Risk Factors for Psychosis in Chromosome 22q11 Deletion Syndrome

染色体 22q11 缺失综合征精神病的危险因素

• 批准号: 7260866
• 负责人: VANDANA SHASHI
• 金额: $ 33.27万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7260866
• 关键词: 22q11; 22q11 Deletion Syndrome; 22q11.2; Achievement; Adolescence; Age; Applications Grants; Area; Attention; Brain; COMT gene; Catechol O-Methyltransferase; Categories; Cerebellum; Characteristics; Child; Childhood; Chromosomes; Complex; Corpus Callosum; Cross-Sectional Studies; Data; Development; Developmental Delay Disorders; Disease; Early identification; Elderly; Enrollment; Exhibits; Factor Analysis; Family history of; General Population; Genes; Genetic; Genetic Markers; Genotype; Grant; Haplotypes; Hereditary Disease; Heritability; Impaired cognition; Impairment; Incidence; Individual; Inherited; Intelligence; Intervention; Investigation; Learning Disabilities; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Memory; Mental disorders; Modeling; Molecular Abnormality; Moods; Nature; Neuroanatomy; Neurocognition; Neurocognitive; Neurodevelopmental Disorder; Outcome Measure; Parietal Lobe; Participant; Pathogenesis; Patients; Play; Population Study; Principal Investigator; Probability; Prospective Studies; Psychiatric Diagnosis; Psychotic Disorders; Range; Rate; Relative (related person); Reporting; Research Personnel; Rest; Retrospective Studies; Risk; Risk Factors; Role; Sampling; Schizophrenia; Schizotypal Personality Disorder; Short-Term Memory; Signs and Symptoms; Single Nucleotide Polymorphism; Structure; Subgroup; Symptoms; Syndrome; Testing; Thinking; Time; Variant; Verbal Learning; base; cohort; executive function; experience; follow-up; genetic linkage; improved; innovation; medical complication; memory process; microdeletion; neurodevelopment; neuropsychological; outcome forecast; processing speed; programs; prophylactic; prospective; psychologic; response; severe mental illness; theories

DESCRIPTION (provided by applicant): Chromosome 22q11.2 Deletion Syndrome (22q11DS) is a common genetic microdeletion syndrome, with neurodevelopmental abnormalities in childhood. A remarkably high-risk of psychoses (25-40%) has been identified in adulthood/late adolescence. The relationship between the early neurodevelopmental abnormalities and psychoses in later life is unclear. The study of the neurodevelopmental and genetic abnormalities in children with 22q11DS would enhance the understanding of the trajectory that leads to schizophrenia in this vulnerable group as well as in the general population, since schizophrenia is thought to be a neurodevelopmental disorder. Our hypotheses are that the subset of 22q11DS children that is most vulnerable to psychosis would have: 1) pronounced and worsening abnormalities of neurocognition 2) pronounced and progressive morphological brain abnormalities of the frontal, temporal and parietal lobes, cerebellum and the corpus callosum 3) hemizygous genotypes within the 22q11.2 region that will be distinct from the rest with 22q11DS. These children would have an increased rate of prodromal symptoms and psychiatric disorders at the end of the study. We propose a longitudinal study of the neuropsychological and neuroanatomical changes, and genotype analysis of the hemizygous 22q11.2 interval in a cohort of 70 nonpsychotic children with 22q11 DS and 70 control participants. The aims are to: 1) Conduct a longitudinal assessment of neurocognition, including sustained attention, executive function and verbal working memory. We will also test for prodromal symptoms and psychiatric disorders. 2) Perform longitudinal brain morphometric analyses on magnetic resonance images (MRI) to quantify the corpus callosum, frontal, temporal, and parietal lobes and the cerebellum 3) Genotype specific single nucleotide polymorphisms (SNPs) in the genetic interval corresponding to the critical deleted area of the 22q11.2 region. An an exploratory aim, we will create haplotypes (linked genotypes) in the 22q11DS patients. These findings will be correlated with one another and will be predictive of the subset that will have elevated rates of prodromal symptoms and psychiatric diagnoses. Lay Summary: We will study the links between learning disabilities, brain structure and hereditary variants in the 22q11.2 region in children with 22q11 DS, a genetic condition with a high risk of schizophrenia, to understand the factors that play a role in this severe mental illness.

描述（申请人提供）：染色体22q11.2缺失综合征（22 q11 DS）是一种常见的遗传性微缺失综合征，在儿童期出现神经发育异常。在成年期/青春期后期，精神病的风险非常高（25-40%）。早期神经发育异常与晚年精神病之间的关系尚不清楚。对22 q11 DS儿童神经发育和遗传异常的研究将增强对导致这一弱势群体以及一般人群中精神分裂症的轨迹的理解，因为精神分裂症被认为是一种神经发育障碍。我们的假设是，22 q11 DS儿童中最易患精神病的亚组将具有：1）明显且恶化的神经认知异常2）额叶、颞叶和顶叶、小脑和胼胝体的明显且进行性的脑形态异常3）22q11.2区域内的半合子基因型，其与22 q11 DS的其余部分不同。在研究结束时，这些儿童的前驱症状和精神疾病的发生率会增加。我们提出了一个纵向研究的神经心理学和神经解剖学的变化，半合子22q11.2间隔的基因型分析在一个队列的70名非精神病儿童与22 q11 DS和70名对照参与者。目的是：1）进行神经认知的纵向评估，包括持续注意力，执行功能和言语工作记忆。我们还要检查前驱症状和精神障碍。2)对磁共振图像（MRI）进行纵向脑形态测量分析，以量化胼胝体、额叶、颞叶和顶叶以及小脑3）与22q11.2区域的关键缺失区相对应的遗传间隔中的基因型特异性单核苷酸多态性（SNP）。作为一个探索性的目标，我们将在22 q11 DS患者中创建单倍型（连锁基因型）。这些发现将相互关联，并将预测具有前驱症状和精神病诊断率升高的子集。概述：我们将研究22 q11 DS儿童的学习障碍，大脑结构和22q11.2区域的遗传变异之间的联系，这是一种具有精神分裂症高风险的遗传疾病，以了解在这种严重精神疾病中发挥作用的因素。