AKT1 and major depressive disorder: In this regard, for example, there is evidence that confirms the antidepressant potential of ECM remodeling after chronic stress by mean of intra-cortical degradation of perineuronal nets (PNNs) [71]; or the role of the PI3K-Akt signaling pathway in proinflammatory regulatory mechanisms, given that neuron inflammation and inflammatory cytokine production contribute to the pathology of depression [72]; as well as, the alteration of circadian rhythms and disturbances of sleep [69, 73].