To test this, we employed an integrative computational biology approach with the following aims: to investigate the potential causal effect of ACR on MDD risk using Mendelian randomization (MR); to identify the core protein targets and biological pathways through network toxicology and transcriptomic analysis; and to specifically test the novel hypothesis that SIRT3-mediated mitochondrial oxidative injury is a central mechanism linking ACR to depression, using molecular docking and dynamics simulations. This evidence concerns the gene SIRT3 and depressive disorder.