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

The 2-deoxyglucose method was employed in rats following either acute or chronic administration of d-amphetamine. The drug was given either by a single intravenous and/or repeated daily intraperitoneal injections or by osmotic pumps implanted subcutaneously. Each mode of administration resulted in a specific constellation of metabolic effects. Acute doses of d-amphetamine, 5 mg/kg, stimulated glucose utilization in a number of cerebral structures, particularly the components of the extrapyramidal motor system. No effects were observed in components of the mesolimbic dopaminergic system. Repeated daily doses of 5 mg/kg for 2 weeks had no effects unless the dosage was progressively increased to toxic levels of 15 mg/kg over a 3-week period. Dosage sustained by osmotic pumps (12-15 mg/kg/day for 1 week or 6-7 mg/kg/day for 2 weeks), however, resulted in a selected increase in glucose utilization in the nucleus accumbens, an important component of the mesolimbic system. This finding may be of significance to the mechanism of amphetamine psychosis, which is sometimes regarded as a model of schizophrenia and is considered to be evidence in support of the dopamine hypothesis of the disease.
 ...
PMID:Comparative effects of acute and chronic administration of amphetamine on local cerebral glucose utilization in the conscious rat. 684 62

The capability of positron computed tomography (PCT) to delineate the substructures of the brain and its facility for accurately measuring the local tissue radioactivity concentration allow the application of tracer kinetic models for the study of local cerebral function in man. This principle and an adaptation of the 14C-deoxyglucose (DG) model of Sokoloff et al. with 18F-2-fluoro-deoxy-D-glucose (FDG) is being used at UCLA. Brookhaven National Laboratory, University of Pennsylvania, NIH, and the Massachusetts General Hospital to determine the local cerebral glucose metabolic rate (LCMRGIc) in normal man at rest and during sensory activation and the changes that occur in patients with a variety of cerebral disorders. Kinetic studies with PCT have been employed to measure the rate constants of the model in different gray and white matter structures of the brain in both normal and ischemic states. The precision of the method in normals has been shown to be about +/- 5% for 1.5-2.0 sq cm regions of the brain. Studies in normals have yielded values for hemispheric CMRGIc that are in agreement with measurement using the Kety-Schmidt technique and LCMRGIc values in agreement with values in monkeys using DG autoradiography. Studies in volunteers subjected to visual and auditory stimulation are demonstrating the potential of this technique for investigating the human brain's response to different stimuli. STudies in patients with stroke show excellent correlation between the degree, extent, and particular structures involved and the clinical symptoms. The method consistently detected hypometabolism in cortical, thalamic, and striatal tissues that were dysfunctional due to deactivation or damage but which appeared normal on x-ray CT. Studies in patients with partial epilepsy have shown hypometabolic zones that highly correlated anatomically with interictal EEG spike foci and were associated with normal x-ray CT studies in 77% of the patients studied. The studies on epilepsy at UCLA have resulted in the integration of the LCMRGIc study into the clinical workup of patients with partial epilepsy that are candidates for surgical resection of their epileptogenic focus (effective June 1979). Studies on Huntington's chorea, Parkinson's disease, aphasia, dementia, schizophrenia, and tumors are in early stage of investigation but also are providing exciting new results. Further studies are needed to determine the role of the local function information obtained with the PCT-FDG method in elucidating the basic mechanism and the potential to aid in improving the approach to medical therapy.
 ...
PMID:Positron computed tomography studies of cerebral glucose metabolism in man: theory and application in nuclear medicine. 697 94

Local cerebral uptake of deoxyglucose labeled with fluorine 18 was measured by positron-emission tomography in eight patients with schizophrenia who were not receiving medication and in six age-matched normal volunteers. Subjects sat in an acoustically treated, darkened room with eyes closed after injection of 3 to 5 mCi of deoxyglucose 18F. After uptake, seven to eight horizontal brain scans parallel to the canthomeatal line were done. Scans were treated digitally, with a 2.3-cm strip peeled off each slice and ratios to whole-slice activity computed. Patients with schizophrenia showed lower ratios in the frontal cortex, indicating relatively lower glucose use than normal control subjects; this was consistent with previously reported studies of regional cerebral blood flow. Patients also showed diminished ratios for a 2.3-cm square that was positioned over central gray-matter areas on the left but not on the right side. These findings are preliminary; issues of control of mental activity, brain structure identification, and biologic and anatomic heterogeneity of schizophrenia remain to be explored.
 ...
PMID:Cerebral glucography with positron tomography. Use in normal subjects and in patients with schizophrenia. 697 19

