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

基本信息

批准号：
7596478
负责人：
VANDANA SHASHI
金额：
$ 31.87万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
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/7596478
关键词：
22q11 22q11 Deletion Syndrome 22q11.2 Achievement Adolescence Age Applications Grants Area Attention Brain Categories Cerebellum Characteristics Child Childhood Chromosomes Complex Corpus Callosum Cross-Sectional Studies Data Development Developmental Delay Disorders Disease Early identification Elderly Enrollment Epidemiology 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 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 Time Variant Verbal Learning Vulnerable Populations base cohort executive function experience follow-up genetic linkage high risk improved innovation medical complication memory process microdeletion neurodevelopment neuropsychological outcome forecast processing speed programs prophylactic prospective psychologic response severe mental illness theories

项目摘要

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（由申请人提供）：22Q11.2染色体缺失综合征（22q11ds）是一种常见的遗传微骨骼综合征，在儿童期为神经发育异常。在成年/青春期晚期已经发现了非常高风险的精神病（25-40％）。早期的神经发育异常与精神病之间的关系尚不清楚。 22q11ds儿童的神经发育和遗传异常的研究将增强对这一脆弱群体以及普通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神经发育障碍。 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与22q11ds。在研究结束时，这些孩子的前驱症状和精神疾病率会增加。我们提出了一项关于神经心理学和神经解剖学变化的纵向研究，以及半合子22q11.2间隔的基因型分析，其中70名非精神病儿童有22q11 ds和70个对照参与者。目的是：1）对神经认知进行纵向评估，包括持续关注，执行功能和口头工作记忆。我们还将测试前驱症状和精神疾病。 2）对磁共振图像（MRI）进行纵向脑形态分析，以量化call体，额叶，颞叶和顶叶和小脑3）基因型特异性单核苷酸多态性（SNP）（SNP），以遗传间隔对应于22q11.2区域的关键删除区域。一个探索目的，我们将在22Q11DS患者中创建单倍型（链接的基因型）。这些发现将与彼此相关，并将预测该子集的前驱症状和精神病诊断率升高。摘要摘要：我们将研究22q11 ds的22q11.2地区学习障碍，大脑结构和遗传变异之间的联系，这是一种患有精神分裂症的高风险的遗传疾病，以了解在这种严重的精神疾病中起作用的因素。