Abstract
Alterations of multiple G protein-mediated signaling pathways are detected in schizophrenia. G protein-coupled receptor kinases (GRKs) and arrestins terminate signaling by G protein-coupled receptors exerting a powerful influence on receptor functions. Modifications of arrestin and/or GRKs expression may contribute to schizophrenia pathology. Cortical expression of arrestins and GRKs was measured postmortem in control and subjects with schizophrenia or schizoaffective disorder. Additionally, arrestin/GRK expression was determined in elderly patients with schizophrenia and age-matched control. Patients with schizophrenia, but not schizoaffective disorder, displayed a reduced concentration of arrestin and GRK mRNAs and GRK3 protein. Arrestins and GRK significantly decreased with age. In elderly patients, GRK6 was reduced, with other GRKs and arrestins unchanged. A reduced cortical concentration of GRKs in schizophrenia (resembling that in aging) may result in altered G protein-dependent signaling, thus contributing to prefrontal deficits in schizophrenia. The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder.
Copyright © 2011. Published by Elsevier Inc.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Arrestins / biosynthesis
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Arrestins / deficiency
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Arrestins / genetics
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Cohort Studies
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Female
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G-Protein-Coupled Receptor Kinase 2 / biosynthesis
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G-Protein-Coupled Receptor Kinase 2 / deficiency*
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G-Protein-Coupled Receptor Kinase 2 / genetics
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G-Protein-Coupled Receptor Kinase 3 / biosynthesis
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G-Protein-Coupled Receptor Kinase 3 / deficiency*
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G-Protein-Coupled Receptor Kinase 3 / genetics
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G-Protein-Coupled Receptor Kinase 5 / biosynthesis
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G-Protein-Coupled Receptor Kinase 5 / deficiency*
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G-Protein-Coupled Receptor Kinase 5 / genetics
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G-Protein-Coupled Receptor Kinases / biosynthesis
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G-Protein-Coupled Receptor Kinases / deficiency*
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G-Protein-Coupled Receptor Kinases / genetics
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Humans
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Male
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Middle Aged
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Prefrontal Cortex / metabolism*
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Prefrontal Cortex / physiopathology
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Psychotic Disorders / genetics*
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Psychotic Disorders / metabolism
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Psychotic Disorders / physiopathology
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Schizophrenia / genetics*
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Schizophrenia / metabolism
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Schizophrenia / physiopathology
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Young Adult
Substances
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Arrestins
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G-Protein-Coupled Receptor Kinase 3
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GRK2 protein, human
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GRK3 protein, human
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G-Protein-Coupled Receptor Kinase 2
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G-Protein-Coupled Receptor Kinase 5
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G-Protein-Coupled Receptor Kinases
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G-protein-coupled receptor kinase 6
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GRK5 protein, human