Regional brain glucose metabolism in drug free schizophrenic patients and clinical correlates

Abstract

Regional brain glucose metabolism was investigated in healthy volunteers (n = 10) and in drug free schizophrenic patients (n = 20). The metabolism was determined by positron emission tomography (PET) with 11C-glucose as the tracer. Diagnosis of schizophrenia was made according to RDC and DSM III. Eight patients had their first psychotic episode, four patients had a subchronic course and eight patients had a chronic course with an exacerbation of their illness. Computed tomography (CT) of the brain were made in all the subjects. Regions of interest (n = 35) were drawn on displayed CT images and the marked regions were transferred to the corresponding slice of the PET examination. The PET investigation was made in a dimly lit, quiet room with the eyes of the subject covered. The time course of the 11C-glucose uptake was measured by a four ring PET scanner (PC-384-7B). Metabolic rates of glucose varied greatly among the schizophrenic patients investigated. The variance was significantly greater than that of the controls in most regions. Decreases in mean levels of metabolic rates were related to patients with subchronic or chronic courses. Changes in metabolism were not related to previous duration of neuroleptic treatment of the patients. Left-right asymmetries were found in the temporal lobe (area 22) and the basal frontal cortex (area 11), the metabolic rates of the patients being lower on the left side compared to the controls. Asymmetry of the metabolic rate of the amygdala in hebephrenic patients was the opposite of that found in paranoid patients and controls. Negative correlations between regional metabolic rates and autistic or negative symptoms were found. Thus, the lower the metabolic rate was, the more autistic the patient. Metabolic rates were not correlated to atrophic changes of the brain. No basis for a specific alteration in frontal cortical metabolism of schizophrenics was obtained. Changes in regional metabolic rates in schizophrenia are suggested to reflect disturbances in more general mechanisms which are of importance in neuronal function.

Neurometabolic Effects of Psilocybin, 3,4-Methylenedioxyethylamphetamine (MDE) and d-Methamphetamine in Healthy Volunteers A Double-Blind, Placebo-Controlled PET Study with [18F]FDG

“…From the viewpoint of the model psychosis paradigm, our results are in line with evidence in favor of an association between acute psychotic episodes and hyperactivity in frontal cortical regions (Wiesel et al 1987;Szechtman et al 1988;Cleghorn et al 1989;Ebmeier et al 1993;Parellada et al 1994). These findings are in contrast with the hypofrontality, which has repeatedly been reported in studies with chronic schizophrenic patients (Buchsbaum et al 1982;Farkas et al 1984;Cohen et al 1987;Volkow et al 1987;Weinberger et al 1988;Wolkin et al 1988;Buchsbaum et al 1990;Andreasen et al 1992;Wolkin et al 1992;Siegel et al 1993).…”

“…However, most of these studies were performed with chronically ill patients on various neuroleptic medications, and evidence has accumulated in favor of an association between hypofrontality and negative symptoms (Volkow et al 1987;Wolkin et al 1992). Some few studies with acutely ill patients presenting with positive symptoms failed to demonstrate hypofrontality and did, in part, demonstrate hyperfrontal metabolic patterns (Sheppard et al 1983;Wiesel et al 1987;Cleghorn et al 1989;Ebmeier et al 1993;Parellada et al 1994). Thus, a general link between acute, pharmacologically induced or naturally occurring psychotic states and hyperfrontal metabolic patterns may be hypothesized.…”

Clinical and Sensorimotor Gating Effects of Ketamine in Normals

“…However, this is not a consistent finding. In fact, studies in unmedicated acutely relapsed schizophrenics with robust positive symptoms have reported a hyperfrontal metabolic pattern (Volkow et al 1986;Wiesel et al 1987;Cleghorn et al 1989;Ebmeier et al 1993;Parellada et al 1994). The extent to which ketamine administration is an accurate model of brain metabolic changes in schizophrenia needs further clarification.…”

Exploring Frontal Lobe Dysfunction in Schizophrenia with Positron Emission Tomography

“…Howe ver, these findi ngs may be due to a biological difference between new-onset and chronic sch izo p hrenia. A recent report by Wiessel and coworkers (43) indicated that duration of illness was directl y correlated with degree ofhypofrontality.…”