Mitochondrial function is differentially altered in the basal ganglia of chronic schizophrenics

In the present study, we have applied a novel strategy involving the postmo rtem measurement of the mitochondrial respiratory chain enzyme cytochrome-e oxidase (COX; complex IV) to identify regional changes in energy metabolis m in the basal ganglia of chronic, medicated schizophrenics. COX activity w as decreased ill the caudate nucleus but increased in the putamen and nucle us acctrmbens. An increase in succinate dehydrogenase (complex II) was evid ent in the putamen and nucleus accumbens, but changes were not seen with NA DH dehydrogenase (complex I). An analysis of interregional correlations in energy metabolism revealed several anomalies in the connections between the caudate and putamen and the globus pallidus in schizophrenics. Results pro vide strong evidence that changes in baseline energy metabolism in specific regions of the basal ganglia may exist in the disease. Based upon the high degree of input it receives from associative cortical areas, results sugge st that a defect in the caudate may underlie certain aspects of cognitive d ecline in schizophrenics, it contrast, an increase in COX in the putamen, w hich receives extensive projections from the sensorimotor cortex, may refle ct an effect of chronic neuroleptic treatment on motor function. (C) 1999 A merican College of Neuropsychopharmacology. Published by Elsevier Science I nc.