title: Evidence for impaired glucose metabolism in the striatum, obtained postmortem, from some subjects with schizophrenia.
abstract: 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 β 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 β subunit of pyruvate dehydrogenase were lower (Δ mean=-20%) and levels of pyruvate (Δ mean=+47%) and lactate (Δ mean=+15%) were significantly higher in the striatum from subjects with schizophrenia. Notably, in subjects with non-MRDS, striatal levels of β subunit of pyruvate dehydrogenase were lower (Δ mean=-29%), whereas levels of pyruvate (Δ mean=-66%), acetyl-CoA (Δ mean=-28%) and glucose (Δ mean=-27%) were higher, whereas levels of lactate (Δ mean=+17%) were higher in MRDS. Finally, discriminate analyses using levels the β subunit of pyruvate dehydrogenase and glucose, or better still, β 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.
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute for Neuroscience and Mental Health, Parkville, VIC, Australia.
authors.forename: B
authors.identifier: 0000-0001-7773-4473
authors.initials: B
authors.lastname: Dean
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute for Neuroscience and Mental Health, Parkville, VIC, Australia.|The Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Thomas
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute for Neuroscience and Mental Health, Parkville, VIC, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Scarr
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute for Neuroscience and Mental Health, Parkville, VIC, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Udawela
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000473:pathology* / Q000503:physiopathology*; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D049669:History, 16th Century; D049670:History, 17th Century; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000502:physiology; D012016:Reference Values; D012559:Schizophrenia / Q000145:classification / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D001786:Blood Glucose; D011976:Receptors, Muscarinic; D019344:Lactic Acid; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D030481:Pyruvate Dehydrogenase (Lipoamide); C111305:pyruvate dehydrogenase E1 beta subunit