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)

In chronic schizophrenic patients treated with phenothiazines (Chlorpromazine, Levomepromazine, Perphenazine) for long periods (average = 8 years), high density lipoprotein cholesterol (HDL-C) levels were significantly lower (P less than 0.001) compared with normal controls. The HDL subfractions showed that HDL3-C was significantly low (P less than 0.005) whereas HDL2-C was not. Both serum apo A-I and apo A-II levels were also low (P less than 0.005 and P less than 0.001, respectively) in schizophrenics treated with phenothiazines. The serum triglycerides (TG) level was significantly higher (P less than 0.05) in patients treated with phenothiazines than in controls. No significant differences in total cholesterol (TC), TG and HDL-C were found between users and nonusers of benzodiazepine in schizophrenic patients receiving phenothiazines. In addition to chronic schizophrenic patients, 8 new patients with schizophrenia and related diseases were studied. The serum HDL-C level decreased by 24% within 1 week following administration of phenothiazines. No significant differences were found in TC and TG levels for 10 weeks after initiation of phenothiazine administration.
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PMID:Decreased concentration of high density lipoprotein cholesterol in schizophrenic patients treated with phenothiazines. 614 20

The use of a structured diagnostic interview (The Schedule for Affective Disorders and Schizophrenia) with 58 consecutively admitted general adult psychiatric patients revealed that 62.1% of them abused alcohol and 58.6% had a substance use disorder. The drug abusers did not differ significantly from the nonabusers on mean psychoticism (Brief Psychiatric Rating Scale) scores. However, they received higher doses of antipsychotic agents (mean daily dose 1022 mg CPZ EQ (SD = 614) vs 609 mg CPZ EQ (SD = 481); z = 2.58, p < .01) to achieve stabilization. The clinical implications of this finding are discussed.
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PMID:Relationship between concurrent substance abuse in psychiatric patients and neuroleptic dosage. 763 11

In contrast to the well known chlorpromazine-induced cholestatic hepatitis, we report the case of a schizophrenic patient who presents a cytolytic hepatitis, without any prior hepatic disease. Mr G. was first hospitalized for depressive symptomatology. A pseudo-nevrotic schizophrenia was diagnosed. Pretherapeutic clinical and biological data were normal. A treatment with chlorpromazine 400 mg/day was given. At day 8, the patient was still anxious and began to be agitated. An increase to 500 mg/day of chlorpromazine posology and an addition of haloperidol 200 mg/day was implemented. At day 10, the following clinical symptoms appeared: 38.6 degrees C fever; headache; myalgia; epigastralgia and hypocondrium pain. Biological hepatitis disturbances (ALAT, 984 U/L; ASAT, 414 U/L) and hypereosinophilia with normal white cell count were found. Clinical and biological investigations were normal. Blood-culture, A, B, C hepatitis, HIV and CMV serologies were negative. Neuroleptic treatment was discontinued. Evolution to normality of the disturbances and biological data suggested a cytolytic hepatitis. Mr G... remained treated with flupentixol without side-effects. Phenothiazine-induced cholestatis is frequent, mild, and recovers spontaneously. The biological mechanism is supposed to be immunologic. Prevalence of biological hepatic disturbances is 10 to 20% with chlorpromazine in long-term treatment. More often, symptomatology is the same; jaundice, pruritus, abdominal pain, fever. Although pharmacological data suggest for a cytotoxic activity of phenothiazines, cytolytic hepatitis is poorly described. Maximum range of transaminase blood level reported in previous studies is about 400 U/l. This level is not clearly correlated with hepatic cell lysis. Few cases of hepatic necrosis have been reported. In all cases, preexistent hepatic injuries were observed. Chlorpromazine-induced cytolytic hepatitis is uncommon and cholestatic hepatitis mild. Biological hepatic parameters investigations remain necessary during neuroleptic treatment.
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PMID:[Cytolytic hepatitis during treatment with phenothiazines: apropos of a case]. 903 96

