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)

Prefrontal cortical modulation of caudate nucleus dopamine release was investigated in the rhesus monkey using the in vivo microdialysis technique. Reliable and stable basal caudate nucleus dopamine levels were quickly attained within hours following insertion of the dialysis probes. High-potassium (60 mM) or tetrodotoxin (10 microM) infusions significantly altered caudate nucleus dopamine levels in the dialysate indicating that measured dopamine levels reflected impulse-dependent release from the presynaptic pool. Pharmacological augmentation of monoaminergic transmission in the sulcus principalis region of the prefrontal cortex resulted in significant alterations in caudate nucleus dopamine levels. Increase of monoaminergic activity by infusion of either D-amphetamine (100 microM) or cocaine hydrochloride (100 microM) resulted in a gradual and prolonged decrease in caudate nucleus dopamine levels. Similar decreases were noticed in caudate nucleus dopamine metabolite levels. The present results indicate that in non-human primates modulation of dorsolateral prefrontal cortical monoaminergic transmission results in alterations in dopamine levels in subcortical structures. This observation may have clinical implications for therapeutic management of certain neuropsychiatric disorders, particularly schizophrenia.
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PMID:Augmentation of prefrontal cortical monoaminergic activity inhibits dopamine release in the caudate nucleus: an in vivo neurochemical assessment in the rhesus monkey. 859 54

The effects of excitotoxic lesions of the prefrontal cortex on behavioural, neurochemical and molecular indices of dopamine function in the caudate nucleus were studied in the marmoset. The lesion, which encompassed both the lateral and orbital regions of prefrontal cortex, made the animals more sensitive to the performance disrupting effects of the dopamine releasing drug, D-amphetamine, in a variation of the object retrieval task. Specifically, following drug administration, the lesioned marmosets were less able to gain access to food reward in the minimum number of responses. Analysis of the nature of the errors suggested that the deficit was not due to inhibition of a prepotent response as the lesioned monkeys were just as likely to make a detour reach to the unopened side of the box as a direct "line-of-sight" reach into the unopened front of the box. Rather, the data indicated a general disorganization of behaviour. The enhanced behavioural responsiveness to manipulations increasing presynaptic dopamine function was accompanied by neurochemical changes indicating a reduced responsiveness, as revealed by in vivo microdialysis. Thus, in lesioned animals, whilst there were no effects on baseline levels of extracellular dopamine in dorsolateral caudate, evoked release, both to systemic D-amphetamine and to a local depolarizing pulse of potassium ions, was attenuated. These opposite effects of the prefrontal cortex lesion on behavioural and neurochemical indices of striatal dopamine function occurred in the absence of any changes in striatal dopamine receptors of the D1 and D2 subtype, as determined both by radioligand binding assays and measurements of messenger RNA using in situ hydridization techniques. These data provide further insight into the interactions between prefrontal cortex and striatal dopamine function in the non-human primate. In particular, when taken in the light of our previous studies they indicate that following prefrontal manipulations, concurrence between behavioural and neurochemical indices of striatal dopamine function depends, critically, on the behavioural task. These findings are discussed with respect to the growing body of evidence implicating abnormalities in frontostriatal neurotransmission in complex disorders such as schizophrenia.
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PMID:Contrasting effects of excitotoxic lesions of the prefrontal cortex on the behavioural response to D-amphetamine and presynaptic and postsynaptic measures of striatal dopamine function in monkeys. 927 88

A recent study has suggested that a polymorphism in the hKCa3 potassium channel may be associated with raised susceptibility to schizophrenia. Despite its modest statistical significance, the study is intriguing for two reasons. First, hKCa3 contains a polymorphic CAG repeat in its coding sequence, with large repeats more common in schizophrenics compared with controls. This is interesting in view of several repeat expansion detection (RED) studies that have reported an excess of large CAG repeats in psychotic probands. Second, the hKCa3 gene is a functional candidate gene because studies of antipsychotic and psychotogenic compounds suggest that glutamatergic systems modulated by SKCa channels may be important in schizophrenia pathogenesis. In the light of the above, we have tested the hypothesis of an association between schizophrenia and the hKCa3 CAG repeat polymorphism using a case control study design. Under the same model of analysis as the earlier study, schizophrenic probands had a higher frequency of alleles with greater than 19 repeats than controls (chi 2 = 2.820, P = 0.047, 1-tail). Our data therefore provide modest support for the hypothesis that polymorphism in the hKCa3 gene may contribute to susceptibility to schizophrenia.
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PMID:Further support for an association between a polymorphic CAG repeat in the hKCa3 gene and schizophrenia. 967 3

