Promotion of oligodendrogenesis and myelination can lead to functional benefits and regeneration to combat abnormal neurodevelopment and neurodegeneration of SMI. Modulation of stem cells and physiological Ca2±dependent/activated proteins will be tested in future pre-clinical models and translational studies. Wnt signaling may be critical regulators of these mechanisms in psychiatry and stem cell transplantation therapy for regeneration and repair. Intranasal delivery of hypoxic preconditioned stem cells may be the most appropriate method for psychotic disorders. Neuroimaging is useful in the pathophysiological study of SMI and the evaluation for treatments based on changes in neural activities and WM integrity. Higher-resolution precise imaging may further allow the development of stem cell treatment targeting specific brain regions.