The aim of this study was to find the dosage and pattern of neuroleptic drug utilisation for the treatment of acute schizophrenia in a general psychiatry ward. This is an uncontrolled study involving 112 schizophrenic inpatients. Patients' socio-demographic variables, the type and peak daily doses of neuroleptics prescribed to them were analysed. Chlorpromazine was the most commonly prescribed drug. The peak mean daily dose required by the patients was equivalent to 537 mg of chlorpromazine; and 400 to 600 mg/ day of chlorpromazine or its equivalent was generally sufficient to treat acute psychosis. The majority of the patients received neuroleptics within this dose range. Low potency drugs were prescribed in lower doses than high potency drugs. Patients treated with depot preparation tended to receive higher doses of medication than those prescribed oral medication alone. The doses of neuroleptics were significantly correlated with duration of admission.
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PMID:Neuroleptic drug utilisation for acute schizophrenia. 910 62

Clozapine has been shown to have superior effectiveness compared with classic neuroleptics in treating refractory schizophrenia in Caucasians, but its efficacy and safety in Chinese have not been adequately studied. Forty Chinese schizophrenic patients were recruited in a 12-week, double-blind, comparative trial. Twenty-one patients were randomly assigned to clozapine treatment and 19 to chlorpromazine treatment. The average dose was 543 +/- 157 and 1163 +/- 228 mg/day for clozapine and chlorpromazine, respectively. The results showed that six clozapine-treated patients (28.6%) had more than 20% improvement in Brief Psychiatric Rating Scale score and were classified as responders, whereas none of the chlorpromazine-treated patients was classified as a responder. The degree of improvement in positive symptoms, negative symptoms and Brief Psychiatric Rating Scale scores in the clozapine group was inversely correlated with the severity of negative symptoms at entry into the trial. Two clozapine-treated patients were withdrawn from the study, one because of leukopenia and nausea, and the other because of vomiting and hypotension. Chlorpromazine treatment was prematurely discontinued in two patients, because of jaundice and over sedation in one, and because of severe weight loss in the other (9 kg). The rate of moderate-to-severe sialorrhea was high in clozapine-treated patients (28.6%). Two clozapine-treated patients and two chlorpromazine-treated patients showed significant improvement in previously existing tardive dyskinesia and one chlorpromazine-treated patient exhibited aggravation of tardive dyskinesia. The results of this study indicate that clozapine treatment might have advantages over chlorpromazine for Chinese schizophrenic patients who are refractory to typical neuroleptic treatment.
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PMID:A double-blind comparative study of clozapine versus chlorpromazine on Chinese patients with treatment-refractory schizophrenia. 924 67

The impact of premorbid social and intellectual functioning in childhood and early adolescence on the developmental course of schizophrenia is not sufficiently understood. In a retrospective case study (93 consecutive in-patients, 43 males and 50 females) of first-episode psychosis occurring in adolescence, the relationship between premorbid adjustment and short-term therapeutic outcome under treatment conditions was examined. All of the patients had a DSM-III-R diagnosis of schizophrenia (n = 56) or schizo-affective disorder (n = 37). The mean age of the patients at the time of the study was 15.8 (SD = 1.0). Premorbid functioning during childhood and early adolescence was assessed by using the Cannon-Spoor et al. Premorbid Adjustment Scale (PAS) and studied with respect to its prognostic relevance for short-term therapeutic outcome (eight weeks) under neuroleptic treatment (350-700 mg Chlorpromazin dose equivalent). Criteria for clinical outcome were obtained from the study by Pearlson et al. (1989) which defines three grades (complete remission, partial remission and no response), according to the degree of positive symptomatology. Statistical analysis was based on nonparametric variance analysis. Patients with complete remission of positive symptoms after eight weeks of therapy had experienced far better premorbid adjustment in early adolescence and in childhood. Diagnosis and gender did not bias this result. Our data suggest that premorbid social functioning is a crucial variable with regard to therapeutic outcome in first-episode psychosis. Previous studies have reported a relation between poor premorbid functioning and negative symptoms. We found premorbid adjustment related to the course of positive symptoms.
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PMID:Premorbid adjustment and remission of positive symptoms in first-episode psychosis. 944

