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)

506 patients with schizophrenia, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria, were included in a long term treatment programme with remoxipride, a selective dopamine (D2)-receptor antagonist. This overview includes pooled data from all patients who have been treated long term with remoxipride in clinical trials, focusing on patients treated for more than 6 months (n = 283). Remoxipride was administered in daily doses of 75 to 600mg. The assessment tools were Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Simpson and Angus scale, Abnormal Involuntary Movements Scale (AIMS) for abnormal involuntary movements, adverse events/symptoms using a 26-item checklist, clinical chemistry, and haematology and cardiovascular investigations. The majority of patients had a long duration of illness (median 11 years). 67% of patients (340/506) withdrew from treatment before 12 months and 44% (223/506) stopped treatment before 6 months. The median BPRS total score decreased during the first 3 months from 23 to 12, and this level of improvement was maintained throughout the 12-month period. Treatment-emergent adverse events reported by more than 5% of the patients were insomnia, tiredness, drowsiness and tremor in the group treated for 6 to 12 months. No symptoms, including checklist extrapyramidal symptoms (EPS), were reported by more than 5% of patients treated for 12 months. Low frequencies of EPS according to the Simpson and Angus scale were seen in patients treated for more than 6 months (n = 147). A small but statistically significant reduction of the mean total AIMS score from baseline to last rating was observed. There were infrequent changes in heart rate, resting diastolic blood pressure and electrocardiogram (ECG). Clinical chemistry and haematology data showed no evidence of clinically significant changes over time during the 12 months of treatment. Among 506 patients, 7 suicides and 7 suicide attempts occurred during the study period. Other serious adverse events were abnormal liver function test (2 cases), gastrointestinal, urinary retention, status epilepticus (psychotic polydipsia), granulocytopenia (1 each) and myocardial infarction (5 cases). Remoxipride is of potential value as a drug which is both effective and well tolerated in the long term management of patients with schizophrenia.
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PMID:Tolerability of remoxipride in the long term treatment of schizophrenia. An overview. 832 49

We studied the distribution of puromycin-sensitive aminopeptidase (PSA) in well-defined human brain ares by Western immunoblot in an attempt to examine its possible role in schizophrenia. The schizophrenic brains were from suicide victims (n = 13) of either sex, with an age range of 30-60 yr (average 45). The controls were mostly victims of myocardial infarction (n = 12), of either sex and between 32 and 56 yr old (average 44). The brain regions were obtained within 48 h after death. After ultracentrifugation the PSA was quantified by Western blot analysis using a PSA antiserum. The distribution of the two most abundant antigens, MW 100 kDa (PSA-100) and 170 kDA (PSA-170), were compared. PSA-100 had peptidase activity, PSA-170 did not. PSA-100 was found in all of the region studied. In the control brain areas prefrontal cingulate and frontal cortices, thalamus, hippocampus, hypothalamus and outer globus pallidus contained significantly more PSA-100 than the corresponding areas from schizophrenic brain. PSA-170 was mostly found only in areas of schizophrenic brains. In three control brains, in one area of each, it could be detected, but the level in each of these regions was less than 30% of that in the corresponding schizophrenic area. PSA-170 was found in all the schizophrenic brains, in 20 of the 35 regions we studied, with parahippocampal cortex the highest (134 ng/g wet tissue) and frontal inferior cortex the lowest (9.3 ng/g wet tissue). It was not detectable in cerebral or cerebellar white matter. Our data show that the amounts and distribution of PSA-170, a protein of unknown function, is restricted mostly to schizophrenic brain areas. The difference is not due either to neuroleptic treatment of the patient or to the postmortem proteolysis of the brain samples.
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PMID:Changes in puromycin-sensitive aminopeptidases in postmortem schizophrenic brain regions. 884 44

In a multicenter, double-blind, parallel group trial, the efficacy of risperidone (RIS) was compared with a combination of haloperidol and amitriptyline (HAL/AMI) over 6 weeks in patients with coexisting psychotic and depressive symptoms with either a schizoaffective disorder, depressive type, a major depression with psychotic features, or a nonresidual schizophrenia with major depressive symptoms according to DSM-III-R criteria. A total of 123 patients (62 RIS; 61 HAL/AMI) were included; the mean daily dosage at endpoint was 6.9 mg RIS versus 9 mg HAL combined with 180 mg AMI. Efficacy results for those 98 patients (47 RIS; 51 HAL/AMI) who completed at least 3 weeks of double-blind treatment revealed in both treatment groups large reductions in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale (RIS 37%; HAL/AMI 51%) and the Bech-Rafaelsen Melancholia Scale total scores (RIS 51%; HAL/AMI 70%). The reductions in the Brief Psychiatric Rating Scale and the Bech-Rafaelsen Melancholia Scale scores in the total group were significantly larger in the HAL/AMI group than in the RIS group (p < 0.01), mostly because of significant differences in the subgroup of patients suffering from depression with psychotic features, whereas treatment differences in the other diagnostic subgroups were not significant. The incidence of extrapyramidal side effects as assessed by the Extrapyramidal Symptom Rating Scale was slightly higher under RIS (37%) than under HAL/AMI (31%). Adverse events were reported by 66% of RIS and 75% of HAL/AMI patients. The results of this trial suggest that the therapeutic effect of HAL/AMI is superior to RIS in the total group of patients with combined psychotic and depressive symptoms. However, subgroup differences have to be considered.
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PMID:Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome. 955 96

