Mitochondrial pathology in human schizophrenic striatum: a postmortem ultrastructural study

Studies using in vivo imaging or microscopic analysis of autopsy specimens indicate abnormalities in the striatum of schizophrenics including lower striatal metabolism, a change which can be normalized by antipsychotic medication. To investigate the possibility that abnormalities in schizophrenia brain may be due, in part, to pathology in mitochondria, organelles which generate energy, postmortem brain tissue from schizophrenic and control cases was obtained from the Maryland Brain Collection. Mitochondria in electron micrographs of striatal neuropil were counted and digitized. The caudate and the putamen of the schizophrenic subjects contained significantly (P < 0.05) fewer (a decrease of approximately 20%) mitochondrial profiles throughout the neuropil than did normal controls. The numbers of mitochondrial profiles per axon terminal appeared lower in the subset of schizophrenics off-drug as compared to either the subset of schizophrenics on-drug or to controls, suggesting that neuroleptic treatment may normalize this measure. The structural integrity of mitochondrial profiles in the schizophrenic striata was not obviously different from that of controls. Fewer mitochondrial profiles suggest decreased energy demands or diminished capacity to respond to energy requirements in the structures that contain them. These data are consistent with other studies showing decreased metabolism in the striatum of schizophrenics and may identify, in part, the anatomical basis of this deficit.