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)

Eleven schizophrenic patients and nine normal controls were studied using in vivo 31Phosphorous magnetic resonance spectroscopy (31P MRS) to test the hypothesis of metabolic asymmetry in the temporal lobes in schizophrenia. The controls did not demonstrate any asymmetry of phosphorous metabolite ratios, percentage of phosphorous metabolites, or pH. In the schizophrenics, however, phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP) and phosphocreatine/inorganic phosphate (PCr/Pi) effects appeared to primarily reflect higher ratios on the right side, while the percentage of beta-ATP appeared to primarily reflect higher relative concentrations in the left temporal lobe. Moreover, significant negative correlations were noted between total Brief Psychiatric Rating Scale scores and PCr/beta-ATP in both the right and left temporal lobes. These results support the hypothesis of an asymmetric distribution of 31P metabolites in the temporal lobe of schizophrenic patients, and also show an association between temporal lobe phosphorous metabolism and the severity of psychiatric symptomatology.
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PMID:31Phosphorus magnetic resonance spectroscopy of the temporal lobes in schizophrenia. 139 Dec 94

A number of studies have demonstrated alterations in the structure and function of the frontal cortex in some schizophrenic patients. The possible etiology and pathogenesis of these abnormalities are unknown, but genetic and developmental causes are frequently mentioned. Recent in vivo 31P NMR studies of the dorsal prefrontal cortex have been conducted in eleven neuroleptic naive, first episode schizophrenic patients and compared with normal controls of comparable age, educational level and parental educational level. The findings in the schizophrenic patients are different from those of normal IQ adult autistic patients of comparable age and Alzheimer's patients but similar to normal elderly controls. These studies show decreased frontal lobe utilization of adenosine triphosphate in the schizophrenic patients which suggests a hypoactive dorsal prefrontal cortex. In addition, indices of membrane phospholipid metabolism are altered in the schizophrenic patients. However, the findings in the schizophrenic patients are quite similar to those observed in normal elderly controls and to those that normally occur to a lesser degree during adolescence. The phospholipid alterations observed in the schizophrenic patients are compatible with either premature aging or altered timing and exaggeration of the regressive events which occur during normal brain development. The changes in high-energy phosphate metabolism observed in the schizophrenic patients may prove to be state dependent, but the changes in membrane phospholipid metabolism could be related to molecular changes that precede the onset of clinical symptoms and brain structural changes in schizophrenia. These findings suggest new avenues of thinking about the pathogenesis and treatment of schizophrenia.
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PMID:Molecular insights into schizophrenia. 152 18

Neurotensin (NT) is a tridecapeptide which fulfills many of the requisite criteria for a role as a central nervous system (CNS) neurotransmitter. It is closely associated with CNS dopamine neurons and has been shown to interact with dopamine at physiological, anatomical and behavioral levels. Neurotensin is colocalized with dopaminergic neurons in the hypothalamus and midbrain. In addition, it blocks behaviors associated with activation of the dopaminergic pathways. Centrally administered NT has been shown to mimic many of the actions of antipsychotic drugs. In addition, the concentration of NT in cerebrospinal fluid is decreased in patients with schizophrenia. Administration of clinically effective antipsychotic drugs increases concentrations of NT in the caudate nucleus and nucleus accumbens. NT has been shown to play a role in signal transduction by mostly mobilizing calcium stores following inositol phosphate formation. This has been linked to subsequent events in protein phosphorylation. Lipophilic NT receptor agonists may represent a novel approach to the development of a new class of antipsychotic drugs.
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PMID:The neurobiology of neurotensin: focus on neurotensin-dopamine interactions. 166 85

Post-mortem brain tissue was obtained from four patients with schizophrenia and five controls to study cell groups in the brain stem reticular formation. Cholinergic neurons in the pedunculopontine nucleus (PPN) and lateral dorsal tegmental nucleus (LDT) were labeled using nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry, while catecholaminergic neurons of the locus ceruleus (LC) were labeled immunocytochemically using an antibody to tyrosine hydroxylase. In schizophrenic patients, there were increased numbers of neurons in the PPN labeled by NADPH-diaphorase and reduced cell size in the LC. These results implicate the reticular formation as a possible pathophysiological site for at least some patients with schizophrenia. This also suggests that some of the deficits observed may be based on faulty neurodevelopment.
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PMID:The brain stem reticular formation in schizophrenia. 168 69

