THE GENETICS OF ENDOPHENOTYPES AND SCHIZOPHRENIA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本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）如何在精神分裂症先证者的家庭中运行来了解更多关于精神分裂症的遗传传递。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。神经生理缺陷包括事件相关电位异常、惊吓反应抑制和眼动。神经认知缺陷包括语言和工作记忆的不良表现。同样的缺陷也出现在精神分裂症患者未受影响的亲属身上，这表明他们可能反映了这种疾病的部分遗传风险。这一结论在非精神病性、未用药的精神分裂症患者和分裂型患者中得到了进一步的证实。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研究家庭访谈（FIGS）进行家族史访谈。我们还将使用遗传研究诊断访谈（DIGS）对每个家庭成员进行单独访谈，以评估是否存在精神疾病。一旦至少有一位家庭成员被确诊为精神分裂症，我们就会对所有家庭成员实施以下无创、风险最小的治疗方案。有三种神经生理和三种神经认知评估包括在这个电池中。神经生理学评估测量对各种听觉和视觉刺激的反应缺陷。这三种神经认知评估衡量的是眼球追踪、言语记忆和工作记忆的缺陷。我们还将收集每位参与家庭成员的血液样本，用于DNA提取和基因分析。我们的合作小组由七个地点的调查人员组成。在5年的时间里，联合站点将招募1680名DSM-IV精神分裂症患者和525名正常受试者。所有站点将从大型区域卫生保健系统和/或大型大都市医院招募受试者。具体措施中遗传缺陷的发现将用于指导精神分裂症遗传学的进一步研究。

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 seen in unaffected relatives of schizophrenics, which indicate 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.