The interplay of dopamine metabolism abnormalities and mitochondrial defects in the pathogenesis of schizophrenia

Dopamine (DA) is a major monoamine neurotransmitter in the brain and has essential roles in higher functions of the brain. Malfunctions of dopaminergic signaling have been implicated in various mental disorders such as addiction, attention deficit/hyperactivity disorder, Huntington's disease, Parkinson's disease (PD), and schizophrenia. The pathogenesis of PD and schizophrenia involves the interplay of mitochondrial defect and DA metabolism abnormalities. This article focuses on this issue in schizophrenia. It started with the introduction of metabolism, behavioral action, and physiology of DA, followed by reviewing evidence for malfunctions of dopaminergic signaling in patients with schizophrenia. Then it provided an overview of multiple facets of mitochondrial physiology before summarizing mitochondrial defects reported in clinical studies with schizophrenia patients. Finally, it discussed the interplay between DA metabolism abnormalities and mitochondrial defects and outlined some clinical studies showing effects of combination therapy of antipsychotics and antioxidants in treating patients with schizophrenia. The update and integration of these lines of information may advance our understanding of the etiology, pathogenesis, phenomenology, and treatment of schizophrenia.