Aberrant plasma exosomal derived ceRNA networks as diagnosis biomarkers for adolescent major depressive disorder and its potential prediction for antidepressant

Abstract

Background: Major depressive disorder (MDD) in adolescence seriously endangers their mental and physical health and is associated with poor social and scholastic function. However, the diagnosis biomarkers for adolescent with MDD remain unclear. Methods：A total of 114 adolescent subjects were enrolled in this study, the comprehensive clinical and cognitive assessments were performed. Differential expressions of lncRNAs and mRNAs of plasma exosomes were screened by microarray assay. Two sets of ceRNA (lncRNAs-miRNAs-mRNAs) networks had been generated and candidate genes had been screened by bioinformatic analysis, and candidate genes were validated in cohort using qRT-PCR. Results：A total of 3752 differentially expressed lncRNAs and 1789 differentially expressed mRNAs were identified. AC156455.1, miR-126-5p, AAK1 and CCDC18AS1, miR-6835-5p, CCND2 were picked from each network as candidate genes. We found that the six candidate genes were differential expression between MDD patients and healthy controls, or before and after antidepressant treatment of MDD group. The expression levels of AAK1, CCDC18AS1 and miR6835 varied in efficacy after 8-week sertraline treatment. We also found that the expression of CCDC18AS1, miR-6835-5p, CCND2 (in the same network) at baseline could predicted antidepressant efficacy, which may be mediated through reducing suicidal ideation and improving cognitive function. Conclusion:Our study identified and validated the plasma exosome-derived ceRNA networks altered in adolescent with MDD, our findings provided potential diagnosis and therapeutic biomarkers for adolescent with MDD.