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

基本信息

批准号：
8908496
负责人：
TONY J SIMON
金额：
$ 75.6万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
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/8908496
关键词：
18 year old 21 year old 22q 22q11.2 Adolescence Adolescent and Young Adult Affect Affective Age Anxiety Attention Attenuated Biological Assay Biological Markers Brain Chromosomes Chronic stress Clinical Cognition Cognitive Cognitive deficits Complement Complex Data Development Disease Early identification 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 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 Relative (related person)Research Risk Schizophrenia Severities Stimulus Stress Symptoms Syndrome Teenagers Testing Time Variant Visit Weight Youth affective psychoses aged anxious anxious individuals base chromosome 22q deletion syndrome cognitive ability cognitive function cognitive performance cohort design enhancing factor evidence base executive function experience high risk innovation instrument neural circuit neuroimaging novel prospective psychotic symptoms public health relevance relating to nervous system research study response standard measure stress reactivity trait

项目摘要

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，该疾病具有明确的遗传病因，但具有复杂且多变的表型。 22q 群体的独特性质，从遗传角度来看，该群体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。高达 30% 的受影响人群会患上精神分裂症，而 70% 的染色体 22q11.2 缺失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。补充 22q 现有研究的创新方法首先，它询问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，从而影响患上这种疾病的风险或防止其发生。精神病倾向，在精神分裂症发作之前，将通过该领域的领导者开发的一种新颖的减轻精神病症状的分类和维度分析来测量精神病倾向。以及特发性 Sz 中，发育受到几个相互作用改变心理健康结果的关键因素的调节，特别是神经认知缺陷的程度。执行功能和注意力的损伤水平中等程度的挑战和相关的情感状态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。 22q 的设计新颖，我们研究神经认知、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实现这一目标。 5 年期间，每次评估 2-3 次，以生成和测试精神病倾向严重程度的预测因子。该研究基于神经联系认知和情感过程来解释精神病理学的模型，将认知表现和功能神经影像数据结合起来。情绪“热”和“冷”任务变体中的事件相关电位以及应激激素、焦虑和适应功能的测量以及神经连接的结构和功能成像，这些测量提供了将进行因子分析的变量。根据我们潜在的“风险/保护”结构，创建由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的特定领域的能力，这些领域可以进一步进行。对于有或没有 22q 的人来说，这些相同的域也将作为风险和保护的生物标志物进行测试，也将成为识别可进一步降低精神病风险的开发或经过验证的循证疗法的目标。