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）的精神分裂症风险的风险和保护因素，该疾病具有明显的遗传病因，但具有复杂且可变的表型。它利用了22Q人群的独特性质，该人口具有精神分裂症的遗传性高风险，但也为远距离前瞻性发展研究提供了难得的机会。认识到，在最多30％的受影响的人群中会发展精神分裂症，染色体22q11.2缺失没有70％，拟议的研究研究研究了通过采用新型神经发育方法来影响精神病风险和保护的因素。它以多种创新的方式来补充22q中现有研究的方式。首先，它询问这种疾病中这种疾病的普遍神经认知障碍是如何在精神分裂症开始之前影响和保护精神病 - 主持性发展的风险或保护精神病的风险的。精神病 - 主持性将通过分类和尺寸测定的新型组合来衡量，这些测定法对衰减的精神病症状进行了新的结合，这将由该领域的领导者开发。我们的核心假设是，22q以及特发性SZ中的精神病主持性在发展上受到了几个关键因素的发展，这些因素与改变心理健康结果相互作用。主要是神经认知缺陷的程度，特别是 在执行功能和关注中。损伤水平适度的挑战程度和相关的情感状态。认知影响过程与可变的压力反应性相互作用，这反过来又影响焦虑和适应性功能，进一步调节所经历的挑战。我们使用纵向队列的序列设计，即22q的新颖，我们研究神经认知，影响，压力和焦虑如何相互作用，以改变22q中的精神病 - 主持性。我们通过检查12-21岁的个体中潜在结构的轨迹，在5年内评估了2-3次，以产生和测试精神病 - 主持性严重程度的预测指标。基于将神经认知和情感过程联系起来解释心理病理学的模型，该研究使用情感“热”和“冷”任务变体中的事件相关潜力与压力激素以及焦虑和适应性功能的指标结合了认知性能和功能性神经成像数据。与神经连通性的结构和功能成像一起，这些措施提供了将受到因子分析的变量，以创建我们的潜在“风险/保护”构建体，这是我们新颖的结果指标捕获的精神病促进性程度的特定预测指标。这些预测因素的相对权重表明每个人都可以识别神经生物学功能的特定领域，对于有和没有22q的人来说，可以进一步测试是风险和保护的生物标志物。这些相同的领域也将是识别或开发经过验证的循证疗法的目标，可以进一步降低精神病的风险。