The role of mitochondria in the pathophysiology of schizophrenia: A critical review of the evidence focusing on mitochondrial complex one.

There has been increasing interest in the role of mitochondrial dysfunction in the pathophysiology of schizophrenia. Mitochondrial complex one (MCI) dysfunction may represent a mechanism linking bioenergetic impairment with the alterations in dopamine signalling, glutamatergic dysfunction, and oxidative stress found in the disorder. New lines of evidence from novel approaches make it timely to review evidence for mitochondrial involvement in schizophrenia, with a specific focus on MCI. The most consistent findings in schizophrenia relative to controls are reductions in expression of MCI subunits in post-mortem brain tissue (Cohen's d> 0.8); reductions in MCI function in post-mortem brains (d> 0.7); and reductions in neural glucose utilisation (d= 0.3 to 0.6). Antipsychotics may affect glucose utilisation, and, at least in vitro, affect MC1. The findings overall are consistent with MCI dysfunction in schizophrenia, but also highlight the need for in vivo studies to determine the link between MCI dysfunction and symptoms in patients. If new imaging tools confirm MCI dysfunction in the disease, this could pave the way for new treatments targeting this enzyme.