Clinical and genetic high-risk strategies in understanding vulnerability to psychosis
Clinical and genetic high-risk strategies in understanding vulnerability to psychosis
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DOI：
10.1016/j.schres.2005.06.014
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发表时间：
2005-11-01
影响因子：
4.5
通讯作者：
Cannon, TD
中科院分区：
文献类型：
--
作者：
Cannon, TD
在青少年时期活跃的神经发育过程被假设参与与精神分裂症发病相关的功能恶化。目前有许多研究正在对处于超高风险临床状态的个体进行反复的神经影像学评估，以确定特定的神经变化是否预示着即将发作的精神病。然而，如果不参考对这些神经指标在精神分裂症患者有临床行为影响的一级亲属中分布的研究，这些研究的结果将难以解释。最近主要来自双胞胎和家族研究（即遗传高风险设计）的工作表明，精神分裂症患者脑功能和结构的一些改变主要是遗传介导的，也出现在一些未受影响的一级亲属中，而其他改变存在于表现出疾病表型的个体中，但不存在于具有遗传风险的亲属中。然而，主要由基因介导的缺陷在有风险但无症状的亲属中不太可能在发病前表现出差异变化，并且可能是必要的，但显然不是精神病症状发展的充分条件，表现出疾病表型的患者特有的缺陷是标记与精神分裂症发病时精神病症状出现相关的神经生物学过程的良好候点。纵向研究的初步结果最初确定在前驱（即“临床高风险”）状态的个体似乎可以在这个框架内解释。(c) 2005 Elsevier B.V.版权所有
Neurodevelopmental processes active during the adolescent period have been hypothesized to participate in the deterioration in functioning associated with the onset of schizophrenia. A number of studies are now underway evaluating individuals in an ultra high-risk clinical state with neuroimaging assessments repeatedly over time, to determine whether particular neural changes predict an imminent onset of psychosis. However, the results of such studies will be difficult to interpret without reference to studies examining the distribution of these neural indicators in the tion-clinically-affected first-degree relatives of patients with schizophrenia. Recent work deriving primarily from twin and farnily studies (i.e., genetic high-risk designs) indicates that some of the alterations in brain function and structure in schizophrenia are primarily genetically mediated and also appear in some of their unaffected first-degree relatives, while other alterations are present in individuals who manifest the illness phenotype but not in relatives at genetic risk. Whereas the primarily genetically mediated deficits shared by at-risk but non-symptomatic relatives are not likely to show differential change in the premorbid period, and may be necessary but clearly not sufficient for the development of psychotic symptoms, the deficits specific to patients who manifest the illness phenotype are good candidates for marking the neurobiological processes associated with the emergence of psychotic symptoms at the time of schizophrenia onset. Preliminary results from longitudinal studies of individuals ascertained initially in a prodrornal (i.e., "clinical high-risk") state appear to be interpretable within this framework. (c) 2005 Elsevier B.V. All rights reserved.