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.