Hypothetical changes in PNN deposition and MMP-9 activity in untreated and treated MDD. Hypothetical PNN, MMP levels, and E/I balance (arbitrary units) are shown for nondepressed control patients. With MDD, PNN levels increase and thus E/I balance decreases. With MDD in the setting of antidepressant therapy, however, MMP levels also increase to potentially restore E/I balance.