Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a multisite mega-analysis of 983 patients and 1349 healthy controls
Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a multisite mega-analysis of 983 patients and 1349 healthy controls
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DOI：
10.1038/mp.2017.106
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发表时间：
2018-06-01
影响因子：
11
通讯作者：
Westlye, L. T.
中科院分区：
文献类型：
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作者：
Moberget, T.;Doan, N. T.;Westlye, L. T.
虽然小脑参与广泛的认知和神经精神表型越来越被认可，以前的大规模研究精神分裂症（SZ）主要集中在幕上结构。因此，SZ中小脑相对于大脑形态学差异的跨样本重现性、区域分布、与大脑皮层形态学的相关性和效应量尚不清楚。我们在来自14个国际样本的983名SZ谱系障碍患者和1349名健康对照（HC）中解决了这些问题，使用针对小脑和大脑优化的最先进的图像分析管道。结果显示，相对于HC，SZ中的小脑灰质总体积显著减少（Cohens d = -0.35），其中在小脑区域中的作用最强，显示出与额顶叶皮质的功能连接（d = -0.40）。小脑体积的效应量与SZ中最一致报告的大脑结构变化相似（例如，海马体积和额颞皮质厚度），并且在样品之间高度一致。在组内，我们进一步观察到小脑体积与额颞区大脑皮质厚度之间的正相关性（即，与同样显示SZ减少的区域重叠）。这种小脑结构的协方差性在SZ中最强，表明共同影响小脑和大脑的常见潜在疾病过程。最后，SZ的小脑体积减小在所包括的年龄跨度（16-66岁）中高度一致，并且在最年轻的患者中已经存在，这一发现与神经发育而不是神经退行性病因更一致。总之，这些新的发现建立小脑作为一个关键节点的分布式大脑网络的基础SZ。
Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum. Results showed that total cerebellar grey matter volume was robustly reduced in SZ relative to HCs (Cohens's d = -0.35), with the strongest effects in cerebellar regions showing functional connectivity with frontoparietal cortices (d = -0.40). Effect sizes for cerebellar volumes were similar to the most consistently reported cerebral structural changes in SZ (e.g., hippocampus volume and frontotemporal cortical thickness), and were highly consistent across samples. Within groups, we further observed positive correlations between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in SZ). This cerebellocerebral structural covariance was strongest in SZ, suggesting common underlying disease processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar volume reduction in SZ was highly consistent across the included age span (16-66 years) and present already in the youngest patients, a finding that is more consistent with neurodevelopmental than neurodegenerative etiology. Taken together, these novel findings establish the cerebellum as a key node in the distributed brain networks underlying SZ.