Mitochondrial activity in the mapping of functional brain changes in schizophrenia

The main contributors to the search for functional brain changes in schizop hrenia in the past years have employed imaging techniques such as positron emission tomography (PET), single photon emission computed tomography (SPEC T), and magnetic resonance imaging (MRI). Our laboratory has)applied a nove l strategy involving the post-mortem measurement of the mitochondrial respi ratory chain enzyme cytochrome-c oxidase (COX) to address the question of r egional metabolic changes in schizophrenia. This approach is based upon a s trong body of evidence which indicates that neuronal COX is highly regulate d by the energy demands of the cell and as such represents an endogenous ma rker of cellular energy metabolism over time. Our original findings indicat ed that COX activity may be reduced in the striatum and frontal cortex cons istent with the concept that a state reduced activity in cortico-striatal c ircuits may underlie schizophrenia. Subsequent studies from our laboratory on the effects of neuroleptics, PCP, and methamphetamine on animals, have p rovided additional evidence that a state of dopaminergic overactivity or gl utamatergic underactivity produces a hypometabolic state similar to that wh ich is evident in the brains of schizophrenics.