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

描述/摘要 精神分裂症和相关精神病是神经发育障碍，有病理性证据。 从子宫开始的变化；发病前的神经运动和神经认知异常； 疾病前驱时期的亚综合征精神病症状(也称为临床高危)；以及 青春期晚期或成年期早期精神病综合征的全部表现。对CHR的研究 在过去的20多年里，为后来转变为完全精神病患者提供了(I)对风险因素的重要见解 疾病，(2)开发“精神病风险计算器”，(3)与精神病风险有关的生物标记物和(4) 脑部动态变化的证据，这些变化可能在疾病发生之前就已经存在，并继续演变 转化为首发精神病(FEP)，以及转化为更多的慢性精神病形式。尽管如此 我们对CHR状态、较长期结果(5年以上)以及 在这一人群中，诊断、症状和心理社会功能很少被研究。Meta- 分析表明，20%-30%的已确认的慢性阻塞性肺病患者在两年内发展为精神病。鲜为人知 关于哪种类型的精神病(情感性与非情感性)在最初的 精神病转化率、后来精神病转化率(即2-3年随访期后)或风险 可能预示较晚精神病发作的因素。符合CHR标准的大多数人不符合 在两年内出现明显的精神病，但表现出从完全缓解到 持续的症状和功能损害，至少在这个相对较短的时间范围内。更长期的 对慢性阻塞性肺疾病患者的随访提供了一个独特而难得的机会来研究疾病的整个发展轨迹。 来自慢性疾病的第一集，以及有症状的个人的长期结果 确诊后2年内未发展为精神病的患者。已经有确凿的证据证明 慢性阻塞性肺疾病患者的多项生物标志物异常。具体地说，CHR青年在神经认知方面表现出缺陷， 区域皮质灰质、事件相关电位(ERP)波幅以及较高的多基因风险评分 (Prs)、炎症标志物和皮质醇。生物标记物还可以预测谁会 在两年内转变为精神病和功能结果。然而，目前尚不清楚这些生物标志物是否 预测较长期的转换和结果。具体目标是：1)长期(5-20年) 对多达2000名以前符合CHR标准的人进行诊断、症状和功能评估， 他们中的一些人变成了精神病患者，分布在9个学术中心。2)确定5年以上的精神病患者 CHR个体的转换率和使用基线人口统计、临床、功能、神经认知和 生物标记物数据用于预测转化为 精神病和3)调查慢性阻塞性肺病患者的长期诊断和功能结果。 转换为精神病，并测试结果是否受到治疗和药物使用的影响。

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.