Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia

In-vivo imaging studies and post-mortem studies have demonstrated an impair ment of energy metabolism in brains of patients with schizophrenia. Decreas ed oxidative metabolism has been consistently documented in the frontal lob es. However, the biochemical basis of these changes is unclear. The changes could be caused by reduced requirement of the cells for metabolic energy o r an abnormality in energy generation. Neurons generate energy through the respiratory chain in the mitochondria. The respiratory chain consists of fi ve enzyme complexes (I-V). The purpose of the present study was to assess m itochondrial function and test the hypothesis of an underlying oxidative ph osphorylation defect in schizophrenia. We analysed spectrophotometrically p ost-mortem brain specimens of frontal cortex, temporal cortex, basal gangli a, and cerebellum of 12 patients who met the DSM-TV criteria for schizophre nia and of 13 healthy controls for the specific activities of respiratory c hain enzymes in the mitochondria. The major finding was that the activity o f complex IV was significantly reduced in the frontal cortex (40.9 +/- 6.7 vs. 87.3 +/- 12, P = 0.003) and in the temporal cortex (39.5 +/- 6.8 vs. 78 +/- 10.8, P = 0.006) of schizophrenics. In addition, the activity of compl exes I + III was significantly reduced in the temporal cortex (2.2 +/- 0.6 vs. 4.4 +/- 0.5, P = 0.01) and basal ganglia (1.6 +/- 0.5 vs. 3.4 +/- 0.3, P = 0.015) in schizophrenia. All other enzyme activities showed no differen ces to healthy controls. The results confirm a defect of oxidative phosphor ylation in brains from patients with schizophrenia, which may contribute to impaired energy generation. (C) 2001 Elsevier Science B.V. All rights rese rved.