Cognitive-Affective Psychosis Proneness Risk and protective factors in 22q11.2DS

22q11.2DS 认知情感精神病倾向的风险和保护因素

• 批准号: 9317531
• 负责人: TONY J SIMON
• 金额: $ 64.3万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9317531
• 关键词: 18 year old; 22q; 22q11; 22q11.2; Adolescence; Adolescent and Young Adult; Affect; Affective; Age; Age-Years; Anxiety; Attention; Attenuated; Biological Assay; Biological Markers; Brain; Categories; Chromosomes; Chronic stress; Clinical; Cognition; Cognitive; Cognitive deficits; Complement; Complex; Data; Development; Dimensions; Disease; Early identification; Emotional; Event-Related Potentials; Exhibits; Factor Analysis; Fright; Functional Imaging; Genetic; Genetic Predisposition to Disease; Genetic Risk; Gold; Grant; Hormones; Hydrocortisone; Impaired cognition; Impairment; Individual; Lead; Life; Link; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Mental Health; Modeling; Nature; Neurobiology; Neurocognition; Neurocognitive; Neurocognitive Deficit; Outcome; Outcome Assessment; Outcome Measure; Participant; Phenotype; Population; Preventive Intervention; Process; Prospective Studies; Psychopathology; Psychotic Disorders; Recruitment Activity; Research; Risk; Schizophrenia; Severities; Standardization; Stimulus; Stress; Symptoms; Teenagers; Testing; Time; Variant; Visit; Weight; Youth; affective psychoses; aged; anxious; anxious individuals; base; cognitive ability; cognitive function; cognitive performance; cohort; conotruncal anomaly face syndrome; design; evidence base; executive function; experience; high risk; innovation; instrument; negative affect; neural circuit; neuroimaging; novel; prospective; psychotic symptoms; public health relevance; relating to nervous system; research study; response; standard measure; stress reactivity; trait

 DESCRIPTION (provided by applicant): This project studies risk and protective factors for the very high risk of schizophrenia in chromosome 22q11.2 deletion syndrome (22q), a disorder with a clear genetic etiology but with a complex and variable phenotype. It takes advantage of the unique nature of the 22q population, which has a genetically conferred high risk for schizophrenia yet also provides the rare opportunity for long range prospective developmental studies. Recognizing that, in a population where up to 30% of those affected will develop schizophrenia, 70% with chromosome 22q11.2 deletions do not, the proposed research studies the factors influencing psychosis risk and protection by taking a novel neurodevelopmental approach. It does so in a number of innovative ways that complement existing studies in 22q. Primarily, it asks how prevalent neurocognitive impairment in this disorder creates and interacts with stress and anxiety to affect risk for or protection against the development of psychosis-proneness, before the onset of schizophrenia. Psychosis-proneness will be measured with a novel combination of categorical and dimensional assays of attenuated psychotic symptoms that will be developed by leaders in the field. Our core hypothesis is that psychosis-proneness in 22q, as well as in idiopathic Sz, is developmentally modulated by several critical factors that interact to alter mental health outcomes. Primary is degree of neurocognitive deficit, particularly in executive function and attention. Impairment levels moderate degree of challenge and associated affective states. Cognitive-affective processes interact with variable stress reactivity which in turn, affects anxiety and adaptive function, further moderating the challenge that is experienced. Using a longitudinal cohort-sequential design, novel for 22q, we study how neurocognition, affect, stress and anxiety, interact to alter psychosis-proneness in 22q. We do so by examining the trajectory of a latent construct in individuals aged 12-21 years, each assessed 2-3 times during a 5 year period, to generate and test predictors of psychosis-proneness severity. Based on a model that links neurocognitive and affective processes to explain psychopathology, the proposed research combines cognitive performance and functional neuroimaging data using Event Related Potentials in emotionally "hot" and "cold" task variants with measures of stress hormones and anxiety and adaptive function. Along with structural and functional imaging of neural connectivity these measures provide the variables that will be subjected to factor analysis in order to create, from our latent "risk/protection" construct, specific predictors of degree of psychosis-proneness captured by our novel outcome measure. The relative weights of these predictors will indicate the power of each to identify specific domains of neurobiological functioning that can be further tested as biomarkers of risk and protection, for those with and without 22q. Those same domains will also be targets for identifying or developing validated, evidence-based therapies that can further reduce risk for psychosis.

 描述(由申请人提供)：这个项目研究了染色体22q11.2缺失综合征(22q)精神分裂症的高风险风险和保护因素，这是一种具有明确遗传病因但具有复杂和可变表型的疾病。它利用了22q人群的独特性质，这一人群在遗传上具有患精神分裂症的高风险，但也为长期前瞻性发育研究提供了难得的机会。考虑到高达30%的受影响人群会患上精神分裂症，而染色体22q11.2缺失的人中有70%不会，建议的研究通过采取一种新的神经发育方法来研究影响精神病风险和保护的因素。它以一些创新的方式做到了这一点，这些方式补充了22q中现有的研究。首先，它询问这种障碍中普遍存在的神经认知障碍如何造成压力和焦虑，并与之相互作用，以影响精神分裂症发病前精神病倾向发展的风险或保护。精神病倾向将通过由该领域的领导者开发的减轻精神病症状的分类和维度分析的新组合来衡量。我们的核心假设是，在22Q和特发性Sz中，精神病倾向受到几个关键因素的发育调节，这些因素相互作用，改变心理健康结果。原发是指神经认知缺陷的程度，特别是 在执行功能和注意力方面。损伤程度适中的挑战程度和相关的情感状态。认知-情感过程与可变的应激反应相互作用，而应激反应反过来影响焦虑和适应功能，进一步缓和所经历的挑战。采用纵向队列-序贯设计，新的22q，我们研究了神经认知，影响，压力和焦虑，交互作用，以改变精神病倾向在22q。我们通过检查12-21岁的个体的潜在结构的轨迹来做到这一点，每个人在5年内被评估2-3次，以产生和测试精神倾向严重程度的预测因子。基于一个将神经认知和情感过程联系起来解释精神病理学的模型，这项拟议的研究将认知表现和功能神经成像数据结合在一起，使用事件相关电位在情绪上“热”和“冷”的任务变体中，并测量应激激素、焦虑和适应功能。随着神经连通性的结构和功能成像，这些测量提供了变量，这些变量将接受因子分析，以便从我们潜在的“风险/保护”结构中创建由我们的新结果测量捕获的精神错乱倾向程度的特定预测因子。这些预测指标的相对权重将表明每个预测指标识别神经生物学功能的特定领域的能力，这些领域可以作为风险和保护的生物标记物进一步测试，对于那些有22q和没有22q的人来说。这些领域也将成为识别或开发有效的、基于证据的疗法的目标，这些疗法可以进一步降低精神病的风险。