McDonald Colm, Bullmore Edward T, Sham Pak C, Chitnis Xavier, Wickham Harvey, Bramon Elvira, Murray Robin M
Division of Psychological Medicine, Institute of Psychiatry, London.
Arch Gen Psychiatry. 2004 Oct;61(10):974-84. doi: 10.1001/archpsyc.61.10.974.
For more than a century, it has been uncertain whether or not the major diagnostic categories of psychosis--schizophrenia and bipolar disorder--are distinct disease entities with specific genetic causes and neuroanatomical substrates.
To investigate the relationship between genetic risk and structural variation throughout the entire brain in patients and their unaffected relatives sampled from multiply affected families with schizophrenia or bipolar disorder.
Analysis of the association between genetic risk and variation in tissue volume on magnetic resonance images.
Psychiatric research center.
Subjects comprised 25 patients with schizophrenia, 36 of their unaffected first-degree relatives, 37 patients with bipolar 1 disorder who experienced psychotic symptoms during illness exacerbation, and 50 of their unaffected first-degree relatives.
We used computational morphometric techniques to map significant associations between a continuous measure of genetic liability for each subject and variation in gray or white matter volume.
Genetic risk for schizophrenia was specifically associated with distributed gray matter volume deficits in the bilateral fronto-striato-thalamic and left lateral temporal regions, whereas genetic risk for bipolar disorder was specifically associated with gray matter deficits only in the right anterior cingulate gyrus and ventral striatum. A generic association between genetic risk for both disorders and white matter volume reduction in the left frontal and temporoparietal regions was consistent with left frontotemporal disconnectivity as a genetically controlled brain structural abnormality common to both psychotic disorders.
Genetic risks for schizophrenia and bipolar disorder are associated with specific gray matter but generic white matter endophenotypes. Thus, Emil Kraepelin's pivotal distinction was neither wholly right nor wholly wrong: the 2 major psychoses show both distinctive and similar patterns of brain structural abnormality related to variable genetic risk.
一个多世纪以来，精神分裂症和双相情感障碍这两种主要的精神病诊断类别是否为具有特定遗传病因和神经解剖学基础的不同疾病实体一直不确定。
研究从多个患有精神分裂症或双相情感障碍的家庭中抽取的患者及其未患病亲属的遗传风险与全脑结构变异之间的关系。
分析遗传风险与磁共振图像上组织体积变异之间的关联。
精神病学研究中心。
受试者包括25名精神分裂症患者、36名其未患病的一级亲属、37名在疾病发作时出现精神病症状的双相I型障碍患者以及50名其未患病的一级亲属。
我们使用计算形态计量学技术来绘制每个受试者的遗传易感性连续测量值与灰质或白质体积变异之间的显著关联。
精神分裂症的遗传风险与双侧额纹状体丘脑和左侧颞叶区域的分布式灰质体积缺陷特别相关，而双相情感障碍的遗传风险仅与右侧前扣带回和腹侧纹状体的灰质缺陷特别相关。两种疾病的遗传风险与左侧额叶和颞顶叶区域白质体积减少之间的一般关联与左额颞叶连接中断一致，这是两种精神病共有的一种由基因控制的脑结构异常。
精神分裂症和双相情感障碍的遗传风险与特定的灰质但一般的白质内表型相关。因此，埃米尔·克雷佩林的关键区分既不完全正确也不完全错误：这两种主要的精神病表现出与可变遗传风险相关的独特和相似的脑结构异常模式。