Stimulation of 5-HT2 receptors in mammals by agonists causes detrimental neurological, psychological, and circulatory effects. 5-HT2 antagonists block the elicited effects, but by themselves, they do not cause any apparent behavioral, neurological or subjective effects. However, 5-HT2 antagonists increase slow wave sleep and have a therapeutic action on impaired circulation, dysthymia, and negative symptoms in schizophrenia. Chronic treatment of rodents with various 5-HT2 antagonists was reported to cause an anomalous desensitization and 5-HT2 receptor down regulation. In this study we further investigated the 5-HT2 receptor regulation in vivo and in vitro by agonist and antagonist treatment. Treatment of rats with the 5-HT2 agonist, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) (2.5 mg/kg s.c., every 8 h), rapidly caused desensitization of the head twitch response (-20% and -80% after 2 and 4 injections) and a decrease in the number of frontal cortical 5-HT2 receptors labeled with [3H]ketanserin (-24% and -41%, 24 h after 2 and 4 injections). The receptor resynthesis/degradation revealed half-times of 5 days initially to 3 days in the later drug-free period. Administration of the antagonist ketanserin (2.5 mg/kg, s.c., every 8 h) 15 min before the agonist, antagonized the acute behavioral effect but did not prevent the 5-HT2 receptor down regulation after 4 treatments. In contrast, ketanserin by itself, given 4 times, caused a reduction in the Bmax-value of [3H]ketanserin binding by 19% and given 10 times it caused a reduction in the Bmax-values by 28% and 31% of [3H]ketanserin and [3H]DOB binding in the frontal cortex. Hence 5-HT2 receptors labeled by an antagonist and an agonist ligand were similarly decreased. In vascular smooth muscle cells in culture kept for at least 24 h in a serotonin-free medium before treatment, the 5-HT2 receptor mediated 5-HT-induced inositol phosphate formation, was rapidly desensitized by agonist treatment: -20% after 15 min and -80% after 1 h incubation of the cells with 10(-5) M 5-HT or DOM. After 2 h and 24 h treatment resensitization occurred with half-times of 5 h and 12 h, respectively. Pretreatment of the cells for 15 min or 24 h with 10(-7) M of the antagonists setoperone or ketanserin, followed by extensive washing, caused a reduction in the 5-HT-induced inositol phosphate formation by about 50% with setoperone and by 30% with ketanserin. Effects of 15 min and 24 h drug pretreatment were similar.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:5-HT2 receptors, roles and regulation. 225 9

1. Propranolol has been reported to be beneficial in treating patients suffering from a variety of diseases including migraine, psychosis and schizophrenia. The mode of action of propranolol in the treatment of the above diseases is not clear. 2. An investigation into the possible effect of propranolol on receptor activated inositol phospholipid hydrolysis was carried out using human neutrophils. Receptor activated inositol phosphate production by formyl-methionyl-leucyl-phenylalanine has also been studied. 3. DL-propranolol caused a time and concentration dependent increase in inositol phosphate generation which was similar to that obtained for chemotactic peptide in neutrophils. The EC50 for propranolol was 2 microM compared to 0.5 microM for chemotactic peptide. 4. These results indicate the possibility that propranolol has a direct action on inositol phospholipid hydrolysis in addition to its beta-blocking effect.
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PMID:Stimulation of inositol phosphate production by propranolol in human neutrophils. 322 51

In vivo 31Phosphorous magnetic resonance spectroscopic imaging (31P MRSI) was performed on 18 chronic schizophrenic patients and 14 normal controls to determine if there was asymmetry of high-energy phosphorous metabolism in the temporal lobes of schizophrenic patients. Temporal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated significantly higher right relative to left temporal phosphocreatine/adenosine triphosphate (PCr/ATP), phosphocreatine/inorganic phosphate (PCr/Pi), and PCr as well as significantly lower right relative to left temporal ATP. There were no asymmetries of temporal lobe phosphorous metabolites in the control group. In addition, both left temporal PCr and the degree of asymmetry of temporal lobe PCr were highly correlated with the thinking disturbance subscale of the BPRS. This study provides further support for temporal lobe metabolic asymmetry in schizophrenia and its possible association with clinical symptoms.
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PMID:Asymmetry of temporal lobe phosphorous metabolism in schizophrenia: a 31phosphorous magnetic resonance spectroscopic imaging study. 749 21

