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与重度抑郁症发病机制相关的关键基因的鉴定与分析

Identification and Analyses of Crucial Genes Associated with Pathogenesis of Major Depressive Disorder.

作者信息

Li Jiao, Ma Qing, Ai Ming

机构信息

Department of the First Clinical Medicine, Chongqing Medical University, Chongqing, China.

Department of Pharmacy Practice, University at Buffalo, Buffalo, New York, USA.

出版信息

Psychiatry Clin Psychopharmacol. 2023 Dec 1;33(4):264-271. doi: 10.5152/pcp.2023.22488. eCollection 2023 Dec.

DOI:10.5152/pcp.2023.22488
PMID:38765844
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11037474/
Abstract

BACKGROUND

Major depressive disorder is a debilitating mental condition that causes severe disability leading to a high fatality rate. No valid blood-based biomarkers for major depressive disorder are currently available. The purpose of this research is to investigate gene biomarkers and pathways that may be linked to major depressive disorder pathogenesis.

METHODS

Two microarray databases were retrieved from Gene Expression Omnibus for screening of candidate differentially expressed genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed followed by protein-protein interaction network of differentially expressed genes.

RESULTS

About 1181 differentially expressed genes were identified from the microarray databases. Gene Ontology analyses indicated that these differentially expressed genes were significantly enriched in mRNA splicing via spliceosome, neutrophil degranulation, peptide antigen assembly with MHC class II protein complex, and immunoglobulin production-mediated immune response. The most enriched Kyoto Encyclopedia of Genes and Genomes pathway terms of the 10 significant were Hematopoietic cell lineage. About 20 genes were identified as hub genes after pathway analyses, mostly involved in colorectal cancer and the composition of ribosomes and protein processing, including KRAS, CD86, RPL9, RPL3, and RPL18.

CONCLUSION

New candidate genes have been identified using bioinformatic approaches that suggest their involvement in the pathogenesis of major depressive disorder and serve as potential genetic diagnostic markers as well as new therapeutic targets.

摘要

背景

重度抑郁症是一种使人衰弱的精神疾病,会导致严重残疾并致使高死亡率。目前尚无有效的基于血液的重度抑郁症生物标志物。本研究的目的是调查可能与重度抑郁症发病机制相关的基因生物标志物和信号通路。

方法

从基因表达综合数据库中检索两个微阵列数据库,以筛选候选差异表达基因。进行基因本体论和京都基因与基因组百科全书信号通路分析,随后构建差异表达基因的蛋白质-蛋白质相互作用网络。

结果

从微阵列数据库中鉴定出约1181个差异表达基因。基因本体论分析表明,这些差异表达基因在通过剪接体进行的mRNA剪接、中性粒细胞脱颗粒、肽抗原与MHC II类蛋白复合物组装以及免疫球蛋白产生介导的免疫反应中显著富集。10个显著的京都基因与基因组百科全书信号通路术语中最富集的是造血细胞谱系。通路分析后鉴定出约20个基因为枢纽基因,主要涉及结直肠癌以及核糖体组成和蛋白质加工,包括KRAS、CD86、RPL9、RPL3和RPL18。

结论

已使用生物信息学方法鉴定出新的候选基因,表明它们参与重度抑郁症的发病机制,并可作为潜在的基因诊断标志物以及新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/31876c6e5e02/pcp-33-4-264_f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/d8fd5d28b176/pcp-33-4-264_f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/13d0ee71a9d0/pcp-33-4-264_f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/3aef25217907/pcp-33-4-264_f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/d1b0b5362df4/pcp-33-4-264_f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/31876c6e5e02/pcp-33-4-264_f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/d8fd5d28b176/pcp-33-4-264_f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/13d0ee71a9d0/pcp-33-4-264_f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/3aef25217907/pcp-33-4-264_f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/d1b0b5362df4/pcp-33-4-264_f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c699/11037474/31876c6e5e02/pcp-33-4-264_f005.jpg

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本文引用的文献

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Immune signature of multiple sclerosis-associated depression.多发性硬化症相关抑郁症的免疫特征。
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Identification of Diagnostic Markers for Major Depressive Disorder Using Machine Learning Methods.
使用机器学习方法识别重度抑郁症的诊断标志物
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Orbitofrontal cortex grey matter volume is related to children's depressive symptoms.眶额皮质灰质体积与儿童的抑郁症状有关。
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Sex-dependent grades of haematopoietic modulation in patients with major depressive episodes are associated with suicide attempts.伴有自杀未遂的重度抑郁发作患者中造血调节的性别依赖性分级。
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