Proposed pathophysiology of schizophrenia. Mitochondrial dysfunction (MD), through imbalance of ROS production and removal, raises ROS emission, causing a strong intracellular OS. Disturbed OXPHOS and enhanced OS in predisposed individuals may cause various pathogenic alterations such as genomic instability, aberrations in neuromuscular development, brain dysfunction, and apoptosis. On the other hand, enhanced OS and secondarily induced alteration of redox coenzyme homeostasis may cause enhanced CS. It is assumed that the brain has the third class of antioxidant defenses in which neurotransmissions are involved, and that trans-synaptic activation of NMDA-R as well as DA-R may occur, through unknown pre-synaptic redox regulation mechanisms, as an adaptive response to OS which could not be suppressed by the class I (non-enzymatic) and II (enzymatic) defenses. Failure to suppress OS by those three classes of antioxidant defenses may lead to persistent strong OS and, through suppressing the expression of inhibitory interneurons, may cause prolonged excessive glutamate and/or DA release, leading to excitation toxicity (ET) and additional deterioration of the brain function.