Anterior cingulate metabolism correlates with stroop errors in paranoid schizophrenia patients.

UNLABELLED: Using [O-15]-H(2)O PET Carter et al. (1997) reported that medicated patients with schizophrenia performing computerized single trial Stroop (1935) showed a reduction in the anterior cingulate activation response to the more attention demanding, incongruent Stroop condition. In that study, both patients and controls also showed a direct correlation between anterior cingulate activation and errors committed during incongruent trials of the task. In this study we follow up with an examination of paranoid schizophrenia outpatients and controls with very high resolution positron emission tomography (PET) and the longer half-life tracer [F-18]-fluorinated deoxyglucose (FDG) (Valk et al. 1990). All subjects (10 controls and 9 paranoid schizophrenia patients) were studied with FDG-PET while performing a computerized trial-by-trial version of the Stroop task during the uptake phase of the tracer (Carter et al. 1992). RESULTS: As in previous studies using the single trial Stroop, patients were able to perform the task but made more color-naming errors during incongruent trials than controls. The patients in the present study showed a trend towards increased metabolic activity in the right anterior cingulate cortex. In the patient group, but not in controls, the anterior cingulate glucose metabolic rate correlated positively with the total incongruent trial errors. CONCLUSION: These results are consistent with the hypothesis that the anterior cingulate plays a performance-monitoring role during human cognition. This study does not rule out a reduction in error sensitivity in this region of the brain in schizophrenia, as other studies have suggested, however the data show that in unmedicated patients with the paranoid subtype this function is preserved to some extent.

Temporal lobe metabolic differences in medication-free outpatients with schizophrenia via the PET-600.

Regional cerebral glucose metabolic rates (rCMRglc) were compared in 18 unmedicated outpatients with schizophrenia and 11 normal controls using high resolution positron emission tomography (PET) and the tracer [F-18]-2-fluoro-2D-deoxyglucose (FDG). From previous work we expected to see abnormal hippocampal rCMRglc in the patients, but no striatal abnormalities. Trial-by-trial Stroop cognitive task, which has been shown to activate the anterior cingulate, was performed within a day of the PET study. As our patients performed abnormally on the Stroop we tested for a correlation between the anterior cingulate rCMRglc and Stroop performance. We found no whole slice cortical average glucose metabolic abnormalities. As, predicted we found abnormally decreased left hippocampal rCMRglc in the patients. No striatal or cingulate rCMRglc abnormalities were noted in patients, but they demonstrated a highly positive correlation between anterior and cingulate rCMRglc and Stroop facilitation. Patients with higher Stroop interference had more prominent hippocampal metabolic decreases. These localized temporal lobe abnormalities could account for some of the patient's positive symptoms and are consistent with recent findings in the literature.

Reduced temporal lobe glucose metabolism in aging.

The results of a positron emission tomography study of regional cerebral metabolic rates of glucose are reported for 8 healthy old subjects (mean age, 66 yr; standard deviation [SD], 5) and 9 young subjects (mean age, 27 yr; SD, 4.6) using a high-resolution positron emission tomograph and the glucose metabolic tracer 18F-fluorodeoxyglucose. Older subjects showed significantly lower cerebral metabolic rates than did the young subjects, in anterior, middle, and posterior temporal neocortex and in mesial temporal cortex, with the largest differences occurring in anterior temporal cortex (temporal pole). The current findings may reflect either decreases in regional cerebral metabolic rates for glucose that occur with normal aging, or early indications of cognitive dysfunction that is associated with age-related disorders.

Tracer kinetic evidence for abnormal methyl metabolism in schizophrenia.

The original transmethylation hypothesis of schizophrenia has evolved with time and experiment to the present concept that a defect in the methyl-carbon metabolic pathway may be causative in this illness. Various researchers have proposed that specific steps in the methyl-carbon pathway may be defective, and have presented evidence to support these possibilities. We have tested the general concept of the hypothesis by administering methionine labeled with 11C or 14C in the S-methyl carbon to patients with schizophrenia and to controls and measured the expiration of 11CO2 and 14CO2. We found that the rate and total expiration of labeled CO2 were three times less in the patients than in the controls, with no overlap of data points in the two groups. Specific steps in the methylcarbon pathway that might be defective and produce the results seen here are discussed in light of this and other researchers' findings.

Cerebral and peripheral demethylation of psychotomimetics measured by expired 14CO2.

Demethylation of psychotomimetic compounds was measured by labeling each methyl and methoxy substitutent separately with 14C and injecting it into rats, intravenously and intracerebrally. Expired [14C]CO2 was measured continuously and the resultant multi-exponential curves yielded rates and integral demethylation. 5-Methoxy-N,N-dimethyltryptamine was not demethylated, eliminating one proposed metabolic pathway. 2,4,5-Trimethoxyphenalkylamines were demethylated less in the brain than peripherally, markedly so at the p-methoxy position, suggesting a possible biochemical site for endogenous induction of psychosis.

18Fluorodeoxyglucose PET in schizophrenia.

Six chronic schizophrenic patients and six age-matched controls were studied with 18fluorodeoxyglucose (18FDG) positron emission tomography (PET). All patients were scanned when they had been free of medication for at least 2 weeks. Comparisons were made between the groups on regional ratios of cortical 18FDG, with manual and automated measures. Only one of eight regions, the right temporal cortical region, showed a significant group difference, and this effect was not significant when adjustment was made for multiple comparisons. Secondary analyses suggest that ventricular enlargement and age may be associated with a relatively "hypofrontal" pattern of 18FDG.

Kinetics of trace element chromium(III) in the human body.

Chromium(III) has been reported to be an essential trace element involved in the control of glucose metabolism by insulin. We have studied the distribution and kinetics of intravenous [51Cr]chromium(III) in six human subjects using a whole-body scintillation scanner, a whole-body counter, and plasma counting. Principal concentrations were found in the liver, spleen, soft tissue, and bone. The data were fit to a model consisting of a plasma pool in equilibrium with fast (T1/2 = 0.5-12 h), medium (1-14 days), and slow (3-12 mo) compartments, and transfer rates were calculated for exchanges between compartments. Each of the imaged organs appeared to contain varying proportions of each compartment. Two patients with hemochromatosis, in which iron overload is postulated to exclude chromium transport, were found to have altered rate constants. The results should be useful in assessing the metabolism and nutritional requirement of chromium(III) in humans and its importance in disease processes such as diabetes.

Quantitative measurement of demethylation of 14C-methoxyl labeled DMPEA and TMA-2 in rats.

Some reports have suggested that methylation and demethylation of compounds related to 6-hydroxydopamine may be involved in endogenous mental disorder. We report the synthesis of 3,4-dimethoxyphenethylamine (DMPEA) and 2,4,5-trimethoxyphenylisopropylamine (TMA-2) with each methoxyl group separately labeled with 14C. The rate and percent demethylation of these two compounds, with five labeled positions, were determined in the rat. The results suggest that TMA-2 might be metabolized to a hydroquinone in vivo; a similar metabolic intermediate of the psychoactive compound DOM is known to give rise in vitro to an indole.

A potential new brain-scanning agent: 4-77Br-2,5-dimethoxyphenylisoproplamine (4-Br-DPIA).

A centrally active drug containing bromine has been synthesized with 82Br and 77Br and appears to concentrate in normal human brain tissues, suggesting its potential use as a brain-scanning agent.