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Mitochondrial enzymes in schizophrenia

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Abstract

The responses of brain metabolism and blood flow to stimulation are diminished in the dorsolateral prefrontal cortexes (DLPFCs) of schizophrenic patients. Reductions in mitochondrial enzymes underlie diminished metabolism in several neurodegenerative diseases. Thus, we tested whether reductions in selected mitochondrial enzymes could underlie the changes in schizophrenia. The activities of the pyruvate dehydrogenase complex (PDHC), aconitase, isocitrate dehydrogenase (ICDH), and the α-ketoglutarate dehydrogenase complex (KGDHC) were determined on DLPFCs from patients with schizophrenia (n=26) and normal nonpsychiatric disease controls (n=13). The enzyme activities (mU/mg protein; mean ± SEM) were similar (values for controls and schizophrenic patients, respectively) for PDHC (11.36 ± 1.5, 10.33 ± 0.8), aconitase (1.06 ± 0.1, 1.35 ± 0.2), ICDH (31.70 ± 2.7, 32.00 ± 2.6), and KGDHC (2.62 ± 0.4, 3.09 ± 0.3). Separate analyses of the patients matched for age or postmortem interval gave similar conclusions. Cognitive dementia rating scores correlated poorly with activities of PDHC, aconitase, ICDH, and KGDHC. In one schizophrenic patient, activity of aconitase was undetectable, and in two others KGDHC activity was very low. Both had low activities of ICDH. A reduced activity of these enzymes in a subgroup is consistent with other data, suggesting that some patients with schizophrenia have abnormalities in brain mitochondria. However, in schizophrenia, unlike a number of neurodegenerative diseases, reductions in the activities of the key mitochondrial enzymes KGDHC and PDHC are not frequent.

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Authors and Affiliations

  1. Department of Neurology and Neuroscience, Weill Medical College of Cornell University at Burke Medical Research Institute, 10605, White Plains, NY

    Parvesh Bubber, Hui Xu, John P. Blass & Gary E. Gibson

  2. Department of Psychiatry, New York Presbyterian Hospital, Weill Medical College of Cornell University, White Plains, NY

    Jicheng Tang

  3. Department of Psychiatry, The Mount Sinai School of Medicine, 10021, New York, NY

    Kenneth L. Davis

  4. Mental Illness Research, Education, and Clinical Centers (MIRECC), Bronx Veterans Affairs Medical Center, 10468, Bronx, NY

    Vahram Haroutunian

Authors
  1. Parvesh Bubber
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  2. Jicheng Tang
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  3. Vahram Haroutunian
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  4. Hui Xu
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  5. Kenneth L. Davis
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  6. John P. Blass
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  7. Gary E. Gibson
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Correspondence to Gary E. Gibson.

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These authors contributed equally in completing the current study.

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Bubber, P., Tang, J., Haroutunian, V. et al. Mitochondrial enzymes in schizophrenia. J Mol Neurosci 24, 315–321 (2004). https://doi.org/10.1385/JMN:24:2:315

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  • DOI: https://doi.org/10.1385/JMN:24:2:315

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