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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01MH081928-05S2
Application #
8793665
Study Section
Special Emphasis Panel (ZRG1-BBBP-D (60))
Program Officer
Rumsey, Judith M
Project Start
2008-09-30
Project End
2014-09-30
Budget Start
2014-02-01
Budget End
2014-09-30
Support Year
5
Fiscal Year
2014
Total Cost
$184,132
Indirect Cost
$78,309
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Forsyth, Jennifer K; McEwen, Sarah C; Gee, Dylan G et al. (2014) Reliability of functional magnetic resonance imaging activation during working memory in a multi-site study: analysis from the North American Prodrome Longitudinal Study. Neuroimage 97:41-52
Woodberry, Kristen A; Serur, Rachael A; Hallinan, Sean B et al. (2014) Frequency and pattern of childhood symptom onset reported by first episode schizophrenia and clinical high risk youth. Schizophr Res 158:45-51
Meyer, Eric C; CarriĆ³n, Ricardo E; Cornblatt, Barbara A et al. (2014) The relationship of neurocognition and negative symptoms to social and role functioning over time in individuals at clinical high risk in the first phase of the North American Prodrome Longitudinal Study. Schizophr Bull 40:1452-61
Del Re, E C; Bergen, S E; Mesholam-Gately, R I et al. (2014) Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds. Transl Psychiatry 4:e346
Marshall, Catherine; Denny, Erin; Cadenhead, Kristin S et al. (2014) The content of attenuated psychotic symptoms in those at clinical high risk for psychosis. Psychiatry Res 219:506-12
Saleem, Majid M; Stowkowy, Jacqueline; Cadenhead, Kristin S et al. (2014) Perceived discrimination in those at clinical high risk for psychosis. Early Interv Psychiatry 8:77-81
Woods, Scott W; Walsh, Barbara C; Addington, Jean et al. (2014) Current status specifiers for patients at clinical high risk for psychosis. Schizophr Res 158:69-75
Li, Huijun; Friedman-Yakoobian, Michelle; Min, Grace et al. (2013) Working with Asian American youth at clinical high risk for psychosis: a case illustration. J Nerv Ment Dis 201:484-9
Walder, Deborah J; Holtzman, Carrie W; Addington, Jean et al. (2013) Sexual dimorphisms and prediction of conversion in the NAPLS psychosis prodrome. Schizophr Res 144:43-50
Woods, Scott W; Addington, Jean; Bearden, Carrie E et al. (2013) Psychotropic medication use in youth at high risk for psychosis: comparison of baseline data from two research cohorts 1998-2005 and 2008-2011. Schizophr Res 148:99-104

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