Verma Pragya, Shakya Madhvi
Department of Bioinformatics, MANIT, Bhopal, Madhya Pradesh, India.
Indian J Psychiatry. 2021 Nov-Dec;63(6):549-553. doi: 10.4103/psychiatry.IndianJPsychiatry_858_20. Epub 2021 Dec 3.
Major depressive disorder (MDD) is a common psychiatric disorder characterized by constant sadness and a lack of interest in work and social interactions. Maintaining the transcriptome levels via the controlled regulation of mRNA processing and transport is essential to alleviating MDD. Various molecular phenotypes such as aberrant RNA splicing and stability are identified as critical determinants of MDD.
This study aims to compare the mRNA expression profiles between major depressive disorder non-suicide (MDD), major depressive disorder suicide (MDD-S), and control groups using RNA-Seq.
A transcriptomics and sequencing analysis of gene expression profiling was conducted in 9 patients with MDD, 10 patients with MDD-S, and 10 control patients.
A comparison of the sample groups revealed that the PRKACB gene was upregulated in patients with MDD. At the same time, GRM3, DLGAP1, and GRIA2 were downregulated in these patients-these genes are majorly involved in the glutamatergic pathway. Five genes (GRIA1, CAMK2D, PPP3CA, MAPK10, and PPP2R2A) of the dopaminergic pathway were downregulated in patients with the MDD-S condition when compared with the MDD and control groups. Cholinergic synapses were altered in patients with MDD when compared to the control group due to the presence of dysregulated genes (KCNQ5, PLCB4, ADCY9, CAMK2D, PIK3CA, and GNG2).
The results provide a new understanding of the etiology of depression in humans and identify probable depression-associated biomarkers.
重度抑郁症(MDD)是一种常见的精神疾病,其特征为持续的悲伤以及对工作和社交互动缺乏兴趣。通过对mRNA加工和转运的可控调节来维持转录组水平对于缓解MDD至关重要。各种分子表型,如异常的RNA剪接和稳定性,被确定为MDD的关键决定因素。
本研究旨在使用RNA测序比较重度抑郁症非自杀组(MDD)、重度抑郁症自杀组(MDD-S)和对照组之间的mRNA表达谱。
对9例MDD患者、10例MDD-S患者和10例对照患者进行了基因表达谱的转录组学和测序分析。
样本组比较显示,MDD患者中PRKACB基因上调。同时,这些患者中GRM3、DLGAP1和GRIA2基因下调,这些基因主要参与谷氨酸能通路。与MDD组和对照组相比,MDD-S患者中多巴胺能通路的五个基因(GRIA1、CAMK2D、PPP3CA、MAPK10和PPP2R2A)下调。与对照组相比,MDD患者由于存在失调基因(KCNQ5、PLCB4、ADCY9、CAMK2D、PIK3CA和GNG2),胆碱能突触发生改变。
这些结果为人类抑郁症的病因提供了新的认识,并确定了可能与抑郁症相关的生物标志物。