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)

Dopamine, noradrenaline, glutamate decarboxylase (GAD) and choline acetyl-transferase (CAT) were measured in post-mortem brain samples from more than 50 patients dying with a hospital diagnosis of schizophrenia and an equal number of controls. GAD was measured in 14 different brain regions, and was significantly lower in both control and schizophrenia patients who died following a protracted illness. If GAD values from patients who died suddenly were compared, no significant differences were observed between the control and schizophrenia groups. There was also no differences between the CAT values measured in 13 different brain regions in the two groups. Noradrenaline values were not different in the two groups in most limbic areas or in the caudate nucleus, but were elevated in the schizophrenic group in nucleus accumbens and in anterior perforated substance. These differences were not, however, statistically significant. On the other hand dopamine concentrations in nucleus accumbens and in anterior perforated substance were significantly elevated (by 34 and 95 per cent, respectively) in the schizophrenia group as compared with controls, although dopamine values were not different in caudate nucleus, putamen, septal nuclei or amygdala. The finding of elevated concentrations of dopamine in certain areas of the limbic forebrain in schizophrenia is discussed in relation to current hypotheses of the involvement of dopamine in this illness, and the difficulties of determining whether the observed changes are related to chronic treatment with antischizophrenic drugs.
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PMID:Increased dopamine concentration in limbic areas of brain from patients dying with schizophrenia. 45 44

Chronic administration of amphetamine to cats (twice daily, in doses increasing from 5 to 15 mg/kg over a 10-day period) elicited a number of behaviors, e.g., limb flick and abortive groom, characteristic of the action of hallucinogenic drugs and dependent on a depression of central serotonergic neurotransmission. This drug treatment produced large decreases (-40 to -60%) in central nervous system serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), when measured either 6 or 24 hr after the last amphetamine injection. The rate of limb flicking returned to a predrug level approximately 5 days after drug withdrawal, at which time 5-HT and 5-HIAA levels had returned to within 30 to 40% of base line. Both 5-HT and 5-HIAA returned to base-line levels within 14 days after drug withdrawal. Norepinephrine (NE), dopamine (DA) and DA metabolites were decreased 60 to 95% by chronic amphetamine treatment and showed little recovery within the 14 days after drug withdrawal. A second experiment examined the latency to onset of the behavioral and neurochemical changes with a constant dose of amphetamine (7.5 mg/kg, twice daily). Limb flicking was significantly increased above base-line levels following 3 days of amphetamine administration, at which time 5-HT and 5-HIAA levels were decreased 30 to 40%. NE, DA and DA metabolites were decreased approximately 50 to 90% by this treatment regimen. A third experiment examined the effects of a low dose of amphetamine (3.75 mg/kg), injected more frequently (every 6 hr for 6 days), to approximate the administration pattern in human amphetamine abuse. This treatment produced significant increases in limb flicking and abortive grooming on days 5 and 6 and resulted in 30 to 40% depletions of 5-HT and 5-HIAA. NE, DA and DA metabolites were decreased by approximately 50 to 90%. These data are discussed in relation to a role for serotonin in amphetamine psychosis and schizophrenia.
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PMID:Chronic amphetamine administration to cats: behavioral and neurochemical evidence for decreased central serotonergic function. 50 68

Basal serum amino acids (including central monoamine precursors), central monoamines, and hormones were studied in schizophrenic patients (drug-naive; n = 20; drug-withdrawn for 3 or more days, n = 67; neuroleptic-treated, n = 23) and healthy subjects (n = 90) to answer the following questions: (1) Do neuroleptic-withdrawn and neuroleptic-naive patients differ on these serum measures? (2) What are the effects of neuroleptic treatment on these measures? (3) On which variables do drug-free and neuroleptic-treated patients differ? Because serum amino acid, central monoamine, and hormone levels were similar in drug-naive and drug-withdrawn patients, data from these groups ("drug-free") were combined and compared to those of healthy subjects and neuroleptic-treated patients. Asparagine, citrulline, phenylalanine, and cysteine were higher, while tyrosine, tryptophan, and the ratio of tryptophan to competing amino acids were significantly lower in drug-free schizophrenic patients than in healthy subjects. Dopamine was increased, and melatonin and thyroid hormones were decreased in drug-free schizophrenic patients compared to healthy subjects. Norepinephrine, epinephrine, and prolactin were higher in neuroleptic-treated men compared to drug-free male patients or healthy men. These results are consistent with the hypothesis of dopaminergic overactivity in schizophrenia, which might be caused by altered amino acid precursor availability and could be related to the decrease in melatonin and reduction in thyroid hormone levels.
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PMID:Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects. 198 23

