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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/摘要精神分裂症和相关精神病是神经发育障碍，有病理证据变化从子宫内开始；病前神经运动和神经认知异常；疾病前驱期的亚综合征精神病症状（也称为临床高危，CHR）；和青春期后期或成年早期精神病综合征的全面表现。 CHR 研究过去 2 多年，提供了 (i) 对后来转变为完全精神病的风险因素的重要见解 (ii) 开发“精神病风险计算器”，(iii) 与精神病风险相关的生物标志物以及 (iv) 大脑动态变化的证据，这些变化可能在疾病发作前就存在并持续演变分为首发精神病（FEP），以及更慢性的精神病形式。尽管有这些我们对 CHR 状态、长期结果（5 年以上）以及发展轨迹的理解取得了进展很少对这一人群的诊断、症状和心理社会功能进行调查。元- 分析表明，20-30% 的已识别 CHR 个体在 2 年内出现精神病。鲜为人知关于什么类型的精神病（情感性与非情感性）在最初的证据之后“自我宣告” 转化为精神病、后期精神病转化率（即 2-3 年随访期后）或风险可能预测精神病后期发作的因素。大多数符合 CHR 标准的人并不两年内出现明显的精神病，但表现出从完全缓解到持续的症状和功能障碍，至少在相对较短的时间内如此。长期对 CHR 个体的随访提供了一个独特且难得的机会来调查疾病的完整轨迹来自 CHR -> 第一集 -> 慢性疾病，以及有症状个体的长期结果确定后 2 年内未出现精神病。已有大量证据表明 CHR 受试者的多种生物标志物异常。具体来说，CHR 青少年表现出神经认知缺陷，区域皮质灰质、事件相关电位 (ERP) 振幅以及较高的多基因风险评分 (PRS)、炎症标志物和皮质醇相对于比较对象。生物标志物还可以预测谁会 2 年后转变为精神病和功能结果。然而，尚不清楚这些生物标志物是否预测长期转化和结果。具体目标是 1) 长期执行（5-20 年）对多达 2000 名之前符合 CHR 标准的个体进行诊断、症状和功能评估，其中一些人在 9 个学术中心转变为精神病。 2）确定5年以上精神病患者 CHR 个体的转化率以及使用基线人口统计学、临床、功能、神经认知和生物标志物数据可预测转化为个体的长期功能和诊断结果 3) 调查不患有精神病的 CHR 个体的长期诊断和功能结果转化为精神病并测试结果是否受到治疗和药物使用的影响。