Xu Yifan, Zhang Rong, Du Xinzhe, Huang Yangxi, Gao Yao, Wen Yujiao, Qiao Dan, Sun Ning, Liu Zhifen
Department of Psychiatry, First Hospital /First Clinical Medical College of Shanxi Medical University, Taiyuan, China; Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China.
Department of Psychiatry, First Hospital /First Clinical Medical College of Shanxi Medical University, Taiyuan, China; Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China..
Genomics. 2025 Mar;117(2):110993. doi: 10.1016/j.ygeno.2025.110993. Epub 2025 Jan 9.
Major depressive disorder (MDD) during adolescence significantly jeopardizes both mental and physical health. However, the etiology underlying MDD in adolescents remains unclear.
A total of 74 adolescents with MDD and 40 health controls (HCs) who underwent comprehensive clinical and cognitive assessments were enrolled. Differential expression analysis was conducted on plasma extracellular vesicles (EVs) carrying long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) by microarray analysis. Two possible lncRNA-miR-mRNA networks were established and candidate regulatory axes were generated using the StarBase, miRDB, and TargetScan bioinformatics databases. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the candidate molecules and signaling axes in a clinical cohort.
A total of 3752 dysregulated lncRNAs and 1789 dysfunctional mRNAs were identified. Two candidate regulatory axes (AC156455.1/miR-126-5p/AAK1 and CCDC18-AS1/miR-6835-5p/CCND2) with potential connections with MDD were selected. The candidate molecules exhibit differential expression patterns among adolescents with MDD and HCs, as well as before and after treatment with sertraline in adolescents with MDD. Furthermore, AAK1, CCDC18-AS1, and miR-6835-5p expressions exhibited significant differences between the response and non-response groups. Baseline expression of CCDC18-AS1, miR-6835-5p, and CCND2 could predict the therapeutic effect of sertraline, which may be associated with reducing suicidal ideation and improving cognitive function.
Our study may provide insights into the understanding of the underlying pathological mechanisms in adolescents with MDD.
青少年期的重度抑郁症（MDD）严重危害身心健康。然而，青少年MDD的病因仍不清楚。
共纳入74例患有MDD的青少年和40例健康对照（HCs），他们均接受了全面的临床和认知评估。通过微阵列分析对携带长链非编码RNA（lncRNAs）和信使RNA（mRNAs）的血浆细胞外囊泡（EVs）进行差异表达分析。利用StarBase、miRDB和TargetScan生物信息学数据库建立了两个可能的lncRNA-miR-mRNA网络并生成候选调控轴。采用定量实时聚合酶链反应（qRT-PCR）在临床队列中验证候选分子和信号轴。
共鉴定出3752个失调的lncRNAs和1789个功能异常的mRNAs。选择了两个与MDD可能相关的候选调控轴（AC156455.1/miR-126-5p/AAK1和CCDC18-AS1/miR-6835-5p/CCND2）。候选分子在患有MDD的青少年和HCs之间以及患有MDD的青少年接受舍曲林治疗前后表现出不同的表达模式。此外，AAK1、CCDC18-AS1和miR-6835-5p的表达在反应组和无反应组之间存在显著差异。CCDC18-AS1、miR-6835-5p和CCND2的基线表达可以预测舍曲林的治疗效果，这可能与减少自杀意念和改善认知功能有关。
我们的研究可能为理解青少年MDD的潜在病理机制提供见解。
