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: 9748594
• 负责人: Kathleen Angkustsiri
• 金额: $ 62.99万
• 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 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9748594
• 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; DiGeorge Syndrome; 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; Neurodevelopmental Disorder; Outcome; Outcome Assessment; Outcome Measure; Participant; Phenotype; Population; Preventive Intervention; Process; Prospective Studies; Psychopathology; Psychotic Disorders; Research; Risk; Risk Factors; Schizophrenia; Severities; Standardization; Stimulus; Stress; Structure; Symptoms; Teenagers; Testing; Time; Variant; Visit; Weight; Youth; affective psychoses; aged; allostatic load; anxious; anxious individuals; base; cognitive ability; cognitive function; cognitive performance; cohort; design; evidence base; executive function; experience; high risk; innovation; instrument; negative affect; network models; neural circuit; neuroimaging; novel; predictive test; prospective; protective factors; psychiatric symptom; psychotic symptoms; public health relevance; recruit; relating to nervous system; research study; response; standard measure; stress reactivity; stress state; 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）：该项目研究染色体 22q11.2 缺失综合征 (22q) 中精神分裂症极高风险的风险和保护因素，这种疾病具有明确的遗传病因，但表型复杂多变。它利用了 22q 群体的独特性质，该群体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。认识到，在受影响的人群中，高达 30% 的人会患上精神分裂症，而 70% 的染色体 22q11.2 缺失的人不会患上精神分裂症，因此拟议的研究通过采用一种新颖的神经发育方法来研究影响精神病风险和保护的因素。它通过多种创新方式来实现这一目标，这些方式补充了 22q 的现有研究。主要探讨的是，在精神分裂症发作之前，这种疾病中普遍存在的神经认知障碍如何产生压力和焦虑并与之相互作用，从而影响精神病倾向的风险或防止其发生。精神病倾向将通过该领域领导者开发的减轻精神病症状的分类和维度分析的新颖组合来测量。我们的核心假设是，22q 以及特发性 Sz 的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。主要是神经认知缺陷的程度，特别是 执行功能和注意力。障碍水平中等程度的挑战和相关的情感状态。认知情感过程与可变的压力反应相互作用，进而影响焦虑和适应功能，进一步缓解所经历的挑战。我们使用 22q 新颖的纵向队列序贯设计，研究神经认知、情感、压力和焦虑如何相互作用来改变 22q 的精神病倾向。我们通过检查 12-21 岁个体的潜在结构轨迹来做到这一点，每个人在 5 年期间评估 2-3 次，以生成和测试精神病倾向严重程度的预测因子。基于连接神经认知和情感过程来解释精神病理学的模型，拟议的研究将认知表现和功能神经影像数据结合起来，使用情绪“热”和“冷”任务变体中的事件相关电位与压力激素、焦虑和适应功能的测量。除了神经连接的结构和功能成像之外，这些测量还提供了将进行因子分析的变量，以便从我们潜在的“风险/保护”结构中创建我们的新结果测量捕获的精神病倾向程度的特定预测因子。这些预测因子的相对权重将表明每个预测因子识别神经生物学功能特定领域的能力，对于有或没有 22q 的人，可以将其作为风险和保护的生物标志物进行进一步测试。这些相同的领域也将成为识别或开发经过验证的、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。