Complexin (cx) I and II are homologous synaptic protein genes which are differentially expressed in mouse and human brain and differentially affected in schizophrenia. We characterized the distribution of cx I and II mRNAs in rat forebrain and examined whether their abundance, or the transcript of the synaptic marker synaptophysin, is affected by 14 days' administration of antipsychotic drugs (haloperidol, chlorpromazine, risperidone, olanzapine, or clozapine). Cx I mRNA predominated in medial habenula, medial septum-diagonal band complex, and thalamus, whereas cx II mRNA was more abundant in most other regions, including isocortex and hippocampus. Within the hippocampus, cx I mRNA was primarily expressed by interneurons and cx II mRNA by granule cells and pyramidal neurons. Localized cx II mRNA signal was seen in the dentate gyrus molecular layer, suggestive of its transport into granule cell dendrites. Antipsychotic treatment produced selective, modest effects on cx mRNA expression. Cx I mRNA was elevated by olanzapine in dorsolateral striatum and frontoparietal cortex, while the abundance of cx II mRNA relative to cx I mRNA was decreased in both areas by olanzapine and haloperidol. Chlorpromazine increased cx II mRNA in frontoparietal cortex and synaptophysin mRNA in dorsolateral striatum. In summary, the data have implications both for understanding the effects of antipsychotic medication on synaptic organization, and for synaptic protein expression studies in patients treated with the drugs.
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PMID:Expression of complexin I and II mRNAs and their regulation by antipsychotic drugs in the rat forebrain. 1081 97

Electrospray ionisation quadrupole ion-trap mass spectrometric (ESI-MS) characterisation of the anti-psychotic drugs chlorpromazine, trifluoperazine, flupenthixol, risperidone and the antidepressant/internal standard trimipramine is presented and possible mechanisms for the observed MSn fragmentation patterns proposed. A validated liquid chromatography (LC)-MS-MS method is then applied to the detection and determination of these drugs in the hair of a patient under clinical treatment for schizophrenia. Chlorpromazine, trifluoperazine and flupenthixol are identified and determined in this hair sample following alkaline degradation of the matrix, solvent extraction and LC-MS-MS using trimipramine as internal standard.
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PMID:Electrospray ionisation-mass spectrometric characterisation of selected anti-psychotic drugs and their detection and determination in human hair samples by liquid chromatography-tandem mass spectrometry. 1082

Expression profiling using methods of functional genomics can be used to investigate changes in gene transcription induced by drug treatment, which may lead to discovery of new potential drug targets. Antipsychotic agents alleviate symptoms of schizophrenia but the mechanism behind their clinical efficacy is unclear. We have used the PC12 cell line as a model to characterize effects of the antipsychotic drug chlorpromazine on gene expression using high-density complementary DNA array filters prepared from a rat brain entorhinal cortex complementary DNA library. Chlorpromazine treatment positively regulated the expression of several clones, five of which were selected for further characterization. Northern blotting experiments confirmed the increased expression of these genes after chlorpromazine treatment. Sequencing revealed that two clones were cytochrome c oxidase and three were novel genes. Characterization of the function of these genes could increase our understanding of the mechanisms of action of antipsychotic drugs, and might be beneficial for the development of more effective agents.
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PMID:A functional genomic study of the effects of antipsychotic agent chlorpromazine in PC12 cells. 1109 49

Patients with schizophrenia show impairments of attention and neuropsychological performance, but the extent to which this is attributable to antipsychotic medication remains largely unexplored. We describe here the putative influence of the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), the antipsychotic serum concentration of dopamine (DA) D2-blocking activity and the approximated central dopamine D2-receptor occupancy (DA D2-occupancy), on conditioned blocking (CB) measures of attention and performance on a neuropsychological battery, in 108 patients with schizophrenia (compared with 62 healthy controls). Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid versus non-paranoid diagnosis, and in female versus male patients (independent of symptom severity). Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB in non-paranoid patients. Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance of the trail-making and picture completion tests (negative) and the block-design task (positive) showed the functional importance of DA-related activity. High estimates of central DA D2-occupancy were related to impaired verbal fluency but were associated with improved recall of stories, especially in paranoid patients. This, the first study of its kind, tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB, verbal fluency) and temporal lobe functions (verbal recall) as well as in some non-verbal abilities mediated more in the right hemisphere in patients with schizophrenia.
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PMID:Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy. 1110 86


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