Our new findings link miR-151a-3p and miR-221/222 with SSRI sensitivity phenotypes in human cells via direct regulation of CHL1 and ITGB3. Importantly, we show that human miR-151a-3p and miR-221/222 and their respective target genes, CHL1 and ITGB3, may be implicated in the response of human LCLs to SSRI antidepressant drugs and may tentatively serve as novel MDD drug targets, following validation by additional studies using clinical blood samples and/or studies with brain tissues or blood samples from animal MDD models. This evidence concerns the gene ITGB3 and major depressive disorder.