHR, focusing not only on reducing or preventing future illness but also on improving well-being and maximizing recovery in the moment.
We’re very excited about this major step forward. AMP Schizophrenia marks a major public-private partnership for psychiatry—and a major new endeavor aimed squarely at helping reduce the impact of serious mental illnesses. Thanks to all the partners and hard-working people at FNIH and NIMH who helped us get this off the ground, the future looks a little brighter for early intervention in schizophrenia.
Cannon, T. D., Changhong, Y., Addington, J., Bearden, C. E., Cadenhead, K. S., Cornblatt, B. A., Heinssen, R., Jeffries, C. D., Mathalon, D. H., McGlashan, T. H., Perkins, D. O., Seidman, L. J., Tsuang, M. T., Walker, E. F., Woods, S. W., & Kattan, M. W. (2016). An individualized risk calculator for research in prodromal psychosis. The American Journal of Psychiatry, 173(10), 980-988. doi: 10.1176/appi.ajp.2016.15070890