No correlation was found between blood glucose and simultaneous measurements of plasma propranolol concentration in patients with schizophrenia, on a daily dose of 80 mg to 1800 mg of propranolol as an adjunct to phenothiazine medication. The Glucose Tolerance Test (GTT) in ten patients on propranolol and phenothiazines did not differ significantly from those of a matched control group on phenothiazine alone. Two patients with mild diabetes showed no significant change in their GTT after stopping propranolol. These observations accord with the view that relatively high doses of propranolol as an adjunct to phenothiazine medication in schizophrenia are safe from the standpoint of glucose metabolism. This does not apply to the insulin dependent diabetic who is in danger of severe hypoglycaemia when glycogenolysis is blocked by propranolol.
 ...
PMID:Propranolol and blood glucose: simultaneous measurements over a wide range of doses and the effect of propranolol on the glucose tolerance test. 699 33

Investigations were carried out on two groups of patients suffering from cyclophrenia, atypical psychosis and schizophrenia. Both groups as well as a control group consisted of 30 persons each. The first of the psychiatric groups was treated with lithium carbonate and neuroleptics during a period of time ranging from 6 months to 8 years. The second psychiatric group was treated only with neuroleptics. The following parameters were being specified: The level of cortisol, insulin, somatotropin (GH) and lithium in the blood serum and also the glucose level in blood. Furthermore, the influence of lithium carbonate upon cortisol secretion and GH after insulin stimulation was also examined. The results of our work prove that the long-lasting treatment with lithium, when proper doses are carefully chosen, does not cause any significant changes of all the examined parameters.
 ...
PMID:[Endocrinological aspects of long-term lithium therapy]. 701 1

An ongoing study of the phenomenology, genetics, neuropsychology, physiology (eye tracking, autonomic responsivity), neuroimaging, biochemistry, and pharmacology of childhood-onset schizophrenia is described, and pilot data are presented for the first 22 subjects. Differentiation from autism "spectrum" disorders and other poorly defined, severe neurodevelopmental disorders is needed. Eye tracking and autonomic results are similar to patterns seen in later-onset schizophrenia and possibly more striking. Magnetic resonance imaging showed larger left frontal ventricular horn area for the schizophrenia subjects, larger left caudate, and lack of normal caudate asymmetry. Fluorodeoxyglucose positron emission tomography during an auditory continuous performance task revealed decreased right parietal/occipital glucose metabolic rate in the schizophrenia subjects, which may be secondary to poor attentional performance, and increased glucose metabolic rate in three left frontal regions, a left parietal region, and the right putamen. Clozapine has been effective and well tolerated in an open trial with 12 adolescents who responded poorly to typical neuroleptics; 16 subjects have been enrolled in a double-blind comparison of haloperidol and clozapine. Longitudinal study of this narrowly defined and possibly more homogeneous group of very early-onset schizophrenia subjects will be relevant to current neurodevelopmental theories addressing the role of puberty, progression of pathology, and continuity or discontinuity with later-onset schizophrenia.
 ...
PMID:Childhood-onset schizophrenia: an NIMH study in progress. 770 Dec 77

