Cerebral glucose utilization and platelet mitochondrial complex I activity in schizophrenia: A FDG-PET study

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2007-05, Vol.31 (4), p.807-813
• Main Authors: Ben-Shachar, Dorit, Bonne, Omer, Chisin, Roland, Klein, Ehud, Lester, Hava, Aharon-Peretz, Judith, Yona, Ilan, Freedman, Nanette
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Biological and medical sciences; Blood Platelets - enzymology; Brain glucose and platelets mitochondrial complex I correlation; Case-Control Studies; Cerebral Cortex - metabolism; Electron Transport Complex I - metabolism; Female; Fluorodeoxyglucose F18 - pharmacokinetics; Glucose - metabolism; Humans; Male; Medical sciences; Middle Aged; Mitochondria - enzymology; Positron-Emission Tomography; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Radiopharmaceuticals - pharmacokinetics; Schizophrenia; Schizophrenia - diagnostic imaging; Schizophrenia - metabolism; Schizophrenia - pathology; Tissue Distribution; Tomography, Emission-Computed
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2006.12.025

Altered cerebral energy metabolism and mitochondrial dysfunction in periphery and in brain are implicated in the pathophysiology of schizophrenia. This study investigated whether cerebral glucose metabolism (rCGM) abnormalities are linked to altered mitochondrial complex I activity in the periphery, in schizophrenia. Sixteen schizophrenic patients, 8 with total positive PANSS score ≥ 20 (high positive schizophrenics; HPS), and 8 with total positive score ≤ 12 (low positive schizophrenics; LPS), and 8 healthy subjects, were analyzed for their complex I activity in platelets mitochondria and underwent FDG-PET scans at rest. Complex I activity was significantly increased only in HPS and was positively correlated with positive PANSS scores. Images were spatially normalized to an SPM template, their intensities normalized based on average brain activity. Hypermetabolism was observed in the basal ganglia, thalamus, amygdala, and brainstem of both patient groups compared with controls, and in LPS patients extended to parts of cerebellum, left and right cingulate gyrus, parietal and frontal lobes. rCGM in basal ganglia and thalamus significantly and positively correlated with complex I activity in the HPS. In the LPS, a negative correlation was identified in the cerebellum and brainstem. In the control group, however, no areas demonstrated significant positive or negative correlation. These results suggest that the correlation between peripheral complex I activity and rCGM in regions implicated in schizophrenia, could be a pathological factor that is differentially expressed in subgroups of schizophrenic patients.