Familial Schizophrenia Spectrum Personality Disorders

家族性精神分裂症谱系人格障碍

• 批准号: 7261216
• 负责人: GUNVANT K THAKER
• 金额: $ 48.34万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/7261216
• 关键词: Affect; Age; Behavioral; Case-Control Studies; Clinical; Cognitive; Collection; Communities; County; Data; Development; Diagnosis; Disease; Environmental Risk Factor; Exhibits; Factor Analysis; Failure; Family; Family Study; Family history of; Family member; First Degree Relative; Frequencies; Future; Genes; Genetic; Genetic Carriers; Goals; Heritability; Impairment; Individual; Language; Light; Measures; Methods; Mitochondrial Carnitine Palmitoyltransferase Pathway; Modeling; Neurocognitive Deficit; Neurons; Numbers; Odds Ratio; Patients; Pattern; Performance; Personality; Personality Disorders; Persons; Phenotype; Prevalence; Prevention Research; Procedures; Psychopathology; Psychotic Disorders; Purpose; Race; Rate; Recruitment Activity; Relative (related person); Research; Risk; Sampling; Schizophrenia; Score; Short-Term Memory; Smooth Pursuit; Solutions; Standards of Weights and Measures; Structure; Symptoms; TNFRSF5 gene; Telephone; Testing; Validation; Visual attention; base; case control; clinical Diagnosis; clinical phenotype; disorder risk; endophenotype; functional disability; gene environment interaction; genetic variant; long term memory; neurophysiology; predictive pursuit; proband; processing speed; sensory gating; sex; trend

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）：识别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到行为和功能障碍的因果路径。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组合，因此以不同的表型集合为特征，每种表型都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发现可能会有所不同，这可能解释了重复复制已确定的疾病位点的失败。根据临床诊断来确定谁会受到影响，也忽略了一些亲属虽然在临床上未受影响，但也携带疾病风险的可能性。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，迫切需要能够反映疾病风险特定方面的表型。标记疾病风险特定方面的内表型的识别、验证和应用对未来的遗传研究、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，以确认假定的神经生理和认知表型与精神分裂症倾向性之间的关联，并确定这些缺陷是否与排除SSP症状本身影响的病例亲属中精神分裂症、人格谱（SSP）症状的存在有关。我们建议检查神经生理/认知测量之间的关系，以确定哪些缺陷反映了共同的潜在表型，哪些代表了疾病风险的独立方面。我们将根据先证者中是否存在缺陷来确定病例亲属中单一缺陷和复合缺陷的差异风险。将检查家庭内部的相关措施，以得出遗传力的估计，并检查遗传和共同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）。对于每个先证者，我们将使用有针对性的电话呼叫（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且符合条件的对照亲属（300人）。我们还将从社区中招募一组没有精神障碍家族史但表现出SSP的人，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，并使用标准的家庭病例对照分析程序进行组间比较。

项目成果

Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes.

• DOI: 10.1001/archgenpsychiatry.2011.71
• 发表时间: 2011-07
• 期刊: ARCHIVES OF GENERAL PSYCHIATRY
• 作者: Wonodi, Ikwunga;Stine, O. Colin;Sathyasaikumar, Korrapati V.;Roberts, Rosalinda C.;Mitchell, Braxton D.;Hong, L. Elliot;Kajii, Yasushi;Thaker, Gunvant K.;Schwarcz, Robert
• 通讯作者: Schwarcz, Robert

Individualized brain inhibition and excitation profile in response to paired-pulse TMS.

• DOI: 10.1080/00222895.2013.850401
• 发表时间: 2014
• 期刊: Journal of motor behavior
• 影响因子: 1.4
• 作者: Du X;Summerfelt A;Chiappelli J;Holcomb HH;Hong LE
• 通讯作者: Hong LE

Neurophysiological endophenotypes across bipolar and schizophrenia psychosis.

• DOI: 10.1093/schbul/sbn049
• 发表时间: 2007-11
• 期刊: Schizophrenia bulletin
• 影响因子: 6.6
• 作者: G. Thaker

Saccadic eye movement abnormalities in relatives of patients with schizophrenia.

精神分裂症患者亲属的眼球扫视运动异常。

• DOI: 10.1016/s0920-9964(99)00193-0
• 发表时间: 2000
• 期刊: Schizophrenia research
• 影响因子: 4.5
• 作者: Thaker,GK;Ross,DE;Cassady,SL;Adami,HM;Medoff,DR;Sherr,J
• 通讯作者: Sherr,J

Dopamine transporter polymorphism modulates oculomotor function and DAT1 mRNA expression in schizophrenia.

• DOI: 10.1002/ajmg.b.30811
• 发表时间: 2009-03-05
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
• 影响因子: 2.8
• 作者: Wonodi, Ikwunga;Hong, L. Elliot;Stine, O. Colin;Mitchell, Braxton D.;Elliott, Amie;Roberts, Rosalinda C.;Conley, Robert R.;McMahon, Robert P.;Thaker, Gunvant K.
• 通讯作者: Thaker, Gunvant K.