Familial Schizophrenia Spectrum Personality Disorders
家族性精神分裂症谱系人格障碍
基本信息
- 批准号:7090576
- 负责人:
- 金额:$ 50.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1993
- 资助国家:美国
- 起止时间:1993-05-01 至 2008-06-30
- 项目状态:已结题
- 来源:
- 关键词:adult human (21+)age differenceattentionbehavior testbiomarkerclinical researchdata collection methodology /evaluationfamily geneticsgenetic susceptibilityhuman subjectmemoryneurophysiologyneuropsychological testspersonality disordersphenotypeproblem solvingracial /ethnic differencesaccadesschizophreniasmooth pursuit eye movementverbal behavior
项目摘要
DESCRIPTION (provided by applicant): Identifying disease-related genetic effects is a major focus in schizophrenia research. Efforts have been multifaceted with the ultimate goal to describe a causal path from specific genetic variants to changes in neuronal functioning to behavioral and functional impairments. The schizophrenia diagnosis likely reflects a heterogeneous combination of several such causal paths,and is therefore characterized by a varying collection of phenotypes each associated with specific neurocognitive deficits reflecting the effects of a small subset of genes. Thus genetic findings based on the clinical phenotype are likely to vary, which may explain repeated failures to replicate identified disease loci. Defining who is affected based on the clinical diagnosis also ignores the likelihood that some relatives, although clinically unaffected, also carry aspects of disease risk. Environmental factors are also implicated, adding to the etiologic complexity of the disease. In light of these complexities there is a critical need for phenotypes that reflect specific aspects of disease risk. The identification, validation, and application of endophenotypes that mark specific aspects of disease risk has important implications for future genetic studies, studies examining the interaction of genes and environment, studies ofpathophysiology, and prevention research. We propose to conduct a family case-control study to confirm the association(s) between putative neurophysiological and cognitive phenotypes and schizophrenia liability and to determine if these deficits are associated with the presence of schizophrenia,spectrum personality (SSP) symptoms among case relatives ruling out the effects of SSP symptoms per se. We propose to examine the relationships among neurophysiological/cognitive measures to determine which deficits reflect a common underlying phenotype and which represent independent aspects of disease risk. We will determine the differential risk of single and composite deficits among case relatives based on the presence/absence of deficits in case probands. Within family correlations for implicated measures will be examined to derive estimates of heritability and to examine the relative contributions of genetic and shared environmental effects. We also propose to examine the relationships between neurophysiological phenotypes and schizophrenia-related symptom domains. We plan to recruit 120 patients and all available first-degree relatives (300, 60 with SSP). For each case proband, we will identify an age (+ 3 yrs), sex, race, county matched control proband using targeted telephone calling (TTC) procedures. We will recruit all available and eligible control relatives (300). We will also recruit a separate group of persons from the community who exhibit SSP in the absence of a family history of psychotic disorders in order to examine the effects of SSP symptoms per se. Clinical information, electrophysiological and cognitive measures will be collected and compared among the groups using standard family case control analytic procedures.
描述(由申请人提供):确定疾病相关的遗传效应是精神分裂症研究的主要焦点。努力是多方面的,最终目标是描述从特定遗传变异到神经元功能变化再到行为和功能障碍的因果关系。精神分裂症的诊断可能反映了几个这样的因果路径的异质性组合,因此其特征在于不同的表型集合,每个表型与特定的神经认知缺陷相关,反映了一小部分基因的影响。因此,基于临床表型的遗传学发现可能会有所不同,这可能解释了重复失败的复制确定的疾病位点。根据临床诊断确定谁受影响也忽略了一些亲属的可能性,尽管临床上未受影响,但也携带疾病风险。环境因素也有牵连,增加了疾病的病因复杂性。鉴于这些复杂性,迫切需要反映疾病风险特定方面的表型。内表型的识别、验证和应用标志着疾病风险的特定方面,对未来的遗传学研究、基因与环境相互作用的研究、病理生理学研究和预防研究具有重要意义。我们建议进行一项家庭病例对照研究,以确认推定的神经生理和认知表型与精神分裂症易感性之间的关联,并确定这些缺陷是否与精神分裂症的存在有关,排除SSP症状本身的影响。我们建议检查神经生理/认知措施之间的关系,以确定哪些赤字反映了一个共同的潜在表型,并代表独立的方面的疾病风险。我们将根据先证者是否存在缺陷来确定病例亲属中单一和复合缺陷的不同风险。在家庭内的相关性牵连的措施将被检查,以获得估计的遗传力,并检查遗传和共享的环境影响的相对贡献。我们还建议检查神经生理表型和精神分裂症相关症状域之间的关系。我们计划招募120名患者和所有可用的一级亲属(300人,60人患有SSP)。对于每例先证者,我们将使用目标电话(TTC)程序确定年龄(± 3岁)、性别、种族、县匹配的对照先证者。我们将招募所有可用和合格的对照亲属(300例)。我们也会从社区中招募一组没有精神病家族史的SSP患者,以检查SSP症状本身的影响。将收集临床信息、电生理和认知测量,并使用标准家庭病例对照分析程序在各组之间进行比较。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('GUNVANT K THAKER', 18)}}的其他基金
Proof of concept study of negative symptoms in schizophrenia
精神分裂症阴性症状的概念验证研究
- 批准号:
8080312 - 财政年份:2010
- 资助金额:
$ 50.71万 - 项目类别:
FAMILIAL SCHIZOPHRENIA AND SPECTRUM PERSONALITY DISORDERS
家族性精神分裂症和谱系人格障碍
- 批准号:
7951145 - 财政年份:2009
- 资助金额:
$ 50.71万 - 项目类别:
Proof of concept study of negative symptoms in schizophrenia
精神分裂症阴性症状的概念验证研究
- 批准号:
7483504 - 财政年份:2008
- 资助金额:
$ 50.71万 - 项目类别:
Bipolar & Schizophrenia Consortium for Parsing Intermediate Phenotypes
双极性
- 批准号:
7678495 - 财政年份:2007
- 资助金额:
$ 50.71万 - 项目类别:
Bipolar & Schizophrenia Consortium for Parsing Intermediate Phenotypes
双极性
- 批准号:
7906718 - 财政年份:2007
- 资助金额:
$ 50.71万 - 项目类别:
FAMILIAL SCHIZOPHRENIA AND SPECTRUM PERSONALITY DISORDERS
家族性精神分裂症和谱系人格障碍
- 批准号:
7608137 - 财政年份:2007
- 资助金额:
$ 50.71万 - 项目类别:
Bipolar & Schizophrenia Consortium for Parsing Intermediate Phenotypes
双极性
- 批准号:
7387205 - 财政年份:2007
- 资助金额:
$ 50.71万 - 项目类别:
NEUROPHYSIOLOGY STUDIES IN SCHIZOPHRENIA AND RELATED DISORDERS
精神分裂症及相关疾病的神经生理学研究
- 批准号:
7376922 - 财政年份:2006
- 资助金额:
$ 50.71万 - 项目类别:
FAMILIAL SCHIZOPHRENIA AND SPECTRUM PERSONALITY DISORDERS
家族性精神分裂症和谱系人格障碍
- 批准号:
7376950 - 财政年份:2006
- 资助金额:
$ 50.71万 - 项目类别:
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