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)

The present study reporting on continuous melperone treatment of hitherto longest duration recorded in literature was conducted in order to reveal side effects of long-term melperone therapy. 50 patients, 24 females and 26 males, aged 37-102 (average: 81 years of age) were treated with melperone (Buronil, Bunil, Eunerpan) for 1 to 20 years. In most patients, daily dosage varied from 10 to 300 mg, total dosage ranging from 6510 mg to 1 662 225 mg, avr. 203 923 mg. Diagnoses were as follows: senile dementia (14), organic dementia (9), arterio-sclerotic dementia (8), schizophrenia (17) and nonspecific psychosis (2). The patients were examined for clinical side effects including abnormal ECGs and ophthalmological diseases. Biochemical laboratory tests comprised sedimentation rate, haemoglobin, leucocytes, creatinine, alanine-aminotransferase, gamma-glutamyl-transferase and bilirubin. The results were evaluated by a specialist in internal medicine and an ophthalmologist performed the examinations on the 20 patients who were able to cooperate. The conclusion was that no serious side effects were observed which could with any certainty be related to melperone therapy.
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PMID:Additional studies on side effects of melperone in long-term therapy for 1-20 years in psychiatric patients. 287 21

The concentrations of the excitatory amino acid, glutamate, the inhibitory amino acids, glycine and taurine, and the inactive amino acids, glutamine and alanine, were determined in cerebrospinal fluid samples from 12 neurological control and 17 chronic schizophrenic patients. No significant differences were observed in any amino acid between the study groups. Within the schizophrenic group, no differences were observed between paranoid and undifferentiated patients. The concentrations of these amino acids in samples obtained from six schizophrenic patients during drug-free as compared to haloperidol-treatment periods also did not differ. These results do not support the glutamate hypothesis of schizophrenia.
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PMID:Cerebrospinal fluid amino acid concentrations in chronic schizophrenia. 288 77

The authors have investigated the levels of free amino acids and of the total fraction of medium molecules in the blood serum of patients with the paranoid form of continuously progressive schizophrenia. It has been demonstrated that these parameters are different in clinically normal individuals versus schizophrenics. The concentrations of free amino acids were the highest in people aged 40 to 50 years (Cys, Ala, Lys, Asp, Thr, Tyr, Try, Val, Leu, Ile) being considerably lower in individuals aged 50 to 60 years (Cys, Ala, Tyr) and over 60 years (Lys, His, Asp, Tyr, Try) which corresponds to the highest activity of the process in patients aged 40 to 50 years and its stabilization in older age.
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PMID:[Free amino acids and the total middle molecule fraction of the blood serum in patients with continuously progressive paranoid schizophrenia undergoing treatment]. 336 87

The present study which reports on the hitherto longest continuous melperone treatment recorded in the literature, was conducted in order to reveal side effects of long-term melperone therapy. 17 female and 20 male patients, aged 33-97 years, most of them with the diagnoses: schizophrenia (11 patients), dementia organica (11 patients) and dementia senilis (11 patients) were treated with melperone (Buronil) in doses of 15--800 mg/day for 1 to 15 years. The patients were examined for clinical side effects, abnormal electrocardiograms and ophthalmological diseases as well as abnormal values in sedimentation rate, hemoglobin, leucocytes, creatinine, alanine-aminotransferase, gamma-glutamyl-transferase and bilirubin. Also the thymol reaction was done. The electrocardiograms and laboratory investigations were controlled by specialists in internal medicine and the eye diseases by an ophthalmologist. We did not find any severe side effects which could be related with any certainty to melperone therapy.
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PMID:Additional studies on side effects of melperone in long-term therapy for 1 to 15 years in psychiatric patients. 611 35

A limited number of rare missense mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene have been reported. They are associated with a variety of phenotypes including cerebral haemorrhage, multi-infarct dementia and Alzheimer's disease. We recently reported an alanine to valine mutation in codon 713 in a single case of chronic familial schizophrenia with cognitive deficits. Using denaturing gradient gel electrophoresis (DGGE) we have screened a cohort of 250 chronic schizophrenics for further mutations of exons 7, 16 and 17. None were found. Nevertheless recent evidence suggests that the 713 mutation is indeed pathogenic for the clinical phenotype observed; the mechanisms involved are outlined.
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PMID:Screening schizophrenic patients for mutations in the amyloid precursor protein gene. 804

We report two novel polymorphisms and a rare deletion variant in the human dopaine D4 receptor gene. The two polymorphisms are characterized by single base pair substitutions, namely a G-->C transversion changing codon 11 from GGG (encoding Gly) to CGG (encoding Arg) and a C-->T transition in position -11 upstream from the start codon. The Arg11 variant occurs at a frequency of about 1% and the C-->T transition at a frequency of about 7% in German control subjects (n = 148). Allele frequencies observed in patients suffering from schizophrenia (n = 256) and bipolar affective disorder (n = 99) were similar. The deletion variant is characterized by a 21 bp deletion affecting codons 36 to 42 coding for amino acids Ala-Ala-Leu-Val-Gly-Gly-Val located in the first transmembrane domain of the dopamine D4 receptor. The mutation was identified in a single individual suffering from obsessive-compulsive disorder and panic disorder. We were unable to detect the deletion in patients with schizophrenia and bipolar affective disorder, nor in healthy controls.
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PMID:Identification of two novel polymorphisms and a rare deletion variant in the human dopamine D4 receptor gene. 874 7

