Serum extracellular vesicle microRNA dysregulation and childhood trauma in adolescents with major depressive disorder

作者全名："Ran, Liu-Yi; Kong, Yi-Ting; Xiang, Jiao-Jiao; Zeng, Qi; Zhang, Chen-Yu; Shi, Lei; Qiu, Hai-Tang; Liu, Chuan; Wu, Lin-Li; Li, Ya-Lan; Chen, Jian-Mei; Ai, Ming; Wang, Wo; Kuang, Li"

作者地址："[Ran, Liu-Yi; Zeng, Qi; Liu, Chuan; Wu, Lin-Li; Li, Ya-Lan; Wang, Wo; Kuang, Li] Chongqing Med Univ, Mental Hlth Ctr, Univ Town Hosp, Chongqing, Peoples R China; [Kong, Yi-Ting; Xiang, Jiao-Jiao; Zhang, Chen-Yu; Shi, Lei; Qiu, Hai-Tang; Chen, Jian-Mei; Ai, Ming; Kuang, Li] Chongqing Med Univ, Affiliated Hosp 1, Dept Psychiat, Chongqing, Peoples R China"

通信作者："Kuang, L (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Psychiat, Chongqing 400016, Peoples R China.; Wang, W (通讯作者)，Chongqing Med Univ, Mental Hlth Ctr, Univ Town Hosp, Chongqing 401331, Peoples R China."

来源：BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000876948700003

JCR分区：Q3

影响因子：3.4

年份：2022

卷号：22

期号：6

开始页：959

结束页：971

文献类型：Article

关键词：Extracellular vesicle; miRNA; childhood trauma; major depressive disorder; adolescent

摘要："Major depressive disorder (MDD) seriously endangers adolescent mental and physical health. Extracellular vesicles (EVs) are mediators of cellular communication and are involved in many physiological brain processes. Although EV miRNAs have been implicated in adults with major psychiatric disorders, investigation into their effects in adolescent MDD remains scarce. In discovery set, we conducted a genome-wide miRNA sequencing of serum EVs from 9 untreated adolescents with MDD and 8 matched healthy controls (HCs), identifying 32 differentially expressed miRNAs (18 upregulated and 14 downregulated). In the validation set, 8 differentially expressed and highly enriched miRNAs were verified in independent samples using reverse-transcription polymerase chain reaction (RT-PCR), with 4 (miR-450a-2-3p, miR-3691-5p, miR-556-3p, and miR-2115-3p) of the 8 miRNAs found to be significantly elevated in 34 untreated adolescents with MDD compared with 38 HCs and consistent with the sequencing results. After the Bonferroni correction, we found that three miRNAs (miR-450a-2-3p, miR-556-3p, and miR-2115-3p) were still significantly different. Among them, miR-450a-2-3p showed the most marked differential expression and was able to diagnose disease with 67.6% sensitivity and 84.2% specificity. Furthermore, miR-450a-2-3p partially mediated the associations between total childhood trauma, emotional abuse, and physical neglect and adolescent MDD. We also found that the combination of miR-450a-2-3p and emotional abuse could effectively diagnose MDD in adolescents with 82.4% sensitivity and 81.6% specificity. Our data demonstrate the association of serum EV miRNA dysregulation with MDD pathophysiology and, furthermore, show that miRNAs may mediate the relationship between early stress and MDD susceptibility. We also provide a valid integrated model for the diagnosis of adolescent MDD."

基金机构："National Natural Science Foundation of China [82101615, 81971286, 81901373]; Natural Science Foundation of Chongqing, China [cstc2021jcyj-msxmX0349]; Science and Health Joint Medical Research Project Fund of Chongqing [2022QNXM001]"

基金资助正文："The National Natural Science Foundation of China (Grant NO. 82101615, 81971286, 81901373). The Natural Science Foundation of Chongqing, China (Grant NO. cstc2021jcyj-msxmX0349). The Science and Health Joint Medical Research Project Fund of Chongqing (Grant NO. 2022QNXM001)."