Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 alpha-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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PMID:Mitochondrial enzymes in schizophrenia. 1545 45

Images of brain metabolism and measurements of activities of components of the electron transport chain support earlier studies that suggest that brain glucose oxidation is inherently abnormal in a significant proportion of persons with schizophrenia. Therefore, we measured the activities of enzymes of the tricarboxylic (TCA) cycle in dorsolateral-prefrontal-cortex from schizophrenia patients (N=13) and non-psychiatric disease controls (N=13): the pyruvate dehydrogenase complex (PDHC), citrate synthase (CS), aconitase, isocitrate dehydrogenase (ICDH), the alpha-ketoglutarate dehydrogenase complex (KGDHC), succinate thiokinase (STH), succinate dehydrogenase (SDH), fumarase and malate dehydrogenase (MDH). Activities of aconitase (18.4%, p<0.05), KGDHC (26%) and STH (28.2%, p<0.05), enzymes in the first half of the TCA cycle, were lower, but SDH (18.3%, p<0.05) and MDH (34%, p<0.005), enzymes in the second half, were higher than controls. PDHC, CS, ICDH and fumarase activities were unchanged. There were no significant correlations between enzymes of TCA cycle and cognitive function, age or choline acetyl transferase activity, except for aconitase activity which decreased slightly with age (r=0.55, p=003). The increased activities of dehydrogenases in the second half of the TCA cycle may reflect a compensatory response to reduced activities of enzymes in the first half. Such alterations in the components of TCA cycle are adequate to alter the rate of brain metabolism. These results are consistent with the imaging studies of hypometabolism in schizophrenia. They suggest that deficiencies in mitochondrial enzymes can be associated with mental disease that takes the form of schizophrenia.
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PMID:Abnormalities in the tricarboxylic acid (TCA) cycle in the brains of schizophrenia patients. 2112 35