Asarnow Robert F, Nuechterlein Keith H, Subotnik Kenneth L, Fogelson David L, Torquato Richard D, Payne Diana L, Asamen Joy, Mintz Jim, Guthrie Donald
Neuropsychiatric Institute and the Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Room 48-240C NPI, 760 Westwood Plaza, Los Angeles, CA 90024-1759, USA.
Arch Gen Psychiatry. 2002 Nov;59(11):1053-60. doi: 10.1001/archpsyc.59.11.1053.
We tested the hypotheses that certain neurocognitive impairments index genetic liability to schizophrenia and that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining whether parents of COS probands show the types of neurocognitive impairments found in relatives of AOS probands.
Parents of COS probands (n = 79) were compared with parents of attention-deficit/hyperactivity disorder (ADHD; n = 190) and community control (CC; n = 115) probands on 3 neurocognitive tasks shown in previous research to detect impairments in patients with AOS and ADHD and in the relatives of patients with AOS. Parents with a diagnosis of psychosis were excluded from the study.
On the Degraded Stimulus-Continuous Performance Test and the Trail-Making Test B-Adolescent Version, the parents of COS probands performed significantly worse than the parents of CC and ADHD probands, who did not differ significantly from each other. On the Span of Apprehension, we found no significant group differences. Using rigorous cutoffs, a combination of scores on the 3 neurocognitive tests identified 16 (20%) of the mothers and fathers of COS probands compared with 0% of the mothers and fathers of CC probands. There was diagnostic specificity of the neurocognitive impairments. A combination of neurocognitive scores identified 6 (12%) of the mothers of COS probands vs 0% of the mothers of ADHD probands. A cutoff that identified 2 (2%) of the fathers of ADHD probands classified 5 (17%) of the fathers of COS probands. We found no significant differences in neurocognitive functions between the parents of ADHD and CC probands.
The aggregation of neurocognitive impairments in the parents of COS probands provides further evidence of etiologic continuity between COS and AOS. A substantial subgroup of parents of COS probands had a worse neurocognitive performance than that of any of the parents of ADHD and CC probands. Receiver operating characteristic curves showed that when rigorous cutoffs define neurocognitive impairments, the combination of scores on certain neurocognitive tasks produced a level of diagnostic accuracy in the parents of COS probands that is sufficient for use in genetic linkage studies.
我们通过确定儿童期起病精神分裂症（COS）先证者的父母是否表现出成人期起病精神分裂症（AOS）先证者亲属中发现的神经认知障碍类型，来检验某些神经认知障碍是否为精神分裂症的遗传易感性指标，以及儿童期起病精神分裂症是否为成人期起病精神分裂症的一种变体这两个假设。
将COS先证者的父母（n = 79）与注意力缺陷多动障碍（ADHD；n = 190）先证者的父母及社区对照（CC；n = 115）先证者的父母，就先前研究中显示可检测AOS患者、ADHD患者及其亲属中障碍的3项神经认知任务进行比较。患有精神病诊断的父母被排除在研究之外。
在退化刺激连续操作测试和青少年版连线测验B上，COS先证者的父母表现显著差于CC和ADHD先证者的父母，而后两者之间无显著差异。在领悟广度测试中，我们未发现显著的组间差异。使用严格的临界值，3项神经认知测试的分数组合在COS先证者的父母中识别出16名（20%）母亲和父亲，而CC先证者的父母中这一比例为0%。神经认知障碍具有诊断特异性。神经认知分数组合在COS先证者的母亲中识别出6名（12%），而ADHD先证者的母亲中这一比例为0%。一个能识别出2名（2%）ADHD先证者父亲的临界值，将5名（17%）COS先证者的父亲归为同一类别。我们发现ADHD和CC先证者的父母在神经认知功能上无显著差异。
COS先证者父母中神经认知障碍的聚集为COS和AOS之间的病因连续性提供了进一步证据。COS先证者父母中的一个相当大的亚组的神经认知表现比ADHD和CC先证者的任何一方父母都差。受试者工作特征曲线表明，当严格的临界值定义神经认知障碍时，某些神经认知任务的分数组合在COS先证者的父母中产生了足以用于遗传连锁研究的诊断准确性水平。
