Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amisulpride, a benzamide derivative with an atypical neuroleptic profile relieves the negative symptoms of schizophrenia when administered at low doses (50-150 mg). In an attempt to define the anatomical substrates involved in this action we have studied the effects of amisulpride on regional cerebral glucose utilisation (RCGU) in the awake lightly restrained rat, by quantitative autoradiography using [14C]2-deoxyglucose ([14C]2-DG). Amisulpride was administered 1 h before [14C]2DG i.v. injection, at a dose of 5 mg/kg which resulted in a striatal D2 receptor occupancy of 10% similar to that induced by doses of this compound used for the treatment of negative symptoms of schizophrenia. Amisulpride induced significant RCGU increases in cortical areas, in visual relays, in auditory structures and in several limbic structures. The pattern of changes in RCGU seen with amisulpride clearly differs from that of haloperidol, given at a dose resulting in a similar occupancy of striatal D2 receptors (0.01 mg/kg), which was mostly ineffective. The amisulpride-induced activation of RCGU in specific brain areas involved in the control of cognitive functions and motivational and emotional behavior, may at least in part, explain the efficacy of this compound in the treatment of negative symptoms of schizophrenia.
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PMID:Effects of amisulpride, an atypical antipsychotic which blocks preferentially presynaptic dopamine autoreceptors, on integrated functional cerebral activity in the rat. 936 23

Decreased frontal cortical glucose metabolism has been demonstrated in adult schizophrenics both at rest and while engaging in tasks that normally increase frontal metabolism, such as the Continuous Performance Test (CPT). The authors tested the hypothesis that adolescents with childhood onset schizophrenia would also demonstrate hypofrontality while performing the CPT. Cerebral glucose metabolism was examined in 16 adolescents (mean age 14.1 +/- 1.7) with onset of schizophrenia by age 12 (mean age at onset 9.9 +/- 1.8) and 26 healthy adolescents selected to be similar in age, sex and handedness using positron emission tomography and 18F-fluorodeoxyglucose. Patients with childhood onset schizophrenia made fewer correct and more incorrect identifications on the CPT. Region of interest analysis revealed no significant group differences in global cerebral glucose metabolism, but increased metabolic rate in supramarginal gyrus (F = 6.74, P < 0.05) and inferior frontal gyrus/insula (F = 7.09, P < 0.05) and decreased metabolic rate in middle frontal gyrus (F = 6.72, P < 0.05) and superior frontal gyrus (t = 2.04, P < 0.05) in schizophrenics. Comparison of effect sizes with an identically designed study of adult schizophrenics did not indicate more severe hypofrontality in childhood onset schizophrenia. Pixel-based analyses indicated a more complex pattern of group differences in cerebral metabolism with bilaterally increased cerebellar metabolic rate in childhood onset schizophrenics. These findings suggest that childhood onset schizophrenia may be associated with a similar, but not more severe, degree of hypofrontality relative to that seen in adult onset schizophrenia.
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PMID:Cerebral glucose metabolism in childhood onset schizophrenia. 943 71

Technologic advances in functional brain imaging have provided exciting and informative insights into the functional neuroanatomy and neurochemistry of schizophrenia. Using MR spectroscopy, it has been possible to examine in vivo brain metabolism and to relate observed changes to physiological processes occurring at a cellular level. Positron emission tomography and single photon emission computed tomography have revealed disturbances of cerebral blood flow and glucose metabolism in patients with schizophrenia. More recently, these tools have also proved most useful in studying the relative receptor occupancy of typical and atypical antipsychotic medications.
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PMID:Chemical and physiologic brain imaging in schizophrenia. 955 93

Brain laterality in schizophrenia has been examined through the application of functional neuroimaging methods. These methods have included the 133Xenon technique for measuring cerebral blood flow (CBF); positron emission tomography for assessing rates of glucose metabolism, CBF, and neuroreceptor functioning; single photon emission computerized tomography for studying CBF and neuroreceptors; and functional magnetic resonance imaging for measuring changes attributable to CBF. This article highlights the application of this technology in schizophrenia research, emphasizing more recent studies that have evaluated hemispheric differences. There is evidence for lateralized abnormalities in some studies that have examined this dimension. In general, the results implicate abnormalities in left hemispheric activity. Recent advances in basic and clinical neuroscience provide an opportunity for focused application of functional imaging in neurobiological studies of schizophrenia.
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PMID:Laterality in functional brain imaging studies of schizophrenia. 1009 18

Almost all the neurons in the brain are influenced by the excitatory amino acid glutamate. Glutamatergic neurotransmission has been associated functionally with a number of physiological processes and with certain pathophysiological processes, including schizophrenia. Imaging studies provide indirect evidence that glutamate may be involved in schizophrenia. Positron emission tomography scanning has shown a correlation between positive symptoms of schizophrenia and abnormalities of glucose metabolism in components of the limbic system with the highest concentration of glutamate receptors. Studies with ketamine, an anaesthetic that antagonises the N-methyl-D-aspartate (NMDA) glutamate receptor, show an exacerbation or worsening of positive symptoms when this drug is administered to patients with schizophrenia. Regional cerebral blood flow studies with ketamine show that the drug produces increased blood flow in the anterior cingulate cortex, the area where high concentrations of NMDA receptors exist and where alterations in glucose metabolism seem to occur in people with schizophrenia. Diminished glutamatergic neurotransmission in the hippocampal glutamate-mediated efferent pathways and cerebral dysfunction in the hippocampus and its target areas, particularly the anterior cingulate cortex, may underlie some of the clinical manifestations of schizophrenia.
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PMID:Glutamatergic aspects of schizophrenia. 1021 Nov 34

