Gur Raquel E, Nimgaonkar Vishwajit L, Almasy Laura, Calkins Monica E, Ragland J Daniel, Pogue-Geile Michael F, Kanes Stephen, Blangero John, Gur Ruben C
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Am J Psychiatry. 2007 May;164(5):813-9. doi: 10.1176/ajp.2007.164.5.813.
Genetic factors contribute to the development of schizophrenia where cognitive dysfunction is a hallmark. The purpose of this article was to examine computerized neurocognitive measures as candidate endophenotypic markers of liability for schizophrenia in a genetically informative cohort.
European Americans from 35 multiplex multigenerational families (N=349) and healthy participants (N=154) underwent clinical assessments and neurocognitive measurements and provided blood samples. The neurocognitive measures included performance (accuracy and speed) from a computerized battery that assessed abstraction/mental flexibility; attention; verbal, face, and spatial memory; spatial processing; sensorimotor processing; and emotion intensity discrimination.
Probands, relatives, and comparison subjects differed from each other in performance. Probands demonstrated greatest impairment relative to comparison subjects, followed by family members. Liability for schizophrenia affected the speed-accuracy tradeoff differently for specific neurocognitive domains. Significant heritability estimates were obtained for accuracy of verbal, facial, and spatial memory and spatial and emotion processing. For speed, estimates of heritability were significant for abstraction/mental flexibility, attention, face memory, and spatial and sensorimotor processing.
In a multigenerational multiplex design, the authors demonstrated that neurocognitive measures are associated with schizophrenia, differentiate unaffected relatives from comparison subjects, and may have significant presumed heritability. Therefore, they are endophenotypes suitable for genetic studies. Accuracy and speed can be differentially sensitive to presumed genetic liability.
遗传因素在精神分裂症的发病过程中起作用，认知功能障碍是其一个标志。本文旨在研究计算机化神经认知测量指标，作为具有遗传信息的队列中精神分裂症易感性的候选内表型标记。
来自35个多重多代家庭的欧裔美国人（N = 349）和健康参与者（N = 154）接受了临床评估和神经认知测量，并提供了血样。神经认知测量包括一个计算机化测试组的表现（准确性和速度），该测试组评估抽象/心理灵活性、注意力、言语、面部和空间记忆、空间处理、感觉运动处理以及情绪强度辨别。
先证者、亲属和对照受试者在表现上彼此不同。与对照受试者相比，先证者表现出最大程度的损害，其次是家庭成员。精神分裂症易感性对特定神经认知领域的速度 - 准确性权衡的影响不同。对于言语、面部和空间记忆以及空间和情绪处理的准确性，获得了显著的遗传力估计值。对于速度，抽象/心理灵活性、注意力、面部记忆以及空间和感觉运动处理的遗传力估计值显著。
在多代多重设计中，作者证明神经认知测量指标与精神分裂症相关，可区分未受影响的亲属与对照受试者，并且可能具有显著的假定遗传力。因此，它们是适合遗传研究的内表型。准确性和速度可能对假定的遗传易感性有不同的敏感性。
