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)

Human chromosome Xp11.3-Xp11.23 encompasses the map location for a growing number of diseases with a genetic basis or genetic component. These include several eye disorders, syndromic and nonsyndromic forms of X-linked mental retardation (XLMR), X-linked neuromuscular diseases and susceptibility loci for schizophrenia, type 1 diabetes, and Graves' disease. We have constructed an approximately 2.7-Mb high-resolution physical map extending from DXS8026 to ELK1, corresponding to a genetic distance of approximately 5.5 cM. A combination of chromosome walking and sequence-tagged site (STS)-content mapping resulted in an integrated framework and transcript map, precisely positioning 10 polymorphic microsatellites (one of which is novel), 16 ESTs, and 12 known genes (RP2, PCTK1, UHX1, UBE1, RBM10, ZNF157, SYN1, ARAF1, TIMP1, PFC, ELK1, UXT). The composite map is currently anchored with 89 STSs to give an average resolution of approximately 1 STS every 30 kb. By a combination of EST database searches and in silico detection of UniGene clusters within genomic sequence generated from this template map, we have mapped several novel genes within this interval: a Na+/H+ exchanger (SLC9A7), at least two zincfinger transcription factors (KIAA0215 and Hs.68318), carbohydrate sulfotransferase-7 (CHST7), regucalcin (RGN), inactivation-escape-1 (INE1), the human ortholog of mouse neuronal protein 15.6, and four putative novel genes. Further genomic analysis enabled annotation of the sequence interval with 20 predicted pseudogenes and 21 UniGene clusters of unknown function. The combined PAC/BAC transcript map and YAC scaffold presented here clarifies previously conflicting data for markers and genes within the Xp11.3-Xp11.23 interval and provides a powerful integrated resource for functional characterization of this clonally unstable, yet gene-rich and clinically significant region of proximal Xp.
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PMID:An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders. 1194 89

N-methyl-D-aspartate (NMDA) glutamate receptor antagonists are used in clinical anesthesia and are being developed as therapeutic agents for preventing neurodegeneration in stroke, epilepsy, and brain trauma. However, the ability of these agents to produce neurotoxicity in adult rats and psychosis in adult humans compromises their clinical usefulness. In addition, an NMDA receptor hypofunction (NRHypo) state might play a role in neurodegenerative and psychotic disorders, like Alzheimer's disease, bipolar disorder and schizophrenia. Thus, developing pharmacological means of preventing these NRHypo-induced effects could have significant clinically relevant benefits. NRHypo neurotoxicity appears to be mediated by a complex disinhibition mechanism that results in the excessive stimulation of certain vulnerable neurons. Here we report our findings that five agents (phenytoin, carbamazepine, valproic acid, lamotrigine, and riluzole), thought to possess anticonvulsant activity because they inhibit voltage-gated sodium channels, prevent NRHypo neurotoxicity. The ability of tetrodotoxin, a highly selective inhibitor of voltage-gated sodium channels, to prevent the same neurotoxicity suggests that inhibition of this ion channel is the likely mechanism of action of these five agents. We also found that three other anticonvulsants (felbamate, gabapentin and ethosuximide), whose mechanism is less clear, also prevent NRHypo neurotoxicity, suggesting that inhibition of voltage-gated sodium channels is not the only mechanism via which anticonvulsants can act to prevent NRHypo neurotoxicity. Several of these agents have been found to be of clinical use in bipolar disorder. It would be of interest to determine whether these agents might have therapeutic benefits for conditions in which a NRHypo state may exist.
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PMID:Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity. 1219 17

Prepulse inhibition (PPI) of the acoustic startle response is a measure of sensorimotor gating and is decreased in neuropsychiatric diseases, including schizophrenia. Hippocampal involvement in PPI has been the subject of several studies, in particular, as aberrant hippocampal activity has been associated with schizophrenia. In rats, chemical stimulation of the ventral hippocampus reduced PPI, while normal PPI was found following hippocampal lesions, suggesting that ventral hippocampal overactivity is detrimental for PPI, but that normal hippocampal activity does not contribute substantially to PPI. In the present study, we investigated the importance of hippocampal activity for PPI by examining PPI in Wistar rats with temporarily decreased hippocampal activity, aiming to avoid compensatory processes that may occur with permanent lesions. Bilateral ventral or dorsal hippocampal infusions of the gamma-aminobutyric acid A (GABA(A)) receptor agonist muscimol (1 microg/side) or the sodium-channel blocker tetrodotoxin (TTX, 10 ng/side) reduced PPI. This reduction is probably neuroleptic-resistant since haloperidol and clozapine did not antagonize the muscimol-induced decreases in PPI. PPI reduction by muscimol inhibition or TTX inactivation of the dorsal or ventral hippocampus indicates that hippocampal activity contributes to sensorimotor gating, suggesting intact PPI after permanent hippocampal lesions to reflect compensatory processes. The data are discussed with respect to hippocampal dysfunction in schizophrenia.
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PMID:Prepulse inhibition in rats with temporary inhibition/inactivation of ventral or dorsal hippocampus. 1221 40

