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:8117654
- 负责人:
- 金额:$ 6.81万
- 依托单位:
- 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:
- 关键词:AccountingAdoptionAffectAggressive behaviorAmino AcidsAutopsyBehavioralBioinformaticsBiological AssayBipolar DisorderBrainCanadaCandidate Disease GeneCause of DeathChild AbuseChildhoodClinicalClinical ResearchCodeCollaborationsComplexControl GroupsCost SavingsDataDatabasesDepressed moodDepression and SuicideDevelopmentDiagnosisDisease susceptibilityDropsEnsureEnvironmentEpidemiologyFamilyFeeling hopelessFeeling suicidalFoundationsFrequenciesFundingFutureGene ExpressionGene FrequencyGenesGeneticGenetic PolymorphismGenetic VariationGenomeGenotypeGermanyHaplotypesHealthHeritabilityHuman GeneticsImpulsivityIndividualLeadLifeLife StressLocationMajor Depressive DisorderMapsMeasurementMeasuresMediatingMental DepressionMental HealthMental disordersMethodsMinorModelingMood DisordersNew YorkNew York CityPathogenesisPatternPersonality DisordersPhenotypePredispositionPriceRecording of previous eventsReportingResearch InstituteRiskRisk FactorsRoleSamplingScreening procedureSerotoninSeveritiesSexual abuseSiteStressStructural GenesSubstance Use DisorderSudden DeathSuicideSuicide attemptSurveysTechnologyTestingTimeTwin Multiple BirthTwin StudiesUniversitiesVariantWorkabuse neglectaccomplished suicidebasecase controlclinical phenotypecostdensitydisorder controlearly childhoodendophenotypeexperiencegene functiongenome wide association studyhealthy volunteerphysical abusesample collectionsuicidalsuicidal actsuicidal behaviorsuicidal patientsuicide attemptertraittransmission 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):该协作R01涉及三个站点:纽约州精神病学研究所/精神卫生研究基金会,美国纽约市,美国纽约市(Mann),蒙特利尔的麦吉尔大学(TURECKI)(TURECKI)和德国慕尼黑大学(DEM MUNICH),德国大学(RUJESCU),以检查复杂的遗传基础,以进行复杂的遗传基础。我们为最初的观察做出了贡献,表明自杀和非致命自杀企图具有生物学变化,这些变化与主要的自杀症(例如重大抑郁症或双相情感障碍)的主要精神病患者不同。我们报道了与情绪障碍或自杀企图独立相关的候选基因关联。我们认为,该领域已准备好进行重大努力来调查基因组,以寻求与自杀行为相关的基因,这些基因独立于主要的精神病疾病。我们已经开发并测试了自杀行为的潜在预测应力分析模型,该模型是根据风险因素的全面评估得出的。沮丧的人(1)悲观主义和(2)生活时间侵略/冲动的严重程度具有更大的自杀行为风险,其影响是加性的。这些临床表型成分可以在患者和自杀的现场测量。现在,我们建议使用全基因组筛查来鉴定这些基因中的候选基因和保守的单倍型块4000例,这些病例跨越了自杀行为的严重程度较高,即与精神上匹配的控制和健康的志愿者相比,自杀和未遂自杀。我们拥有有关轴I和轴II诊断的数据以及有关终生攻击得分以及当前抑郁症的严重程度的数据,以评估这些潜在的病因学因素和潜在的行为内表型。我们有关于童年报告的身体或性虐待病史的数据,这将成为探索性基因与环境相互作用分析的重点。通过测序最有希望的基因段,将进一步识别因果SNP。公共卫生相关性:自杀行为的易感性主要取决于与与主要精神疾病相关的因素无关的遗传因素。这项研究将在有史以来最大的样本集合中筛选基因组,以进行自杀行为,以识别负责任的基因。
项目成果
期刊论文数量(0)
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GUSTAVO TURECKI其他文献
GUSTAVO TURECKI的其他文献
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{{ truncateString('GUSTAVO TURECKI', 18)}}的其他基金
2/2 Large-scale, single-cell characterization of molecular and cellular networks of mood regulation circuitry in major depressive disorder
2/2 重度抑郁症情绪调节回路的分子和细胞网络的大规模单细胞表征
- 批准号:
10745412 - 财政年份:2023
- 资助金额:
$ 6.81万 - 项目类别:
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
- 批准号:
8321825 - 财政年份:2008
- 资助金额:
$ 6.81万 - 项目类别:
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
- 批准号:
7912904 - 财政年份:2008
- 资助金额:
$ 6.81万 - 项目类别:
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
- 批准号:
7689340 - 财政年份:2008
- 资助金额:
$ 6.81万 - 项目类别:
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