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 #
3U01MH082022-05S2
Application #
8793697
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
$208,949
Indirect Cost
$40,879
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Velthorst, Eva; Meyer, Eric C; Giuliano, Anthony J et al. (2018) Neurocognitive profiles in the prodrome to psychosis in NAPLS-1. Schizophr Res :
Woods, Scott W; Powers 3rd, Albert R; Taylor, Jerome H et al. (2018) Lack of Diagnostic Pluripotentiality in Patients at Clinical High Risk for Psychosis: Specificity of Comorbidity Persistence and Search for Pluripotential Subgroups. Schizophr Bull 44:254-263
Cao, Hengyi; McEwen, Sarah C; Chung, Yoonho et al. (2018) Altered Brain Activation During Memory Retrieval Precedes and Predicts Conversion to Psychosis in Individuals at Clinical High Risk. Schizophr Bull :
Stowkowy, Jacqueline; Liu, Lu; Cadenhead, Kristin S et al. (2018) Exploration of clinical high-risk dropouts. Schizophr Res 195:579-580
Velthorst, Eva; Zinberg, Jamie; Addington, Jean et al. (2018) Potentially important periods of change in the development of social and role functioning in youth at clinical high risk for psychosis. Dev Psychopathol 30:39-47
Hampton, Joya N; Trotman, Hanan D; Addington, Jean et al. (2018) The relation of atypical antipsychotic use and stress with weight in individuals at clinical high risk for psychosis. Stress Health 34:591-600
Kline, Emily R; Seidman, Larry J; Cornblatt, Barbara A et al. (2018) Depression and clinical high-risk states: Baseline presentation of depressed vs. non-depressed participants in the NAPLS-2 cohort. Schizophr Res 192:357-363
Woodberry, Kristen A; Seidman, Larry J; Bryant, Caitlin et al. (2018) Treatment Precedes Positive Symptoms in North American Adolescent and Young Adult Clinical High Risk Cohort. J Clin Child Adolesc Psychol 47:69-78
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
Lu, Yun; Marshall, Catherine; Cadenhead, Kristin S et al. (2017) Perceptual abnormalities in clinical high risk youth and the role of trauma, cannabis use and anxiety. Psychiatry Res 258:462-468

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