Plasma exosomal derived CCDC18AS1/miR-6835-5p/CCND2 axis sever as biomarkers for diagnosis and predicting therapeutic effect of Adolescent with MDD

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 and therapeutic biomarkers for adolescent with MDD remain unclear. Circulating exosomes could package nucleic acids from host cells and deliver them to recipient cells to play a vital role in intercellular communications, which are widely considered to be crucial for biomarker discovery for clinical diagnostics and therapy. Results In discovery set, we conducted microarray analysis to detect differential expression lncRNAs and mRNAs of plasma exosome and performed bioinformation analysis to construct lncRNAs-miRNAs-mRNAs networks from 10 adolescent MDD patients and 10 healthy controls, identifying 3752 differential expression lncRNAs and 1789 differential expression mRNAs and selecting AC156455.1/miR-126-5p/AAK1 and CCDC18AS1/miR-6835-5p/CCND2 axes from networks as candidate genes. In the validation set, 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 were differences in therapeutic effects. We also found that the expression of CCDC18AS1/miR-6835-5p/CCND2 axis at baseline could predicted sertraline therapeutic effects, which may be mediated through improving suicidal ideation and cognitive function. Conclusion Our study identified and validated the plasma exosme derived lncRNAs, miRNAs and mRNAs altered in adolescent with MDD, and provided potential diagnosis and therapeutic biomarkers for adolescent with MDD.