Despite treatment advances, schizophrenia and other psychotic disorders remain seriously disabling, life-long illnesses. As a result, in parallel with other chronic physical illnesses, such as diabetes and heart disease, the scientific focus has begun to shift to early intervention and prevention. In the field of schizophrenia, this focus has generated an interest in the prodromal phase of illness, the stage just prior to florid psychosis. Identification of “prodromal” individuals is based on the presence of subthreshold psychotic symptoms and/or a family history of schizophrenia with signs of functional deterioration. Such “clinical high risk” (CHR) individuals have high rates of conversion to psychosis (ranging from 15-35% in most studies) over about two years. In the early phase of this field, prodromal studies were limited by small sample sizes and lack of attention to biological mechanisms. As a way to overcome these shortcomings, in 2003 we initiated the North American Prodrome Longitudinal Study (NAPLS). Originally, NAPLS was a consortium of eight independent NIMH-funded prodromal studies located at Emory University, Harvard University, University of California Los Angeles (UCLA), University of California San Diego (UCSD), University of North Carolina Chapel Hill, University of Toronto, Yale University, and Zucker Hillside Hospital. The consortium combined previously collected prospective, longitudinal data from these eight sites into a common federated database and produced a series of papers on predictors of psychosis.

In 2008, the NAPLS consortium was awarded a 5-year grant from the National Institute of Mental Health to incorporate biological assessment approaches (neuroimaging, electrophysiological, hormonal and genomics) into a multi-site prospective, longitudinal study of 720 prodromal patients and 240 matched healthy controls. At that time, the University of Calgary replaced the University of Toronto as one of the sites. Among the major advances during this phase of the study (NAPLS 2) was evidence that CHR individuals who converted to psychosis showed a steeper rate of gray matter reduction in prefrontal regions of the brain that appeared to be related to an increase in markers of inflammation.

Most recently, in 2014 NAPLS was competitively renewed for a new 5-year study period (NAPLS 3) to further clarify the roles of neuroinflammation and deficient synaptic plasticity in the development of psychosis, and a ninth site (University of California, San Francisco) was added.