A 21-year-old patient developed rhabdomyolysis during his nineteenth week of treatment with clozapine for drug-resistant schizophrenia. No risk factors for rhabdomyolysis were found, but the calcium-dependent potassium efflux, normally responsible for membrane hyperpolarization and muscle refractoriness, was severely decreased in the patient's red blood cells. Clozapine is speculated to cause rhabdomyolysis in patients with defective calcium-activated K+ channels.
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PMID:Rhabdomyolysis associated with clozapine treatment in a patient with decreased calcium-dependent potassium permeability of cell membranes. 970 70

In a family-based association study we investigated transmission of a multiallelic CAG repeat in a novel neuronal potassium channel gene, hSKCa3, in 59 parent/ offspring trios. In contrast to recent reports of an association of moderately large repeats with schizophrenia in case-control studies, our findings indicate that short CAG repeats (< or=19 repeats) are transmitted at an increased frequency to schizophrenic offspring (p=0.014), particularly among familial cases (p=0.007). No evidence for a parent-of-origin effect was found. Multiallelic TDT procedure showed no association of individual CAG repeats to schizophrenia. Further studies using family-based designs should clarify whether hSKCa3 is a susceptibility factor to schizophrenia or co-segregates with a major disease gene in tight linkage.
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PMID:Short CAG repeats within the hSKCa3 gene associated with schizophrenia: results of a family-based study. 985 66

A possible association between the small conductance calcium-regulated potassium channel gene, hSKCa3, and schizophrenia has recently been described by Chandy et al using a case-control design with patients with schizophrenia (n=141) and matched controls (n = 158). The gene may be considered as an excellent candidate gene for psychiatric disorders, since it plays a role in modulating neuronal firing patterns by regulating the slow component of after hyperpolarisation. In addition, the gene contains a highly polymorphic trinucleotide sequence (CAG) within exon 1, which encodes a polyglutamine stretch. The possible contribution of unstable trinucleotide repeats to the development of psychiatric disorders has previously been discussed. Chandy et al reported an over-representation of alleles with higher repeat number in schizophrenics as compared to controls (P = 0.0035). In an attempt to replicate these findings, we have performed a family-based study with 193 offspring/parent combinations using a sample of 49 multiplex families (two or more affected siblings with parents) and a second sample of 83 simplex families (one affected offspring with parents). No evidence for the association of longer repeats with schizophrenia was obtained when each sample was tested separately or when both samples were combined and tested for transmission disequilibrium.
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PMID:Association between hSKCa3 and schizophrenia not confirmed by transmission disequilibrium test in 193 offspring/parents trios. 1039 17

Recently, case-control studies have suggested an association between the polymorphic CAG repeat in the neuronal potassium channel gene hSKCa3 and an increased susceptibility to schizophrenia, with larger repeats being overrepresented in schizophrenic patients. Therefore, we have examined the CAG repeat polymorphism in hSKCa3 and four adjacent microsatellite markers in 12 multiplex schizophrenia families. On performing the extended transmission/disequilibrium test (ETDT), neither allele-wise (P = 0.67) nor genotype-wise (P = 0.071) analysis yielded evidence to support linkage disequilibrium between schizophrenia and the hSKCa3 CAG repeat alleles. No significant results were produced performing parametric and non-parametric linkage analysis between schizophrenia and hSKCa3, as well as the four microsatellite markers. Thus, our study does not support the involvement of hSKCa3 in schizophrenia. Furthermore, we refined the physical localization on chromosome 1q21.3 using linkage analysis. No recombination was seen between markers D1S2624 and D1S1600 and the polymorphic CAG repeat in hSKCa3. LOD scores of 19.44 and 12.97, respectively, were obtained at a recombination fraction of 0.00.
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PMID:hSKCa3: a candidate gene for schizophrenia? 1041 88

