Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia
Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia
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DOI：
10.1073/pnas.052023499
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发表时间：
2002-03-05
影响因子：
11.1
通讯作者：
Kaprio, J
中科院分区：
文献类型：
--
作者：
Cannon, TD;Thompson, PM;Kaprio, J
精神分裂症的症状意味着支持高阶认知活动的大脑系统受到破坏，但这些系统是否在弥漫性皮质灰质缺陷的背景下受到不同的影响仍然不明确。精神分裂症患者的一些未受影响的一级亲属也表现出皮质灰质缺陷，但尚不清楚这些变化是否与患者的同构，并且答案对于理解给定易感基因型的疾病表达所需的神经生物学条件至关重要。在这里，我们报告了慢性精神分裂症不一致的同卵（MZ）和异卵（DZ）双胞胎以及人口统计学匹配的对照双胞胎的三维皮质表面图（在整个皮质中逐点匹配受试者解剖结构的概率图谱）。一张编码精神分裂症患者与其未受影响的同卵双胞胎之间平均差异的图谱显示，缺陷主要存在于背外侧前额叶皮层、颞上回和顶上小叶。与患者遗传接近度相关的编码变异图谱（同卵双胞胎>异卵双胞胎>对照双胞胎）主要在极区和背外侧前额皮质中分离出缺陷。在每种情况下，通过对 10,000 个蒙特卡洛排列的分析确认了统计显着性，并且对比分析显示其余皮层受到的影响显着较小。与疾病相关的灰质缺陷与症状严重程度和认知功能障碍相关，但与疾病持续时间或抗精神病药物治疗无关。因此，遗传和疾病特异性的影响会影响主要异模联结皮层部分不重叠区域的灰质，这些变化可能在产生该疾病的明显行为特征方面发挥协同作用。
The symptoms of schizophrenia imply disruption to brain systems supporting higher-order cognitive activity, but whether these systems are impacted differentially against a background of diffuse cortical gray-matter deficit remains ambiguous. Some unaffected first-degree relatives of schizophrenics also manifest cortical gray-matter deficits, but it is unclear whether these changes are isomorphic with those in patients, and the answer is critical to understanding the neurobiological conditions necessary for disease expression given a predisposing genotype. Here we report three-dimensional cortical surface maps (probabilistic atlases matching subjects' anatomy point by point throughout cortex) in monozygotic (MZ) and dizygotic (DZ) twins discordant for chronic schizophrenia along with demographically matched control twins. A map encoding the average differences between schizophrenia patients and their unaffected MZ co-twins revealed deficits primarily in dorsolateral prefrontal cortex, superior temporal gyrus, and superior parletal lobule. A map encoding variation associated with genetic proximity to a patient (MZ co-twins > DZ co-twins > control twins) isolated deficits primarily in polar and dorsolateral prefrontal cortex. In each case, the statistical significance was confirmed through analysis of 10,000 Monte Carlo permutations, and the remaining cortex was shown to be significantly less affected by contrast analysis. The disease-related deficits in gray matter were correlated with measures of symptom severity and cognitive dysfunction but not with duration of illness or antipsychotic drug treatment. Genetic and disease-specific influences thus affect gray matter in partially nonoverlapping areas of predominantly heteromodal association cortex, changes that may act synergistically in producing overt behavioral features of the disorder.