Identification of Aberrant Plasma Exosomal Derived ceRNA Networks in Adolescent with Major Depressive Disorder

Abstract Major Depressive Disorder (MDD) during adolescence significantly jeopardizes both mental and physical well-being. However, the etiology underlying MDD in adolescents remains unclear. Our study enrolled a total of 114 adolescent participants who underwent comprehensive clinical and cognitive assessments. Differential expressions of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) within plasma exosomes were determined through microarray analysis. A total of 3752 dysregulated lncRNAs and 1789 dysregulated mRNAs were identified. Subsequently, two distinct sets of competitive endogenous RNA (ceRNA) networks were established. The candidate regulatory axes (AC156455.1/miR126-5p/AAK1 and CCDC18AS1/miR6835-5p/CCND2) were chosen from the ceRNA networks and subsequently validated within the cohort using quantitative real-time polymerase chain reaction (qRT-PCR). Our findings reveal that the candidate regulatory axes exhibit diverse expression patterns among both adolescents with MDD and healthy controls (HCs), both prior to and post-treatment in adolescents with MDD. Furthermore, the expression levels of AAK1, CCDC18AS1, and miR6835-5p exhibited significant differences between the response and non-response groups. Baseline expression level of CCDC18-AS1, miR-6835-5p and CCND2 could predict the therapeutic effect of sertraline, which may be achieved by reducing suicidal ideation and improving cognitive function. Our results may provide prospective insights into the underlying pathological mechanisms in adolescents with MDD.