Schizophrenia and other forms of psychosis affect approximately 3% of the population with a disorder that is usually chronic and disabling. The peak age of onset is between ages 18-30, occurring just as life's most productive years are beginning. Although genetic liability and abnormal brain development are known contributing factors, the etiology and pathophysiology of schizophrenia and related syndromes is largely unknown. To date, prospective observation of onset, i.e., the transition from vulnerability to disorder has not been possible because most persons at true risk cannot be identified premorbidly. This has hampered efforts at prevention. However, recent progress in risk ascertainment methodology has enabled reliable identification of help-seeking persons with pre-psychotic or """"""""prodromal"""""""" clinical syndromes who develop psychosis within 1-2 years at rates between 20%-50%. Thus, clinical high-risk populations are now available for tracking prospectively the development and emergence of psychosis. However, because of the low incidence of schizophrenia and the heterogeneity of outcomes in clinical high-risk cases, single site studies cannot efficiently exploit the risk criteria in identifying predictors and mechanisms of psychosis. The NAPLS consortium was created to solve this problem. Eight NIMH-funded sites in North America studying prodromal patients using a common prodromal assessment instrument pooled data to create the largest sample of such persons worldwide (N=291), 35% of whom converted to psychosis after 2 years. An algorithm of baseline data was generated predicting psychosis with about 80% positive predictive power and 40% sensitivity. In this revised proposal, we describe a collaborative prospective study for which we will recruit 800 cases and 400 appropriate controls over 5 years using common, standardized clinical and neurobiological measures.
The aim i s to collect a sample with sufficient size and power to rigorously test elements critical to the liability for and development of psychosis in the biomarker domains of brain structure, electrophysiology, stress hormones, and genomics, and in the clinical domains of prodromal presentation and epidemiology. The revised proposal addresses reviewers'concerns, including the integration of the research plan and measures into a unifying framework. The findings will enhance our ability to identify persons at high risk for imminent psychosis, by refining predictors of conversion, and expanding our understanding of the underlying neural mechanisms. Such knowledge is critical for future efforts at early detection, intervention and prevention of psychotic disorders.
Preventing schizophrenia and other psychoses could relieve an enormous burden of personal and family suffering and economic losses to society. This 8-site project aims to increase our ability to identify high-risk individuals prior to onset and to pinpoint neurobiological changes that underlie the emergence of a psychotic disorder. These efforts are critical to the development of effective preventative intervention strategies for psychotic disorders.
|Addington, Jean; Piskulic, Danijela; Liu, Lu et al. (2017) Comorbid diagnoses for youth at clinical high risk of psychosis. Schizophr Res 190:90-95|
|Chung, Yoonho; Haut, Kristen M; He, George et al. (2017) Ventricular enlargement and progressive reduction of cortical gray matter are linked in prodromal youth who develop psychosis. Schizophr Res 189:169-174|
|Noble, Stephanie; Scheinost, Dustin; Finn, Emily S et al. (2017) Multisite reliability of MR-based functional connectivity. Neuroimage 146:959-970|
|Cannon, Tyrone D; Cao, Hengyi; Mathalon, Daniel H et al. (2017) Reliability of functional magnetic resonance imaging activation during working memory in a multisite study: Clarification and implications for statistical power. Neuroimage 163:456-458|
|Ryan, Arthur T; Addington, Jean; Bearden, Carrie E et al. (2017) Latent class cluster analysis of symptom ratings identifies distinct subgroups within the clinical high risk for psychosis syndrome. Schizophr Res :|
|Stowkowy, Jacqueline; Liu, Lu; Cadenhead, Kristin S et al. (2016) Early traumatic experiences, perceived discrimination and conversion to psychosis in those at clinical high risk for psychosis. Soc Psychiatry Psychiatr Epidemiol 51:497-503|
|McLaughlin, Danielle; Carrión, Ricardo E; Auther, Andrea M et al. (2016) Functional Capacity Assessed by the Map Task in Individuals at Clinical High-Risk for Psychosis. Schizophr Bull 42:1234-42|
|Deighton, Stephanie; Buchy, Lisa; Cadenhead, Kristin S et al. (2016) Traumatic brain injury in individuals at clinical high risk for psychosis. Schizophr Res 174:77-81|
|Moskow, Danielle M; Addington, Jean; Bearden, Carrie E et al. (2016) The relations of age and pubertal development with cortisol and daily stress in youth at clinical risk for psychosis. Schizophr Res 172:29-34|
|Buchy, Lisa; Mathalon, Daniel H; Cannon, Tyrone D et al. (2016) Relation between cannabis use and subcortical volumes in people at clinical high risk of psychosis. Psychiatry Res 254:3-9|
Showing the most recent 10 out of 57 publications