Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia
Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia
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DOI：
10.1016/s0006-3223(00)01117-3
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发表时间：
2001-05-15
影响因子：
10.6
通讯作者：
Johnstone, EC
中科院分区：
文献类型：
--
作者：
Lawrie, SM;Whalley, HC;Johnstone, EC
背景资料：精神分裂症患者的大脑结构磁共振成像（MRI）一直显示出几种异常。这些被认为是神经发育的起源，因为它们也被描述在首次发作的情况下，虽然可能有一个渐进的组成部分。目前还不知道在发展中的这些异常是明显的，也不知道在何种程度上，他们是遗传或环境mediated.Methods：一百四十七个高风险的主题（至少有两个受影响的第一或第二度亲属），34例患者在他们的第一次发作，和36名健康对照组受试者接受了MRI扫描覆盖整个大脑。在不均匀性校正后，由三个组盲评分者追踪感兴趣的区域，具有良好的评分者间信度。区域脑容量相关的措施，精神分裂症的遗传倾向和精神病症状引起的结构化精神interventions.Results：高风险的主题有统计学意义上显着减少平均体积的左，右杏仁海马和丘脑，相比健康对照组。与精神分裂症患者相比，他们的双侧杏仁核和豆状核更大，双侧豆状核更小。有症状的高风险受试者的大脑比没有症状的人小。额前叶和丘脑的体积是唯一一致的协会的遗传liability.Conclusions：主题在发展精神分裂症的高风险有异常的大脑结构相似，但不相同的精神分裂症中发现的。我们的研究结果表明，一些结构异常是遗传性状或脆弱性标志物，其他是环境介导的，症状的发展与第三组重叠的结构变化有关。精神分裂症的特定风险因素可能在神经发育的离散时间点相互作用，对特定脑区产生不同影响，并可能代表相对不同的疾病过程。
Background: Structural magnetic resonance imaging (MRI) of the brain in patients with schizophrenia has consistently demonstrated several abnormalities. These are thought to be neurodevelopmental in origin, as they have also been described in first episode cases, although there may be a progressive component. It is not known at which point in development these abnormalities are evident, nor to what extent they are genetically or environmentally mediated.Methods: One hundred forty-seven high-risk subjects (with at least two affected first or second degree relatives), 34 patients in their first episode, and 36 healthy control subjects received an MRI scan covering the whole brain. After inhomogeneity correction, regions of interest were traced by three group-blind raters with good inter-rater reliability. Regional brain volumes were related to measures of genetic liability to schizophrenia and to psychotic symptoms elicited at structured psychiatric interviews.Results: High-risk subjects had statistically significantly reduced mean volumes of the left and right amygdalo-hippocampus and thalamus, as compared to healthy control subjects. They also had bilaterally larger amygdalo-hippocampi and bilaterally smaller lenticular nuclei than the schizophrenics. High-risk subjects with symptoms had smaller brains than those without. The volumes of the prefrontal lobes and the thalamus were the only consistent associates of genetic liability.Conclusions: Subjects at high risk of developing schizophrenia have abnormalities of brain structure similar to but not identical to those found in schizophrenia. Our results suggest that some structural abnormalities are genetic trait or vulnerability markers, others are environmentally mediated, and that the development of symptoms is associated with a third overlapping group of structural changes. Particular risk factors for schizophrenia may interact at discrete time points of neurodevelopment with different effects on specific brain regions and may represent relatively distinct disease processes.