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Predictors and Moderators of Long-Term Outcome of Persons at Clinical High Risk for Psychosis

精神病临床高危人群长期结果的预测因素和调节因素

基本信息

批准号：
10642937
负责人：
KRISTIN S. CADENHEAD
金额：
$ 107.35万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-05 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10642937
关键词：
Adolescence Affective Affective Symptoms Age Anxiety Biological Markers Brain Characteristics Chronic Chronic Disease Clinical Data Development Diagnosis Diagnostic Disease Disease remission EP300 gene Event-Related Potentials Female Future Gender Hydrocortisone Impairment Individual Link Meta-Analysis Modeling Moods Neurocognition Neurocognitive Neurocognitive Deficit Neurodevelopmental Disorder Onset of illness Outcome Parents Participant Pathologic Persons Phase Population Population Heterogeneity Psychoses Psychotic Disorders Research Retrospective Studies Risk Factors Role Schizophrenia Symptoms Syndrome Testing Time Trauma Youth clinical high risk for psychosis comorbidity design diagnostic criteria duration of untreated psychosis emerging adult first episode psychosis follow-up functional disability functional outcomes gray matter high risk high risk population improved in utero inflammatory marker insight meetings non-affective psychoses outcome prediction polygenic risk score predictive marker prospective psychosis risk psychosocial psychotic psychotic symptoms social substance use white matter

项目摘要

Description/Abstract Schizophrenia and related psychotic illnesses are neurodevelopmental disorders with evidence of pathological changes beginning in utero; neuromotor and neurocognitive abnormalities in the premorbid period; subsyndromal psychotic symptoms in the prodromal period of illness (also called clinical high risk, CHR); and full manifestation of a psychotic syndrome during late adolescence or early adulthood. CHR research over the past 2+ decades, has provided (i) important insights into risk factors for later conversion to full psychotic illness, (ii) the development of a “Psychosis Risk Calculator”, (iii) biomarkers linked to psychosis riskand (iv) evidence of dynamic brain changes that are likely present before the onset of illness and continue to evolve into the first episode psychosis (FEP), as well as into more chronic forms of psychosis. Despite these advances in our understanding of the CHR state, the longer-term outcomes (5+ years), and the trajectory of diagnoses, symptoms and psychosocial function have been seldom investigated in this population. Meta- analyses show that 20-30% of identified CHR individuals develop psychosis within 2 years. Little is known about what type of psychosis (affective versus non-affective) "declares itself" after evidence of the initial conversion to psychosis, the rate of later psychotic conversion (i.e. post 2-3-year follow-up periods) or risk factors that might predict a later onset of psychosis. The majority of individuals who meet CHR criteria do not develop overt psychosis within 2 years but demonstrate outcomes ranging from complete remission to continued symptoms and functional impairment, at least within this relatively short time frame. Longer-term follow-up of CHR individuals provides a unique and rare opportunity to investigate the full trajectory of illness from CHR -> First Episode -> Chronic Illness, in addition to longer-term outcomes in symptomatic individuals who did not develop psychosis within 2 years after ascertainment. Substantial evidence already exists for multiple biomarker abnormalities in CHR subjects. Specifically, CHR youth show deficits in neurocognition, regional cortical gray matter, event related potential (ERP) amplitudes as well as higher polygenic risk scores (PRS), inflammatory markers and cortisol relative to comparison subjects. Biomarkers also predict who will convert to psychosis and functional outcomes at 2 years. However, it is not known whether these biomarkers predict longer term conversion and outcomes. The Specific Aims are to 1) Perform long-term (5-20 year) diagnostic, symptom and functional assessments of up to 2000 individuals who previously met CHR criteria, some of whom converted to psychosis, across 9 academic centers. 2) Determine the 5+ year psychotic conversion rate of CHR individuals and use baseline demographic, clinical, functional, neurocognitive and biomarker data to predict longer term functional and diagnostic outcomes of individuals who convert to psychosis and 3) Investigate the long-term diagnostic and functional outcomes of CHR individuals who do not convert to psychosis and test whether outcomes are influenced by treatment and substance use.

描述/文摘