Risperidone (R 64 766, 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-pyperidinyl]ethyl )-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one) has superior effects in treating negative symptoms of schizophrenia and causes less extrapyramidal side effects than traditional antipsychotics. In this study, we employed the [14C]2-deoxy-D-glucose method to map local cerebral metabolic activity of rats acutely administrated i.p. with 0.0, 0.1, 0.5, 1.0 and 2.0 mg kg(-1) risperidone. Risperidone in the highest dose produced a reduction of glucose utilization in 11 of the 38 regions examined. The results showed that the regions with metabolic change are somewhat different from those results studied with microdialysis and the Fos immunohistochemistry. Among the nuclei with metabolic changes, the hippocampus and the mediodorsal nucleus of the thalamus may be related to the therapeutic action of risperidone and require further study.
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PMID:The effect of acute administration of risperidone on local cerebral glucose utilization in the rat. 1033

The purpose of this review is to indicate the role insulin plays in normal brain neurophysiology, together with the role insulin may play in the regulation of regional cerebral blood flow (rCBF). The relationship between sustained elevation of the inflammatory cytokines and brain insulin dysregulation, with respect to the serious mental disorders, is also discussed. It has been observed that, as the inflammatory cytokines increase, they exert a synergistic influence on insulin and somatostatin, by initially increasing and then decreasing insulin secretion. In the brain, increased levels of insulin result in increased glucose utilization and over-stimulation of the autonomic nervous system (ANS), while the inhibition of insulin secretion results in decreased glucose utilization and dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. It will further be argued that these alterations in brain insulin influence rCBF in the serious mental disorders such as schizophrenia and the affective disorders. It is hypothesized that insulin regulates rCBF either directly, or indirectly via GLUT4 in the hypothalamus now considered the glucose-sensing, insulin-sensing mechanism of the brain and the body. Thus, we shall propose that insulin plays an important role in normal neurophysiology and that sustained elevation of the inflammatory cytokines dysregulates insulin secretion, rCBF, ANS and the HPA-axis in serious mental disorders.
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PMID:The role of brain insulin in the neurophysiology of serious mental disorders: review. 1036 77

Previous investigations have found that increasing circulating glucose availability can increase memory performance in rodents, healthy humans, and individuals with dementia of the Alzheimer's type. In this study, patients with schizophrenia, healthy control subjects, and controls with bipolar affective disorder were tested using double-blind treatment with either 50 g anhydrous dextrose plus 4 mg sodium saccharin (for "taste") or 23.7 mg saccharin alone, followed by cognitive testing on a complex battery. At this glucose dose, verbal memory performance on a paragraph recall task was increased during the glucose condition relative to the saccharin condition in the patients with schizophrenia; this effect was not detected in either the psychiatric or normal controls. The results provide preliminary support for the hypothesis that memory performance can be improved in patients with schizophrenia by increasing circulating glucose availability and suggest the importance of further evaluation of therapeutic manipulations of glucose availability.
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PMID:Glucose-induced increase in memory performance in patients with schizophrenia. 1041 34

The regional cerebral glucose metabolic rates of clozapine-treated and fluphenazine-treated women with schizophrenia and normal controls were obtained by positron emission tomography (PET) using [18F]-2-fluoro-2-deoxy-D-glucose (FDG) as the tracer. The regional metabolic patterns were compared to each other and to the changes previously observed in men. In women, as in men, both clozapine- and fluphenazine-treatment were associated with lower metabolism in the superior prefrontal cortex and higher metabolism in the medial temporal lobe. In both men and women, clozapine treatment led to a greater lowering of inferior prefrontal cortex activity than fluphenazine, which was statistically significant in the larger male cohort. Fluphenazine led to higher metabolic rates in the lateral temporal lobe than clozapine did, but the differences between the two neuroleptics were not statistically significant in either group. The greatest differences in the female as compared to the male responses to fluphenazine and clozapine were in the cingulate and striatum. As compared to controls, the cingulate metabolic rates of women were reduced by 9.1% and 11.4% on clozapine and fluphenazine, respectively; whereas, men have a statistically nonsignificant reduction of 0.1% with clozapine and a 3.2% increase with fluphenazine. In men, fluphenazine was associated with a much greater elevation in basal ganglia metabolic rates than was clozapine, 23.5% as compared to 3.75%; whereas, in women, basal ganglia metabolic rates are nearly equally increased by fluphenazine (21.6%) and clozapine (15.1%).
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PMID:The brain metabolic patterns of clozapine- and fluphenazine-treated female patients with schizophrenia: evidence of a sex effect. 1051 59

Glucose is the principal energy substrate for the brain, and alterations in glucose availability can alter neuronal function, including cognitive performance. Investigators have previously demonstrated glucose-induced memory and attentional improvements in humans, including a previous report from this group in subjects with schizophrenia. However, the age- and dose-dependence of this effect in schizophrenia has not been addressed. This within-subjects, double-blind experiment evaluated the cognitive effects of placebo-controlled, multiple fixed-dose oral glucose administration (0 g, 25 g, 50 g, 75 g) in younger and older patients with schizophrenia (n = 20) and healthy age-matched controls (n = 20). Each dose condition was administered on a different morning after a 9-h fast, with cognitive testing and plasma sampling following dose administration on each day. Older patients demonstrated dose-dependent improvements in recall performance on a spatial delayed response task and reaction time on a delayed match to sample task, while younger patients had decreases in attentional performance at the 75-g dose compared to placebo. As in previous reports, patients demonstrated higher plasma glucose and insulin concentrations than controls in response to fixed glucose dosing. The results provide further evidence that glucose and/or insulin can regulate brain functions relevant to memory and attention, and suggest that systemic changes in glucose regulation in schizophrenia deserve further study.
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PMID:Age- and dose-dependent glucose-induced increases in memory and attention in schizophrenia. 1064 82


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