We used the PCR amplification technique in an attempt to characterize further the dopamine D2L receptor expressed in the prolactin-secreting pituitary MMQ cell clone, derived from the prolactin- and ACTH-secreting Buffalo rat 7315 alpha pituitary tumour. By semiquantitative PCR amplification we were unable to detect the mRNA encoding the D2S receptor isoform, which derives from the well-known process of alternative splicing, producing two D2 receptor subtypes (D2L and D2S) in such tissues as the anterior pituitary and the corpus striatum. Although the pharmacology of the D2 receptor has been established in many studies on both native receptors and transfected receptor isoforms, because of the lack of tissues naturally expressing only one receptor isoform, MMQ cells represent the first example of cells uniquely or prevalently expressing only the D2L receptor, conceivably coupled to its native transduction mechanisms. These considerations prompted us to evaluate the pharmacology and the second messenger systems known to be modulated by dopamine. Scatchard analysis of [3H]spiperone binding resulted in a linear plot, consistent with the existence of a single class of binding sites, with a Kd of 0.055 +/- 0.002 nM and a Bmax of 27 +/- 3.5 fmol/mg protein. Competition experiments confirmed the GTP-dependence and the order of potency for agonist and antagonist ligands consistent with binding to a D2 receptor. The inhibitory effects of dopamine on adenylyl cyclase activity, inositol phosphate production and intracellular free calcium concentrations, the latter presumably via the opening of K+ channels, and prolactin secretion, as well as the reversal of the effect by the D2-selective antagonist (-)sulpiride and pretreatment with pertussis toxin, are consistent with the known biological actions of dopamine at D2 receptors. Based on our observations, the MMQ cell line can be considered a useful tool for investigating ligand-receptor interactions to develop new selective dopaminergic D2L ligands for the therapy of dopamine-related disorders such as schizophrenia, depression, Parkinson's disease and drug addiction.
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PMID:Absence of D2S dopamine receptor in the prolactin-secreting MMQ pituitary clone: characterization of a wild D2L receptor coupled to native transduction mechanisms. 766 27

Epidemiological and anatomical studies support the theory that disturbances of brain development may play a contributory role in the etiology of schizophrenia. Anatomical findings suggest that the normal pattern of neuronal migration during development of the cerebral cortex may be affected in the brains of schizophrenics, with the implication that cortical connectivity and associative function will be disrupted. In the present investigation in matched schizophrenic and control brains, we examined a particular population of neurons found in the prefrontal cortex and underlying white matter and characterized by histochemical staining for the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase. In normal brains, these neurons are found in highest numbers in the white matter immediately deep to layer VI of the cortex where they remain from the subplate, an early formed, but transitory structure that plays a key role in cortical development and connection formation. The dorsolateral prefrontal area of schizophrenics showed a significant decline in nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in the superficial white matter and in the overlying cortex but a significant increase in these neurons in white matter deeper than 3 mm from the cortex. These findings are consistent with a disturbance of the subplate during development in which the normal pattern of programmed cell death is compromised and accompanied by a defect in the normal orderly migration of neurons toward the cortical plate. These are likely to have serious consequences for the establishment of a normal pattern of cortical connections leading to a potential breakdown of frontal lobe function in schizophrenics.
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PMID:Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development. 767 91

In vivo 31Phosphorus magnetic resonance spectroscopic imaging (31P MRSI) was performed on 20 chronic schizophrenic patients and 16 normal controls to determine if there were specific changes in high energy phosphorus and phospholipid metabolism in the frontal lobes of schizophrenic patients. Phosphorous metabolites were assessed in each of the left and right frontal as well as the left and right parietal lobes. Frontal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated higher phosphodiesters (PDE) and lower phosphocreatine (PCr) in both the left and right frontal regions compared to controls. There was also lower left frontal inorganic phosphate (Pi) in the schizophrenic group. No group differences were noted in the left or right parietal regions. In addition, right frontal PDE and right frontal PCr were highly correlated with the hostility-suspiciousness and anxiety-depression subscales of the BPRS. This study provides further support for altered frontal lobe phosphorous metabolism in schizophrenia.
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PMID:31phosphorus magnetic resonance spectroscopy of the frontal and parietal lobes in chronic schizophrenia. 782 12


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