A 30-year-old white man with schizophrenia developed anorexia and nausea, and was admitted to hospital for confusion and delirium. He was on olanzapine, 10 days prior to admission. On admission, typical neuroleptic malignant syndrome (NMS) developed with elevated body temperature (39.7 degrees C), obtundation, tremor, rigidity, diaphoresis, fluctuating pupillary diameter, tachycardia, labile hypertension, elevated serum creatine kinase and severe hypernatremia (190 meq/l). Olanzepine was stopped few days after admission to the hospital and the NMS manifestations resolved by hospital day 12. The patient had all of the major manifestations of NMS. There was no other likely explanation for his illness. This is the first case reported in which NMS was associated with olanzapine and extremely elevated levels of serum sodium. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:Neuroleptic malignant syndrome with olanzapine associated with severe hypernatremia. 1240 81

Bipolar disorder is ranked as the sixth most important worldwide cause of disability. Current treatment is based chiefly on lithium and/or anticonvulsants, of which sodium valproate is the most widely used. A significant minority of patients fail to respond fully to current treatments, particularly those with mixed mania and/or rapid cycling. Many patients are unable to tolerate the side-effects of current therapy in the long term, and adverse effects may contribute to the high rate of noncompliance observed in bipolar disorder. The shortcomings of current treatments are reflected in poor outcomes: two-thirds of patients with bipolar disorder require hospitalization on more than one occasion; employment and social functioning are significantly lower than in control groups; 93% of carers suffer at least moderate distress; and 25-50% of patients are believed to attempt suicide at least once. Bipolar disorder shares some features with schizophrenia, and several atypical antipsychotics have demonstrated efficacy in bipolar disorder. Quetiapine has a particularly favourable tolerability profile, with placebo-level extrapyramidal symptoms and prolactin levels across the entire dose range combined with a neutral effect on weight during long-term use, and may be a valuable treatment option in acute mania and bipolar disorder.
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PMID:Atypical antipsychotics in mood disorders. 1257 66

We studied the effects of a short-term hypertonic stimulus on plasma levels of the stress hormones adrenocorticotropin (ACTH), cortisol, prolactin, and the blood volume- and electrolyte-controlling hormones arginine vasopressin (AVP) and atrial natriuretic peptide (ANP). Seven patients suffering from chronic schizophrenia with negative symptoms and ten healthy control subjects were investigated by a 20-minute infusion of 10 ml/kg body weight of hypertonic (2.5%) versus isotonic (0.9%) saline. All patients, who were medication-free for at least one week prior to the study, and all control subjects participated in two investigations in randomized order according to a single-blind cross-over design. During hypertonic infusion, plasma osmolarity and sodium levels were increased similarly in both groups and significantly more than during isotonic saline. Hypertonic saline caused a significant increase of plasma ACTH, cortisol and prolactin in patients in contrast to controls. AVP and ANP plasma concentrations were elevated after infusion of hypertonic saline, however, only patients showed a significant rise in plasma ANP. These results show that a dysregulation of the hypothalamic-pituitary-adrenal (HPA) system in a subset of patients with chronic schizophrenia may become overt during an osmotic stimulation, indicating an increased sensitivity of patients with schizophrenia to osmotic stress.
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PMID:Neuroendocrine effects of a short-term osmotic stimulus in patients with chronic schizophrenia. 1258 82

Structural features of the hydrophobic compartment and external parts of the erythrocyte membrane, Na+ and K+ ATPase activity, intensity of the free-radical oxidation of lipids, and the surface relief of erythrocytes were studied in paranoic schizophrenia patients before and after a course of pharmacotherapy. It was established that the administration of neuroleptics in therapeutic doses does not cause damage of the erythrocyte membrane.
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PMID:[Structural-metabolic characteristics of erythrocyte membrane in patients with paranoid schizophrenia undergoing psychopharmacotherapy]. 1259 27