The human dopamine D2 receptor gene (DRD2) has three polymorphic variants that predict the amino acid substitutions Val96 --> Ala, Pro310 --> Ser, and Ser311 --> Cys in the receptor protein. We have investigated the ligand binding and signal transduction properties of these human D2 receptor variants by stably expressing them in cultured mammalian cells. The Cys311 and Ser310 variants of the human D2 receptor, which involve substitutions located in the third cytoplasmic loop, were markedly less effective in inhibiting cAMP synthesis than the most prevalent form (Pro310, Ser311). Despite this difference, the Cys311 and Ser310 variants couple to G proteins in CHO-K1 (Chinese hamster ovary) cells. The impairment of the Cys311 and Ser310 variants to inhibit cAMP levels thus appears to result from a reduced ability of those variant receptors to activate the appropriate Gi-like protein. The demonstration of substantial functional differences between DRD2 gene variants found in the human population might have important pharmacological implications given the widespread use of D2 receptor blocking drugs in the treatment of schizophrenia and other psychiatric disorders.
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PMID:Functional analysis of the human D2 dopamine receptor missense variants. 882 40

Patients with methylenetetrahydrofolate reductase (MTHFR) deficiency often show psychiatric manifestations. Since a common variant of the MTHFR gene, T677(Ala), responsible for the thermolabile MTHFR with less than 50% specific MTHFR activity, has been reported, we examined whether the T677 allele is associated with psychiatric disorders in an unrelated Japanese population consisting of 297 schizophrenics, 32 patients with major depression, 40 patients with bipolar disorder, and 419 controls. The genotype homozygous for the T677 allele was significantly frequently observed in schizophrenics with an odds ratio of 1.9 (P = 0.0006), and in patients with major depression with an odds ratio of 2.8 (P = 0.005). Our data suggest associations of the MTHFR gene variant with schizophrenia and depression in the Japanese.
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PMID:Methylenetetrahydrofolate reductase variant and schizophrenia/depression. 934 5

There has been increasing evidence that deranged superoxide dismutase (SOD) activities might be a risk factor for schizophrenia and/or tardive dyskinesia (TD). In the present study, we investigated the genetic association between a functional polymorphism (Ala-9Val) in the human manganese (Mn) SOD gene and schizophrenia or TD (192 schizophrenics: 39 with TD and 153 without TD; 141 controls). No significant differences in the allelic or genotypic distribution between schizophrenics and controls were observed. However, we did find a significant difference in genotypic distribution between schizophrenics with and those without TD (p =. 03). Moreover, decreased -9Ala (mutant) allele was found among patients with TD (p =.02; odds ratio = 0.29; 95% confidence interval = 0.10-0.83). In conjunction with previous findings of increased free radicals and decreased SOD activities in TD subjects, these results suggest that the -9Ala (high activity) MnSOD allele may play a role in protecting against susceptibility to TD in schizophrenics.
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PMID:Manganese superoxide dismutase gene polymorphism and schizophrenia: relation to tardive dyskinesia. 1088 43

Dopaminergic hypofunction in the medial prefrontal cortex (mPFC) has been associated with the aetiology of negative symptoms and cognitive dysfunction of schizophrenia, which are both alleviated by clozapine and other atypical antipsychotics such as olanzapine. In rodents, early life exposure to stressful experiences such as social isolation produces a spectrum of symptoms emerging in adult life, which can be restored by antipsychotic drugs. The present series of experiments sought to investigate the effect of clozapine (5-10 mg/kg s.c.), olanzapine (5 mg/kg s.c.), and haloperidol (0.5 mg/kg s.c.) on dopamine (DA) and amino acids in the prelimbic/infralimbic subregion of the mPFC in group- and isolation-reared rats. Rats reared in isolation showed significant and robust deficits in prepulse inhibition of the acoustic startle. In group-reared animals, both clozapine and olanzapine produced a significant increase in DA outflow in the mPFC. Isolation-reared rats showed a significant increase in responsiveness to both atypical antipsychotics compared with group-reared animals. In contrast, the administration of haloperidol failed to modify dialysate DA levels in mPFC in either group- or isolation-reared animals. The results also show a positive relationship between the potency of the tested antipsychotics to increase the release of DA in the mPFC and their respective affinities for 5-HT1A relative to DA D2 or D3 receptors. Finally, isolation-reared rats showed enhanced neurochemical responses to the highest dose of clozapine as indexed by alanine, aspartate, GABA, glutamine, glutamate, histidine, and tyrosine. The increased DA responsiveness to the atypical antipsychotic drugs clozapine and olanzapine may explain, at least in part, clozapine- and olanzapine-induced reversal of some of the major behavioral components of the social isolation syndrome, namely hyperactivity and attention deficit.
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PMID:Increased responsiveness of dopamine to atypical, but not typical antipsychotics in the medial prefrontal cortex of rats reared in isolation. 1154 34


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