Anticipation has attracted much interest and has been demonstrated in several neuropsychiatric disorders. For some disorders, this phenomenon has been found to correlate with the repeat number in large and unstable repeats (CAG/CTG). In addition, case control studies have suggested an increase in triplet repeat size in the psychoses. Recently, it was reported that the larger alleles (longer than 19 repeats) of the second potassium channel gene hSKCa3 are associated with schizophrenia in European and American samples. A similar trend, though not statistically significant, was also seen in bipolar disorder samples. This was further supported by an independent UK study.1 In this investigation, we have examined Irish familial schizophrenic patients, bipolar affective disorder patients and ethnically matched controls in an effort to replicate these findings. No significant differences between the patients and the control groups were observed. In addition, linkage analyses in the multiplex schizophrenic families showed no evidence for linkage or linkage disequilibrium. We concluded that the polymorphism of the second CAG repeat of the hSKCa3 gene is not a risk factor in schizophrenia or bipolar disorder, at least in the Irish population.
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PMID:No evidence to support the association of the potassium channel gene hSKCa3 CAG repeat with schizophrenia or bipolar disorder in the Irish population. 1052 23

A 36-y-o patient with schizophrenia, who had consumed gradually increasing quantities of oolong tea that eventually reached 15 L each day, became delirious and was admitted to a psychiatric hospital. After abstinence from oolong tea his delirium resolved. He was transferred to our hospital when he was discovered to have acute renal failure with hyponatremia (118 mEq/L) and severe rhabdomyolysis (creatine phosphokinase, 227,200 IU/L). On admission rhabdomyolysis had begun to improve despite a worsening of the hyponatremia (113 mEq/L). With aggressive supportive therapy, including hypertonic saline administration and hemodialysis, the patient fully recovered without detectable sequelae. The clinical course suggests that caffeine, which is present in oolong tea, was mainly responsible for the rhabdomyolysis as well as the delirium, although severe hyponatremia has been reported to cause rhabdomyolysis on rare occasions. We hypothesize that caffeine toxicity injured the muscle cells, which were fragile due to the potassium depletion induced by the coexisting hyponatremia, to result in unusually severe rhabdomyolysis. The possibility of severe rhabdomyolysis should be considered in a patient with water intoxication due to massive ingestion of caffeine-containing beverages.
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PMID:Severe rhabdomyolysis following massive ingestion of oolong tea: caffeine intoxication with coexisting hyponatremia. 1059 46

1. Increased water intake and output is more common among psychiatric patients, especially those with schizophrenia, than in the general population. Animal studies suggest that polydipsia and polyuria derive, in part, from dopamine dysregulation. Stimulated by these observations this study sought to elucidate relationships among water homeostasis, monoamine metabolism, and electrolyte excretion in schizophrenic patients with and without paranoid hallucinatory symptoms (PH vs. NP), thought to reflect hyper- and hypo-dopaminergic states respectively, and to compare these with those shown by patients with obsessive compulsive disorder (OCD). 2. 24 hr-urine samples for electrolyte, monoamine and metabolite measures were taken from 14 schizophrenic patients with PH symptoms, 13 with predominantly nonparanoid (NP) symptoms, 11 OCD patients and 27 healthy controls (matched for age, weight and creatinine production). Water intake and serum electrolytes was sampled during psychological testing. 3. PH patients drank 2-3 times more than the others in a 3-4 hr test, yet 24 hr-urinary volumes were 75% larger in both PH and NP patients than in the two comparison groups. 4. Daily potassium excretion was a bit higher in PH patients, but concentrations of sodium, potassium and phosphate tended to be lower in PH and NP patients than in the others. 5. Positive associations of electrolyte with homovanillic acid excretion were consistent across groups and not directly related to medication. But associations of electrolyte excretion with noradrenergic activity in controls were absent in psychotic patients and associations with serotonin in OCD patients were absent in the other groups. 6. Increased water intake and output in PH patients along with the disturbed association with noradrenergic metabolism are consistent with altered autonomic activity in these patients. 7. The independence of measures of water homeostasis from dopaminergic medication indicates that the associations in clinically responding PH patients of polydipsia with DA function (decreased DA levels) may be pertinent to this subgroup but not to schizophrenia in general.
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PMID:Subclinical polydipsia and polyuria in young patients with schizophrenia or obsessive-compulsive disorder vs normal controls. 1063 61


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