Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders
Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders
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DOI：
10.1001/jamapsychiatry.2020.2694
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发表时间：
2021-01-01
期刊：
影响因子：
25.8
通讯作者：
Paus, Tomas
中科院分区：
文献类型：
--
作者：
Patel, Yash;Parker, Nadine;Paus, Tomas
重要性
大规模神经影像学研究揭示了许多精神疾病在皮质厚度方面的群体差异。这些差异背后的潜在神经生物学机制尚未得到很好的理解。
目的
确定6种疾病（注意缺陷/多动障碍（ADHD）、自闭症谱系障碍（ASD）、双相情感障碍（BD）、重度抑郁症（MDD）、强迫症（OCD）和精神分裂症）病例与对照之间皮质厚度群体差异的神经生物学相关性。
设计、环境和参与者
使用T1加权磁共振图像生成病例与对照之间皮质厚度群体差异的特征图谱。在每种疾病中研究细胞特异性基因表达的区域间特征图谱与皮质厚度群体差异特征图谱之间的相似性。接下来，使用主成分分析揭示这些疾病之间皮质厚度群体差异的共同特征图谱。对与这些疾病相关的基因进行共表达分析、聚类和富集分析。数据分析于2019年6月至12月进行。分析包括来自ENIGMA联盟的6种精神疾病的145个队列。6种疾病中每种疾病的病例数和对照数如下：ADHD：1814例和1602例；ASD：1748例和1770例；BD：1547例和3405例；MDD：2658例和3572例；OCD：2266例和2007例；精神分裂症：2688例和3244例。
主要结果和测量指标
病例与对照之间皮质厚度群体差异的区域间特征图谱。
结果
本研究共纳入12721例病例和15600例对照，年龄范围为2岁至89岁。6种精神疾病中每种疾病的皮质厚度群体差异的区域间特征图谱与锥体（CA1）细胞、星形胶质细胞（BD除外）和小胶质细胞（OCD除外）特异性基因表达特征图谱相关；这3种细胞类型的基因表达特征图谱共同解释了皮质厚度群体差异区域间特征图谱中25% - 54%的方差。主成分分析揭示了6种疾病之间皮质厚度差异的共同特征图谱（解释了48%的方差）；主成分1的区域间特征图谱与锥体细胞基因表达特征图谱相关（解释了区域间变异的56%）。对这些基因的共表达分析揭示了2个聚类：（1）一个富集参与神经发育（轴突导向）过程的基因的产前聚类和（2）一个富集参与突触活动和可塑性相关过程的基因的产后聚类。这些聚类富集了与所有6种精神疾病相关的基因。
结论和相关性
在本研究中，共享的神经生物学过程与多种精神疾病的皮质厚度差异相关。这些过程暗示了大脑皮质的产前发育和产后功能在这些疾病中的共同作用。
问题
各种精神疾病中皮质厚度群体差异的神经生物学基础是什么？
发现
在对来自145个队列的数据进行的联盟分析中，在所有6种疾病（注意缺陷/多动障碍、自闭症谱系障碍、双相情感障碍、重度抑郁症、强迫症和精神分裂症）中，锥体（CA1）细胞特异性基因表达较高的大脑皮质区域也是病例 - 对照组皮质厚度差异较大的区域。这些疾病之间存在皮质厚度群体差异的共同特征图谱，它与参与神经发育过程（产前）以及突触活动和可塑性基础过程（产后）的基因表达相关。
意义
多种精神疾病的皮质厚度差异存在共享的神经生物学和细胞机制，暗示了大脑皮质的产前发育和产后功能的共同作用。本研究评估了6种精神疾病病例与对照之间皮质厚度群体差异的神经生物学相关性。
Importance Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. Objective To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. Design, Setting, and Participants Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. Main Outcomes and Measures Interregional profiles of group difference in cortical thickness between cases and controls. Results A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. Conclusions and Relevance In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.Question What are the neurobiologic underpinnings of group differences in cortical thickness in various psychiatric disorders? Findings In this consortium analysis of data from 145 cohorts, regions of the cerebral cortex with greater expression of genes specific to pyramidal (CA1) cells were also regions with greater case-control group differences in cortical thickness in all 6 disorders: attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, and schizophrenia. There was a common profile of group differences in cortical thickness shared among these disorders, which was associated with the expression of genes involved in neurodevelopmental processes (prenatally) and processes underlying synaptic activity and plasticity (postnatally). Meaning There are shared neurobiologic and cellular mechanisms associated with differences in cortical thickness across multiple psychiatric disorders, implicating a common role of prenatal development and postnatal functioning of the cerebral cortex.This study evaluates neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 psychiatric disorders.