The functional organization of chemically transmitting synapses in the brain are described with special emphasis on recent studies demonstrating the localization of different transmitters to specific anatomical circuitries. The use of pharmacological tools for manipulating levels of chemical transmitters is referred to briefly, but particular attention is given to the problems of studying the function of these pathways with lesion techniques. Noradrenaline (NA) and dopamine (DA) are selected for detailed consideration and experimental evidence reviewed, suggesting that these two catecholamines in the forebrain serve different functions: NA with processes of attention essential for learning, and DA with the execution of appropriate responses. Hypotheses suggesting dysfunction of forebrain DA and NA systems in schizophrenia are discussed.
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PMID:Brain chemistry and behaviour. 744 6

A study on the biology of 'panic disorder,' which I have classified under the category of 'anxiety disorder,' made progress recently. In a genetic study, the hereditary of panic disorder was checked by a 'linkage and twins' study, and the anticipation of panic disorder was recognized as being the same as that which is also found in the psychiatric conditions known as schizophrenia and manic depression. A panic disorder patient regards the anxious sign of a model as ruinous, and this weakness in recognition has been duly noted. Therefore, I studied a patient showing a continuance state of 'hyper-sensitivity,' and compared this to a patient showing a 'sleep disorder.' Noradrenaline plays an important role in anxiety as suppression of the locus ceruleus (LN), the major NE-containing nucleus of the noradrenaline nervous system, brings on a calming effect. Yohimbine, however, which is an alpha 2 antagonist, is found to induce panic attacks. The fact that selective serotonin reuptake inhibitor (SSRI) suppresses panic attacks suggests that serotonin is connected with panic disorders. It is also thought that the 'raphe nucleus' is the site of origin of the serotonin nervous system, which participates in the control of anxiety. This suggests the participation of a gamma-aminobutyric acid (GABA) nervous system in which the administration of benzodiazepine at a high potency would be an effective agent against panic disorder. Cholecystokinin (CCK) is also suggested to have a connection with panic disorder as CCK-4 causes panic attacks. There has been no CCK antagonist found effective for an object- or time-oriented panic disorder at the present. It is thought that corticotropin-releasing factor (CRF) is released during a panic attack. The development of a new CRF receptor antagonist is needed. In addition to the studies on the neurotransmitters of the traditional type, such as noradrenaline, serotonin and GABA, studies on the neuropeptides, such as CCK and CRF have become important for future consideration. Understanding this, image studies such as MRI, SPECT, fMRI and PET have become highly desirable.
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PMID:[Neuropharmacological and genetic study of panic disorder]. 1049 83

Norepinephrine is one of the neurotransmitters which has been implicated in the pathogenesis of mood disorders and schizophrenia. The norepinephrine transporter (NET) gene may be a candidate gene for the study of the genetics of these disorders. In this study, 198 patients with schizophrenia and 100 patients with bipolar disorder were analysed for a silent mutation 1287 A/G, located in the coding region (exon 9) of the NET gene, to determine the association between this polymorphism of the NET gene and bipolar disorder or schizophrenia. No association was found between the studied polymorphism of the NET gene and either bipolar disorder or schizophrenia.
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PMID:A polymorphism of the norepinephrine transporter gene in bipolar disorder and schizophrenia: lack of association. 1209 6

Norepinephrine is believed to modulate CNS processing of environmental signals. However, its specific role in stimulus evaluation processes has not been delineated. We examined the effects of the alpha2 noradrenergic agents, clonidine and yohimbine, on ERP and performance measures of auditory information processing. Ten healthy participants performed a three-tone target detection experiment, receiving either placebo, 0.2 mg clonidine, or 30 mg yohimbine, in a double-blind randomized design. The principal locus of action of the noradrenergic agents occurred between 100 and 200 ms poststimulus. P200 latency was sped by yohimbine and slowed by clonidine, and the frontal P3a was shifted in tandem. Components related to target detection (N250 and P3b) were unaffected. The results suggest that norepinephrine modulates CNS mechanisms of selective attention to infrequent stimuli. This may be relevant for patients with schizophrenia, a subset of whom exhibit selective abnormalities of these same ERP components. Our results offer a possible link between these two sets of findings, suggesting that some patients with schizophrenia may have dysfunctional noradrenergic systems.
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PMID:Alpha2-noradrenergic effects on ERP and behavioral indices of auditory information processing. 1221 63

