RT Journal
A1 Andreazza AC, Shao L, Wang J, Young L
T1 MItochondrial complex i activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2010
FD April 1
VO 67
IS 4
SP 360
OP 368
DO 10.1001/archgenpsychiatry.2010.22
UL http://dx.doi.org/10.1001/archgenpsychiatry.2010.22
AB Context 
    Accumulating evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of bipolar disorder and schizophrenia. It remains unclear whether mitochondrial dysfunction, specifically complex I impairment, is associated with increased oxidative damage and, if so, whether this relationship is specific to bipolar disorder.Objective 
    To evaluate whether decreased levels of the electron transport chain complex I subunit NDUFS7 are associated with complex I activity and increased oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder, schizophrenia, or major depressive disorder.Design 
    Postmortem prefrontal cortex from patients and controls were assessed using immunoblotting, spectrophotometric, competitive enzyme immunoassay to identify group differences in expression and activity of complex I, and in oxidative damage in mitochondria.Setting 
    University of British Columbia, Vancouver, Canada.Patients 
    Forty-five patients with a psychiatric disorder (15 each with bipolar disorder, schizophrenia, and major depressive disorder) and 15 nonpsychiatric control subjects were studied.Main Outcome Measures 
    Oxidative damage to proteins and mitochondrial complex I activity.Results 
    Levels of NDUFS7 and complex I activity were decreased significantly in patients with bipolar disorder but were unchanged in those with depression and schizophrenia compared with controls. Protein oxidation, as measured by protein carbonylation, was increased significantly in the bipolar group but not in the depressed or schizophrenic groups compared with controls. We observed increased levels of 3-nitrotyrosine in the bipolar disorder and schizophrenia groups.Conclusions 
    Impairment of complex I may be associated with increased protein oxidation and nitration in the prefrontal cortex of patients with bipolar disorder. Therefore, complex I activity and mitochondrial dysfunction may be potential therapeutic targets for bipolar disorder.