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强迫症成年患者皮质厚度改变的遗传和分子关联:转录-神经影像学关联分析

Genetic and molecular correlates of cortical thickness alterations in adults with obsessive-compulsive disorder: a transcription-neuroimaging association analysis.

作者信息

Zhang Da, Teng Changjun, Xu Yinhao, Tian Lei, Cao Ping, Wang Xiao, Li Zonghong, Guan Chengbin, Hu Xiao

机构信息

Department of Radiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Department of Medical Psychology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Psychol Med. 2024 Oct 4;54(12):1-10. doi: 10.1017/S0033291724001909.

Abstract

BACKGROUND

Although numerous neuroimaging studies have depicted neural alterations in individuals with obsessive-compulsive disorder (OCD), a psychiatric disorder characterized by intrusive cognitions and repetitive behaviors, the molecular mechanisms connecting brain structural changes and gene expression remain poorly understood.

METHODS

This study combined the Allen Human Brain Atlas dataset with neuroimaging data from the Meta-Analysis (ENIGMA) consortium and independent cohorts. Later, partial least squares regression and enrichment analysis were performed to probe the correlation between transcription and cortical thickness variation among adults with OCD.

RESULTS

The cortical map of case-control differences in cortical thickness was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms preferentially expressed across different cell types and cortical layers. These genes were specifically expressed in brain tissue, spanning all cortical developmental stages. Protein-protein interaction analysis revealed that these genes coded a network of proteins encompassing various highly interactive hubs.

CONCLUSIONS

The study findings bridge the gap between neural structure and transcriptome data in OCD, fostering an integrative understanding of the potential biological mechanisms.

摘要

背景

尽管众多神经影像学研究已经描绘了患有强迫症(OCD)个体的神经改变,强迫症是一种以侵入性认知和重复行为为特征的精神疾病,但连接大脑结构变化与基因表达的分子机制仍知之甚少。

方法

本研究将艾伦人类大脑图谱数据集与来自荟萃分析(ENIGMA)联盟和独立队列的神经影像学数据相结合。随后,进行偏最小二乘回归和富集分析,以探究强迫症成年患者转录与皮质厚度变化之间的相关性。

结果

病例对照在皮质厚度上的差异皮质图谱在空间上与一组基因的皮质表达相关,这些基因是通过对在不同细胞类型和皮质层中优先表达的、富含神经生物学相关本体术语的加权组合。这些基因在脑组织中特异性表达,跨越所有皮质发育阶段。蛋白质-蛋白质相互作用分析表明,这些基因编码了一个包含各种高度相互作用中心的蛋白质网络。

结论

该研究结果填补了强迫症神经结构与转录组数据之间的空白,促进了对潜在生物学机制的综合理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae9/11496223/0ad2f686c81c/S0033291724001909_fig1.jpg

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