Fibroblasts have emerged as one of the best systems in which to study several genetically inherited diseases. Their use avoids the contaminating effects of medication and other environmental factors. Moreover, fibroblast cells cultured in vitro can express several biochemical parameters which are characteristic of neuronal cells. We have studied fibroblast MAO-A and glucose oxidation and platelet MAO-B from schizophrenic patients and control subjects. Fibroblasts from schizophrenics showed an increased glucose oxidation in two different experiments conducted (122% and 126% compared to controls). No changes were found in the levels of fibroblast MAO-A or platelet MAO-B activity. Possibly these alterations in glucose oxidation may be associated with a generalized membrane abnormality which has been reported in schizophrenia.
 ...
PMID:Glucose oxidation and monoamine oxidase activity from the fibroblasts of schizophrenic patients and controls. 772 92

Hypofrontality or reduced activity in the prefrontal cortex, measured as reduced frontal perfusion or glucose uptake, has gained the status of an established finding in the medical literature on schizophrenia. Many relevant studies, however, have potential sources of bias, such as small subject numbers, or unreliable performance of activation tasks by the patients during the scanning procedure. Seventy patients with non-affective and non-organic psychoses were recruited--most qualifying for DSM III-R schizophrenia or schizophreniform psychosis (n = 60)--together with 20 healthy volunteers. They underwent single photon emission computed tomography with 99mTc-exametazime, carried out at rest. Tracer uptake was normalised to the occipital cortex. Group differences in tracer uptake were predicted in anterior regions of interest (prefrontal cortex and mesial frontal/cingulate cortex). Actively psychotic (including schizophrenic) patients not taking any drugs showed increased uptake in the prefrontal cortex. Reduced tracer uptake occurred in the mesial frontal cortex of schizophrenic patients, particularly if they were taking drugs. Relatively increased prefrontal tracer uptake associated with relatively decreased mesial frontal uptake characterised the patients in comparison with the controls. Generalised hypofrontality is, therefore, not a feature of schizophrenic patients at rest whether taking drugs or not.
 ...
PMID:Hypofrontality revisited: a high resolution single photon emission computed tomography study in schizophrenia. 773 53

In this paper a detailed argument will be advanced in support of the notion that schizophrenia is fundamentally a diabetic brain state, henceforth referred to as 'cerebral diabetes'. Many extraneous features of cerebral diabetes have been observed, including positron emission tomography (PET) scans which reflect abnormal distribution patterns and diminished supplies of glucose in the brain. Equally, empirical research has demonstrated that plasma levels of essential fatty acids and prostaglandins are abnormally low, and low levels of glycoproteins in the urine of cerebral diabetics have also been observed. In addition, cerebral diabetics manifest a wide range of disturbing physical symptoms, such as, impaired sexual function, temperature control, low blood pressure, disrupted sleep patterns, excessive thirst, poor memory, insensitivity to pain, and chronic unhappiness, all of which can be attributed to disrupted neuroendocrine function. Thus, in order to persuasively assert the redefinition of schizophrenia as 'cerebral diabetes', we shall first explicate glucose regulation and transport in the brain and then outline how this interacts with essential fatty acids and prostaglandins, neurotransmission, and the neuroendocrine system. In so doing, we shall provide a metabolic explanation for all the prominent symptoms currently known to be associated with cerebral diabetes and indicate some future therapeutic interventions.
 ...
PMID:Schizophrenia is a diabetic brain state: an elucidation of impaired neurometabolism. 773 17

This study tests the hypothesis that seriously violent offenders pleading not guilty by reason of insanity or incompetent to stand trial are characterized by prefrontal dysfunction. This hypothesis was tested in a group of 22 subjects accused of murder and 22 age-matched and gender-matched controls by measuring local cerebral uptake of glucose using positron emission tomography during the continuous performance task. Murderers had significantly lower glucose metabolism in both lateral and medial prefrontal cortex relative to controls. No group differences were observed for posterior frontal, temporal, and parietal glucose metabolism, indicating regional specificity for the prefrontal deficit. Group differences were not found to be a function of raised levels of left-handedness, schizophrenia, ethnic minority status, head injury, or motivation deficits in the murder group. These preliminary results suggest that deficits localized to the prefrontal cortex may be related to violence in a selected group of offenders, although further studies are needed to establish the generalizability of these findings to violent offenders in the community.
 ...
PMID:Selective reductions in prefrontal glucose metabolism in murderers. 749 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>