ICU, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, P.R. China.
Organ Transplant Center, Tianjin First Central Hospital, Tianjin, P.R. China.
Mol Genet Genomic Med. 2019 Jun;7(6):e659. doi: 10.1002/mgg3.659. Epub 2019 Apr 9.
Major depressive disorder (MDD) is a serious mental health problem in modern society, which is difficult to identify and diagnose in the early stages. Despite strong evidence supporting the heritability of MDD, progresses in large-scale and individual genetic studies remain preliminary.
In this study, a multi-data source-based prioritization (MDSP) method was proposed, and an appropriate threshold was determined for the optimization of depression-related genes (DEPgenes). Analyses on Gene Ontology biological processes, KEGG pathway and the specific pathway crosstalk network were further proposed.
A total of 143 DEPgenes were identified and the MDD-specific network was constructed for the pathogenesis investigation and therapeutic methods development of MDD. Comparing with existing research strategies, the genetic optimization and analysis results were confirmed to be reliable. Finally, the pathway enrichment and crosstalk analyses revealed two unique pathway interaction modules that were significantly enriched with MDD genes. The related core pathways of neuroactive ligand-receptor interaction and dopaminergic synapse supported the neuropathology hypothesis of MDD. And the pathways of serotonergic synapse and morphine addiction indicated the mechanism of drug addiction caused by serotonin used in the treatment.
This work provided a reference for the study of MDD, although future validation by extensive experimentation is still required.
重度抑郁症（MDD）是现代社会中一个严重的心理健康问题，在早期阶段难以识别和诊断。尽管有大量证据支持 MDD 的遗传性，但大规模和个体遗传学研究的进展仍处于初步阶段。
本研究提出了一种基于多数据源的优先级排序（MDSP）方法，并确定了适当的阈值，以优化与抑郁相关的基因（DEPgenes）。进一步提出了基因本体论生物过程、KEGG 途径和特定途径串扰网络的分析。
共鉴定出 143 个 DEPgenes，并构建了 MDD 特定网络，以研究 MDD 的发病机制和开发治疗方法。与现有研究策略相比，遗传优化和分析结果被证实是可靠的。最后，通路富集和串扰分析揭示了两个独特的通路相互作用模块，这些模块与 MDD 基因显著富集。与神经活性配体-受体相互作用和多巴胺能突触相关的核心通路支持 MDD 的神经病理学假说。而 5-羟色胺能突触和吗啡成瘾的通路则表明了治疗中使用的 5-羟色胺引起药物成瘾的机制。
尽管仍需要广泛的实验验证，但这项工作为 MDD 的研究提供了参考。
