BACKGROUND: Mitochondria have been suggested to be involved in the pathology of 
bipolar disorder (BD) and schizophrenia. However, the mechanism underlying 
mitochondrial dysfunction is unclear. Mitochondrial network dynamics, which 
reflects cellular metabolic state, is important for embryonic development, 
synapse formation, and neurodegeneration. This study aimed to investigate 
mitochondrial network dynamics and its plausible association with abnormal 
cellular oxygen consumption in schizophrenia.
METHODS: Viable Epstein-Barr virus (EBV)-transformed lymphocytes 
(lymphoblastoids) from DSM-IV diagnosed patients with schizophrenia (n = 17), BD 
(n = 15), and healthy control subjects (n = 15) were assessed for mitochondrial 
respiration, mitochondrial dynamics, and relevant protein levels by oxygraph, 
confocal microscopy, and immunoblotting, respectively.
RESULTS: Respiration of schizophrenia-derived lymphoblastoids was significantly 
lower compared with control subjects, and was twice as sensitive to dopamine 
(DA)-induced inhibition. Unlike DA, haloperidol inhibited complex I-driven 
respiration to a similar extent in both schizophrenia and the control cells. 
Both drugs interact with complex I but at different sites. At the site of DA 
interaction, we found alterations in protein levels of three subunits of complex 
I in schizophrenia. In addition, we observed structural and connectivity 
perturbations in the mitochondrial network, associated with alterations in the 
profusion protein OPA1, which was similarly reduced in schizophrenia prefrontal 
cortex specimens. None of these alterations were observed in the BD cells, which 
were similar to control cells.
CONCLUSIONS: We show impaired mitochondrial network dynamics associated with 
reduced cellular respiration and complex I abnormalities in schizophrenia but 
not in BD. If these findings represent disease-specific alterations, they may 
become an endophenotype biomarker for schizophrenia.