This study evaluated the safety and efficacy of divalproex sodium extended-release (ER) when patients were switched from therapy with divalproex sodium delayed-release (DR) to divalproex sodium ER. This open-label, 7-day study included 55 patients with bipolar disorder, major depression, schizophrenia, schizoaffective disorder, Alzheimer's disease, dementia, or intermittent explosive disorder. Baseline plasma valproate concentrations were determined, and patients received their usual morning dose of divalproex sodium DR. At 9:00 p.m. the same day, they received divalproex sodium ER at a dose equal to their total daily dose of divalproex sodium DR. Valproate concentrations were monitored, and efficacy was measured with the Positive and Negative Syndrome Scale (PANSS). Side effects were assessed using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale. Valproate concentrations for 52 patients remained within the therapeutic range. Inpatient PANSS scores significantly improved from baseline to final evaluation on all subscales. For the combined inpatient and outpatient populations, a small but statistically significant improvement from baseline to final evaluation was seen for positive, general, and total PANSS subscale scores. At study's end, patients reported a significant decrease in the number and severity of adverse events; 54 of 55 patients elected to continue therapy with once-daily divalproex sodium ER. This study suggests that divalproex sodium ER is at least as effective as the DR formulation for treating patients with psychiatric illness and may be better tolerated. The ER formulation offers the advantage of once-daily dosing, which may help improve compliance.
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PMID:Safety and efficacy of switching psychiatric patients from a delayed-release to an extended-release formulation of divalproex sodium. 1264 Feb 19

At the opportunity of celebrating the 100th Anniversary of the Japanese Society of Psychiatry and Neurology, I am filled with deep emotion when I recall the time only a few decades ago, when mental disorders were believed to be an illness of the mind without any disorder in the brain. It has now become apparent that a mental disease emerges from the malfunction of the brain's unique biological mechanisms, so that any mental disease can be cured or prevented if the cause of the malfunction is clarified. Analyses of intercellular as well as intracellular signal transduction and the mechanisms underlying gene regulation in brain cells have recently advanced markedly and have brought a marked improvement in the methods and technology for investigating pathogenesis of neurological and psychiatric diseases. These impressive results have been derived in the search for the cause of Parkinson's disease, Alzheimer's disease and spinocerebellar degeneration. Certain minor changes in the molecular structure of sodium channels have been found to cause epilepsy. It has also been revealed that ten particular sites in chromosomes harbor the remote cause of schizophrenia and depression. These sites are probably responsible for production of certain synaptic transmitters and modulators. Another major challenge in the field of psychiatry is to understand the unique symptoms exhibited by patients with psychiatric disorders, which requires research to head in a direction different from molecular and cellular brain science. It is a challenge similar to the very fundamental challenge of determining how our brain, which is composed of numerous brain cells, yields our mind (or, should I say, supports our mind). To understand the brain as a complex system is more difficult than researching its molecular and cellular machinery, and accordingly, the progress of research in this field has been slow. However, it is gradually gaining speed thanks to the improvement in non-invasive methods for measuring activities in conscious human brains as well as that to the establishment of computational models. For example, it is a major mystery why a schizophrenic patient experiences auditory hallucinations, but an interesting hypothesis is derived by considering activities of the thinking brain as a neural system. Under this hypothesis, we gather information from the outside world by using our sensory systems and establish its internal model in our brain. Thus, manipulation of the internal model to run a simulation is an important part of our thinking activities. When an internal model behaves abnormally, abnormal information is generated, which makes the patient mistake it for sound from the outside, thus causing auditory hallucinations. It is highly expected that substantial progress will be made in psychiatry through proposals of new hypothetical models such as this one as well as verification of them through non-invasive measurement of brain activities. In the near future, patients with mental disorders will most likely benefit from the results of this two-directional research in psychiatry. The expectation is high for the strong leadership of the Japanese Society of Psychiatry and Neurology to promote research in Japan. Effective research effort requires efficient collection of human materials and systematic survey of patients, which will inevitably increase the involvement of patients in basic research. Improvement of research environments such as by developing a method for assessing research ethics and upgrading brain banks is urgently needed.
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PMID:[Roles of brain science in psychiatry]. 1264 5

A 63-year-old African-American woman was admitted to the hospital with urosepsis and altered mental status. She had a history of schizophrenia and was treated with olanzapine 5 mg/day and lithium carbonate 300 mg 3 times/day. During her hospital stay, her sodium level and serum osmolality increased and her urine osmolality decreased, whereas her lithium levels remained within normal limits. Based on these findings, the patient was diagnosed with diabetes insipidus secondary to lithium therapy and was treated successfully with amiloride. Clinicians have been aware of lithium toxicity for many years and traditionally have administered thiazide diuretics for lithium-induced polyuria and nephrogenic diabetes insipidus. Recently, amiloride, a potassium-sparing diuretic, has been reported as a successful treatment for nephrogenic diabetes insipidus.
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PMID:Treatment of lithium-induced diabetes insipidus with amiloride. 1268 Apr 86


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