THE GENETICS OF ENDOPHENOTYPES AND SCHIZOPHRENIA

内表型和精神分裂症的遗传学

• 批准号: 7718121
• 负责人: Larry J Siever
• 金额: $ 1.03万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718121
• 关键词: Affect; All Sites; Auditory; Binding Sites; Blood specimen; Clinical; Computer Retrieval of Information on Scientific Projects Database; DNA; DSM-IV; Diagnosis; Diagnostic; Disease; Event-Related Potentials; Eye; Eye Movements; Family; Family history of; Family member; Funding; Genetic; Grant; Healthcare Systems; Institution; Interview; Learning; Measures; Memory; Mental disorders; Neurocognitive; Neurocognitive Deficit; Numbers; Performance; Protocols documentation; Purpose; Recruitment Activity; Relative (related person); Research; Research Personnel; Resources; Risk; Running; Schizophrenia; Short-Term Memory; Site; Source; Time; Training; United States National Institutes of Health; Urban Hospitals; endophenotype; genetic analysis; member; neurophysiology; proband; response; transmission process; visual stimulus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this research is to learn more about the genetic transmission of schizophrenia by attempting to identify how specific sub-clinical phenomena associated with the disorder, commonly referred to as the endophenotype, may run in families of a schizophrenic proband. A number of different studies have shown various neurophysiological and neurocognitive deficits to be associated with schizophrenia. Neurophysiological deficits include abnormal event related potentials, inhibited startle response and eye movements. Neurocognitive deficits include poor performance on both verbal and working memory. These same deficits are in seen in unaffected relatives of schizophrenics, which indicated that they might reflect part of the heritable risk for the illness. This conclusion is reinforced by findings of the deficits in non-psychotic, unmedicated schizophrenics and schizotypals. This study will recruit families with at least one member who has schizophrenia. Trained raters will then conduct a family history interview using the Family Interview for Genetic Studies (FIGS). We will also interview each family member individually using the Diagnostic Interview for Genetic Studies (DIGS) to assess for the presence or absence of psychiatric disorders. Once a diagnosis of schizophrenia is confirmed for at least one member of the family, we then conduct the following noninvasive, minimal risk protocol on all members of the family. There are three neurophysiological and three neurocognitive assessments included in this battery. The neurophysiological assessments measure deficits in response to various auditory and visual stimuli. The three neurocognitive assessments measure deficits in eye tracking, verbal memory and working memory. We will also collect blood samples from each participating family member, which will be used for DNA extraction and genetic analysis. Our collaborative team is composed of investigators at seven sites. Within a time period of five years, the combined sites will recruit 1680 subjects affected with DSM-IV schizophrenia and 525 normal subjects. All sites will recruit the subjects from large regional health care systems and/or large metropolitan hospitals. Findings of heritable deficits in specific measures will be used to guide further studies of schizophrenia genetics.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的目的是通过试图确定与精神分裂症相关的特定亚临床现象，通常被称为内表型，在精神分裂症先证者的家庭中运行，以了解更多关于精神分裂症的基因传播。许多不同的研究表明，各种神经生理和神经认知缺陷与精神分裂症有关。神经生理学缺陷包括异常事件相关电位、惊吓反应抑制和眼球运动。神经认知缺陷包括在语言和工作记忆方面表现不佳。这些缺陷在精神分裂症患者的未受影响的亲属中也可以看到，这表明它们可能反映了疾病的部分遗传风险。这一结论被非精神病、未用药的精神分裂症患者和分裂型患者的缺陷所证实。 这项研究将招募至少有一名成员患有精神分裂症的家庭。然后，训练有素的评分员将使用遗传学家庭访谈(Figs)进行家族史访谈。我们还将使用遗传学诊断访谈(DIGS)单独采访每个家庭成员，以评估是否存在精神障碍。一旦至少有一名家庭成员被确诊为精神分裂症，我们就会对所有家庭成员进行以下无创、风险最低的方案。这组测试包括三项神经生理评估和三项神经认知评估。神经生理学评估衡量的是对各种听觉和视觉刺激的反应缺陷。这三项神经认知评估衡量的是眼睛跟踪、言语记忆和工作记忆方面的缺陷。我们还将收集每个参与家庭成员的血液样本，用于DNA提取和基因分析。 我们的合作团队由七个地点的调查人员组成。在五年的时间内，联合地点将招募1680名患有DSM-IV精神分裂症的患者和525名正常受试者。所有网站都将从大型地区性医疗保健系统和/或大型大都市医院招募受试者。具体措施中可遗传缺陷的发现将被用于指导精神分裂症遗传学的进一步研究。