Evidence for impaired glucose metabolism in the striatum, obtained postmortem, from some subjects with schizophrenia

Studies using central nervous system tissue obtained postmortem suggest pathways involved in energy and metabolism contribute to the pathophysiology of schizophrenia; neuroimaging studies suggesting glucose metabolism is particularly affected in the striatum. To gain information on the status of pathways involved in glucose metabolism in the striatum, we measured levels of glucose, pyruvate, acetyl-CoA and lactate as well as the beta subunit of pyruvate dehydrogenase, a rate limiting enzyme, in the postmortem tissue from subjects with schizophrenia and age/sex-matched controls. The subjects with schizophrenia were made up of two subgroups, which could be divided because they either had (muscarinic receptor deficit schizophrenia (MRDS)), or did not have (non-MRDS), a marked deficit in cortical muscarinic receptors. Compared to controls, levels of beta subunit of pyruvate dehydrogenase were lower (triangle mean = -20%) and levels of pyruvate (triangle mean = + 47%) and lactate (triangle. mean = +15%) were significantly higher in the striatum from subjects with schizophrenia. Notably, in subjects with non-MRDS, striatal levels of beta subunit of pyruvate dehydrogenase were lower (. mean = -29%), whereas levels of pyruvate (triangle mean = -66%), acetyl-CoA (triangle mean = -28%) and glucose (triangle mean = -27%) were higher, whereas levels of lactate (triangle mean = +17%) were higher in MRDS. Finally, discriminate analyses using levels the beta subunit of pyruvate dehydrogenase and glucose, or better still, beta subunit of pyruvate dehydrogenase and glucose in combination with pyruvate, lactate or acetyl-CoA could separate subjects with non-MRDS from controls with high levels of specificity (up to 93%) and selectivity (up to 91%). Our data show the benefit of being able to study defined subgroups within the syndrome of schizophrenia as such an approach has revealed that changes in glucose metabolism may be a significant contributor to the pathophysiology of non-MRDS.