Suicidal Behavior in Mood Disorders:Genes and Intermediate Phenotypes

情绪障碍中的自杀行为：基因和中间表型

基本信息

批准号：
8116622
负责人：
Joseph John Mann
金额：
$ 55.31万
依托单位：
NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-19 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8116622
关键词：
Accounting Adoption Affect Aggressive behavior Amino Acids Autopsy Behavioral Bioinformatics Biological Assay Bipolar Disorder Brain Canada Candidate Disease Gene Cause of Death Child Abuse Childhood Clinical Clinical Research Code Collaborations Complex Control Groups Cost Savings Data Databases Depressed mood Depression and Suicide Development Diagnosis Disease susceptibility Drops Ensure Environment Epidemiology Family Feeling hopeless Feeling suicidal Foundations Frequencies Funding Future Gene Expression Gene Frequency Genes Genetic Genetic Polymorphism Genetic Variation Genome Genotype Germany Haplotypes Health Heritability Human Genetics Impulsivity Individual Lead Life Life Stress Location Major Depressive Disorder Maps Measurement Measures Mediating Mental Depression Mental Health Mental disorders Methods Minor Modeling Mood Disorders New York New York City Pathogenesis Pattern Personality Disorders Phenotype Predisposition Price Recording of previous events Reporting Research Institute Risk Risk Factors Role Sampling Screening procedure Serotonin Severities Sexual abuse Site Stress Structural Genes Substance Use Disorder Sudden Death Suicide Suicide attempt Surveys Technology Testing Time Twin Multiple Birth Twin Studies Universities Variant Work abuse neglect accomplished suicide base case control clinical phenotype cost density disorder control early childhood endophenotype experience gene function genome wide association study healthy volunteer physical abuse sample collection suicidal suicidal act suicidal behavior suicidal patient suicide attempter trait transmission process

项目摘要

DESCRIPTION (provided by applicant): This collaborative R01 involves three sites: New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., in New York City, USA (Mann), McGill University in Montreal, Canada (Turecki) and University of Munich, Germany (Rujescu) to examine the complex genetic basis of suicidal behavior. We have contributed to the original observations showing that suicide and nonfatal suicide attempts have biologic changes that are distinct from those of major psychiatric disorders that underlie suicide such as major depressive disorder or bipolar disorder. We have reported candidate gene associations that are independently associated with mood disorders or with suicide attempts. We believe the field is ready for a major effort to survey the genome to seek genes associated with suicidal behavior that are independent of the major psychiatric illnesses. We have developed and tested a potential predictive stress-diathesis model of suicidal behavior derived from a comprehensive assessment of risk factors. Depressed individuals with prominent (1) pessimism and (2) severity of life-time aggression/impulsivity are at greater risk for suicidal behavior and the effects are additive. These clinical phenotypic components can be measured in the field in patients and suicides. We now propose to use genome-wide screens to identify candidate genes and conserved haplotype blocks within those genes 4000 cases that span the higher severity range of suicidal behavior, namely completed suicide and attempted suicide compared to both psychiatrically matched controls and to healthy volunteers. We have data on Axis I and Axis II diagnoses and data on lifetime aggression scores and current severity of depression to permit assessment of these potential etiological factors and potential behavioral endophenotypes. We have data on childhood reported histories of physical or sexual abuse which will be a focus for an exploratory gene-early environment interaction analysis. Causal SNPs will be further identified by sequencing the most promising gene segments. PUBLIC HEALTH RELEVANCE: The predisposition to suicidal behavior is substantially determined by genetic factors independent of those associated with major psychiatric disorders. This study will screen the genome in the largest collection of samples ever assembled for such a study of suicidal behavior in order to identify the responsible genes.

描述（由申请人提供）：该合作 R01 涉及三个地点：美国纽约市的纽约州精神病学研究所/心理卫生研究基金会 (Mann)、加拿大蒙特利尔的麦吉尔大学 (Turecki) 和大学德国慕尼黑的 (Rujescu) 研究自杀行为的复杂遗传基础。我们对最初的观察结果做出了贡献，表明自杀和非致命性自杀企图具有与导致自杀的主要精神疾病（例如重度抑郁症或双相情感障碍）不同的生物学变化。我们已经报道了与情绪障碍或自杀企图独立相关的候选基因关联。我们相信该领域已经准备好进行重大努力来调查基因组，以寻找与自杀行为相关的基因，这些基因与主要精神疾病无关。我们开发并测试了一种潜在的自杀行为预测压力素质模型，该模型源自对风险因素的综合评估。具有显着的（1）悲观情绪和（2）一生中严重的攻击/冲动的抑郁症患者自杀行为的风险更大，而且其影响是相加的。这些临床表型成分可以在患者和自杀者的现场进行测量。我们现在建议使用全基因组筛选来识别候选基因和这些基因中的保守单倍型块。4000个案例涵盖了自杀行为的较高严重程度范围，即与精神匹配的对照和健康志愿者相比，完成自杀和企图自杀。我们拥有有关 Axis I 和 Axis II 诊断的数据以及有关终生攻击评分和当前抑郁严重程度的数据，以便评估这些潜在的病因和潜在的行为内表型。我们拥有有关儿童报告的身体或性虐待历史的数据，这将成为探索性基因与早期环境相互作用分析的重点。通过对最有希望的基因片段进行测序，将进一步鉴定因果 SNP。公共卫生相关性：自杀行为的倾向在很大程度上是由遗传因素决定的，独立于与主要精神疾病相关的因素。这项研究将在自杀行为研究中收集的最大样本中筛选基因组，以确定相关基因。