The pathogenesis of depression is associated with synaptic impairment and dysfunction in autophagy processes. Mendelian randomization (MR) analysis revealed that six GWAS IDs revealed a significant association between Beclin-1 levels and depression risk. Besides, all SNPs had a positive effect on depression risk. Analyzing neurons from depressed individuals using single-cell RNA sequencing (scRNA-seq) uncovered decreased expression of AKT, mTOR, and genes linked to synaptic plasticity. The activation of the PI3K/AKT/mTOR signaling has been demonstrated to control autophagy and have a protective effect on the nervous system. Hydrogen sulfide (H