Plasma Exosomal Derived CCDC18AS1/miR-6835-5p/CCND2 Axis Sever as Biomarkers for Diagnosis and Predicting Efficacy of Adolescent with Major Depressive Disorder

Abstract 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 and therapeutic biomarkers for adolescent with MDD remain unclear. Differential expressions of lncRNAs and mRNAs of plasma exosome were screened from 10 adolescent MDD patients and 10 healthy controls by microarray, lncRNAs-miRNAs-mRNAs networks had been generated by bioinformatic analysis, especially, 3752 differential expressions of lncRNAs and 1789 differential expression of mRNAs were included. 2 sets of axes such as AC156455.1/miR-126-5p/AAK1 and CCDC18AS1/miR-6835-5p/CCND2 were picked from networks. Candidate lncRNAs, miRNAs and mRNAs were verified in 64 adolescent MDD patients (MDD group) and 30 healthy controls (HC group) using qRT-PCR. We found that six candidate genes were differential expression between MDD group and HC group, 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 axis at baseline could predicted sertraline efficacy, which may be mediated through reducing suicidal ideation and improving cognitive function. Our study identified and validated the plasma exosome- derived lncRNAs, miRNAs and mRNAs altered in adolescent with MDD, our findings provided potential diagnosis and therapeutic biomarkers for adolescent with MDD.