N-methyl-D-aspartate (NMDA)/glutamate receptor antagonists, such as phencyclidine (PCP), induce behavioral abnormalities (locomotor hyperactivity, sensorimotor gating deficits, impairments of cognition) in animals that are thought to model aspects of schizophrenia. The administration of PCP increases noradrenaline transmission in the rat prefrontal cortex, a brain structure required for normal cognitive processes. Noradrenaline, in turn, works through a set of receptors that have themselves been implicated directly in NMDA antagonist-induced deficits; we recently reported that the alpha-2 agonist, clonidine, is effective at preventing PCP-induced deficits of working memory and visual attention in rats. Here, we further investigated the role for alpha-2 adrenoreceptors in the effects of PCP on spatial working memory performance. The alpha-2 agonist clonidine (0.001-0.01 mg/kg, subcutaneously (s.c.)) produced a significant amelioration of PCP-induced working memory deficits; the effects of PCP (1.0 mg/kg, s.c.), but not clonidine, were reduced in noradrenaline-depleted rats. In addition, the alpha-2A-preferring agonist guanfacine (0.05-1.0 mg/kg, s.c.) dose-dependently prevented the deficits of spatial working memory performance produced by PCP. Although the highly selective alpha-2 receptor antagonist, atipamezole (ATI), failed to affect spatial working memory on its own, at the doses studied (0.1-0.5 mg/kg, s.c.), it dramatically enhanced the working memory deficit produced by PCP. These data indicate that alpha-2 adrenoreceptors tonically inhibit PCP-induced deficits of spatial working memory, suggesting an important role for these receptors in cognitive deficits associated with NMDA receptor hypofunction.
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PMID:Alpha-2 adrenoceptor activation inhibits phencyclidine-induced deficits of spatial working memory in rats. 1571 23

A large body of evidence suggests that suicidal behavior is associated with altered noradrenergic neurotransmission. Norepinephrine is degraded by monoamine oxidase A (MAOA) and catechol-O-methyl transferase (COMT). Our hypothesis is that the genes encoding MAOA and COMT might contain genetic variants conferring increased risk for suicidal behavior in schizophrenia and that both genes may interact each other. In order to test this hypothesis, we genotyped the promoter VNTR polymorphism in the MAOA gene and three COMT polymorphisms: -287A>G, Val/Met and 3'UTR C Ins/Del in a cohort of 270 schizophrenics in which 92 attempted suicide. No association between suicide attempt and the MAOA VNTR (P = 0.382), Val108/158Met (P = 0.788) or -287A>G (P = 0.420) polymorphisms was found, however, a slight significant finding was found for 3'UTR polymorphism (P = 0.050). Haplotype analysis for COMT gene revealed no association between suicide attempts and haplotype distribution (P = 0.451). As we tested for epistasis between MAOA VNTR and COMT Val/Met, we found no significant interaction in conferring risk for suicide attempts (P = 0.545). These results suggest that epistasis between MAOA and COMT genes may not influence suicidal behavior in patients with schizophrenia.
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PMID:Gene-gene interaction between MAOA and COMT in suicidal behavior: analysis in schizophrenia. 1672 19

The entorhinal cortex is closely associated with the consolidation and recall of memories, Alzheimer disease, schizophrenia, and temporal lobe epilepsy. Norepinephrine is a neurotransmitter that plays a significant role in these physiological functions and neurological diseases. Whereas the entorhinal cortex receives profuse noradrenergic innervations from the locus coeruleus of the pons and expresses high densities of adrenergic receptors, the function of norepinephrine in the entorhinal cortex is still elusive. Accordingly, we examined the effects of norepinephrine on neuronal excitability in the entorhinal cortex and explored the underlying cellular and molecular mechanisms. Application of norepinephrine-generated hyperpolarization and decreased the excitability of the neurons in the superficial layers with no effects on neuronal excitability in the deep layers of the entorhinal cortex. Norepinephrine-induced hyperpolarization was mediated by alpha(2A) adrenergic receptors and required the functions of Galpha(i) proteins, adenylyl cyclase, and protein kinase A. Norepinephrine-mediated depression on neuronal excitability was mediated by activation of TREK-2, a type of two-pore domain K(+) channel, and mutation of the protein kinase A phosphorylation site on TREK-2 channels annulled the effects of norepinephrine. Our results indicate a novel action mode in which norepinephrine depresses neuronal excitability in the entorhinal cortex by disinhibiting protein kinase A-mediated tonic inhibition of TREK-2 channels.
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PMID:Noradrenergic depression of neuronal excitability in the entorhinal cortex via activation of TREK-2 K+ channels. 1924 46


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