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

• 批准号: 10207198
• 负责人: KRISTIN S. CADENHEAD
• 金额: $ 121.46万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 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/10207198
• 关键词: Adolescence; Affective; Affective Symptoms; Age; Anxiety; Archives; Biological Markers; Brain; Characteristics; Chronic; Chronic Disease; Clinical; Data; Development; Diagnosis; Diagnostic; Disease; Disease remission; Event-Related Potentials; Female; Future; Gender; Hydrocortisone; Impairment; Individual; Inflammatory; 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; Risk Factors; Role; Schizophrenia; Symptoms; Syndrome; Testing; Time; Trauma; Youth; base; comorbidity; design; emerging adult; first episode psychosis; follow-up; functional disability; functional outcomes; gray matter; high risk; high risk population; in utero; inflammatory marker; insight; meetings; outcome prediction; polygenic risk score; predictive marker; prospective; psychosocial; psychotic symptoms; substance use; white matter

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 精神分裂症和相关的精神病是神经发育障碍，有病理的证据 变化从子宫开始；在病前期的神经运动和神经认知异常； 在疾病的前驱时期（也称为临床高风险，CHR）；和 在青少年后期或成年初期的精神病综合征的完全表现。 CHR研究 过去20多年，（i）对以后转换为完全精神病的风险因素的重要见解 疾病，（ii）开发“精神病风险计算器”，（iii）与精神病风险和IV相关的生物标志物（IV） 疾病发作之前可能存在动态大脑变化的证据并继续进化 进入第一集精神病（FEP），以及更慢性的精神病。尽管如此 我们对CHR状态的理解，长期结局（5年以上）和轨迹的进步 在该人群中很少研究诊断，符号和社会心理功能。元 - 分析表明，有20-30％的CHR患者在2年内发展精神病。鲜为人知 关于哪种类型的精神病（情感与非影响力）“声明自己” 转换为精神病，后来的精神病转换率（即2 - 3年后随访期）或风险 可能预测精神病的后期发作的因素。符合CHR标准的大多数人都不 在2年内发展出明显的精神病，但展示了从完全缓解到的结果 持续的符号和功能障碍至少在相对较短的时间范围内。长期 CHR个人的随访提供了一个独特而难得的机会来调查疾病的全部轨迹 从chr->第一集 - >慢性疾病，除了有症状的个体的长期结局 在确定后的2年内没有发展精神病。已经存在大量证据 CHR受试者中多种生物标志物异常。具体而言，CHR青年在神经认知方面的定义， 区域皮质灰质，事件相关电位（ERP）放大器以及更高的多基因风险评分 （PR），相对于比较受试者，炎症标记和皮质醇。生物标志物还预测谁将 转化为2年的精神病和功能结果。但是，尚不知道这些生物标志物是否 预测长期转换和结果。具体目的是1）长期执行（5 - 20年） 多达2000名以前符合CHR标准的人的诊断，症状和功能评估， 其中一些人跨9个学术中心转变为精神病。 2）确定5年以上的精神病 CHR个体的转化率并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换为的个人的长期功能和诊断结果 精神病和3）调查没有 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。