The antidepressants venlafaxine, a serotonin/norepinephrine reuptake inhibitor, has been shown to increase MMP-9 expression in the rodent brain and reduce PNN composition (Alaiyed et al., 2019), and subjects with MDD with antidepressant treatment have increased MMP-9 expression in the dorsolateral prefrontal cortex compared to control subjects (Alaiyed et al., 2020). This evidence concerns the gene MMP9 and major depressive disorder.