As outcomes research and clinical practice guidelines are more widely disseminated throughout the healthcare industry, what will happen to scientifically validated but less widely recognized psychosocial interventions? The authors critically review the issues involved in guideline development, primarily in terms of the criteria used for this development and the research available to determine which interventions should be included or excluded. Evidence is presented for the cost effectiveness of psychosocial treatments in areas ranging from schizophrenia, bulimia, borderline personality and panic disorder to the psychological aspects of such physical disorders as myocardial infarction and breast cancer.
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PMID:Practice guidelines and empirically validated psychosocial treatments: ships passing in the night? 1014 14

Type 2 diabetes mellitus and impaired glucose tolerance are associated with antipsychotic treatment. Risk factors for type 2 diabetes and impaired glucose tolerance include abdominal adiposity, age, ethnic status, and certain neuropsychiatric conditions. While impaired glucose metabolism was first described in psychotic patients prior to the introduction of antipsychotic medications, treatment with antipsychotic medications is associated with impaired glucose metabolism, exacerbation of existing type 1 and 2 diabetes, new-onset type 2 diabetes mellitus, and diabetic ketoacidosis, a severe and potentially fatal metabolic complication. The strength of the association between antipsychotics and diabetes varies across individual medications, with the largest number of reports for chlorpromazine, clozapine, and olanzapine. Recent controlled studies suggest that antipsychotics can impair glucose regulation by decreasing insulin action, although effects on insulin secretion are not ruled out. Antipsychotic medications induce weight gain, and the potential for weight gain varies across individual agents with larger effects observed again for agents like chlorpromazine, clozapine, and olanzapine. Increased abdominal adiposity may explain some treatment-related changes in glucose metabolism. However, case reports and recent controlled studies suggest that clozapine and olanzapine treatment may also be associated with adverse effects on glucose metabolism independent of adiposity. Dyslipidemia is a feature of type 2 diabetes, and antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, with agents such as haloperidol, risperidone, and ziprasidone associated with reductions in plasma triglycerides. Diabetes mellitus is associated with increased morbidity and mortality due to both acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. A progressive relationship between plasma glucose levels and cardiovascular risk (e.g., myocardial infarction, stroke) begins at glucose levels that are well below diabetic or "impaired" thresholds. Increased adiposity and dyslipidemia are additional, independent risk factors for cardiovascular morbidity and mortality. Patients with schizophrenia suffer increased mortality due to cardiovascular disease, with presumed contributions from a number of modifiable risk factors (e.g., smoking, sedentary lifestyle, poor diet, obesity, hyperglycemia, and dyslipidemia). Patients taking antipsychotic medications should undergo regular monitoring of weight and plasma glucose and lipid levels, so that clinicians can individualize treatment decisions and reduce iatrogenic contributions to morbidity and mortality.
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PMID:Hyperglycemia and antipsychotic medications. 1180 85

This study compared the risks of cardiovascular morbidity and mortality in people with schizophrenia who use antipsychotic medications to risks in individuals without schizophrenia in a large managed care organization. A sample of 1920 schizophrenia patients was matched by age, sex, date, and health plan to 9600 persons randomly selected from the health plan general membership. Death, myocardial infarction, arrhythmia, and new-onset diabetes were identified using a National Death Index search and medical claims records. The adjusted all-cause mortality rate in the group of treated schizophrenics was four times higher than in the control group regardless of whether patients were given a typical or an atypical antipsychotic medication. Users of typical antipsychotics had a fivefold higher risk of myocardial infarction than the control subjects. Among patients with schizophrenia, cardiovascular risk was inversely associated with intensity of use of antipsychotic drugs, suggesting that the observed risks may not be due to a simple or direct effect of drugs. Patients treated for schizophrenia had higher rates of new-onset diabetes than did the general population controls. This risk was most pronounced in persons with more intense exposure to drugs and appeared to be indistinguishable in users of typical antipsychotics, of atypical products, or of both.
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PMID:Serious cardiovascular events and mortality among patients with schizophrenia. 1471 72

Administration of certain drugs (for example, antiarrhythmics, antihistamines, antibiotics, antipsychotics) may occasionally affect myocardial repolarization and cause prolongation of the QT interval. We performed a whole genome association study of drug-induced QT prolongation after 14 days of treatment in a phase 3 clinical trial evaluating the efficacy, safety and tolerability of a novel atypical antipsychotic, iloperidone, in patients with schizophrenia. We identified DNA polymorphisms associated with QT prolongation in six loci, including the CERKL and SLCO3A1 genes. Each single nucleotide polymorphism (SNP) defined two genotype groups associated with a low mean QT change (ranging from -0.69 to 5.67 ms depending on the SNP) or a higher mean QT prolongation (ranging from 14.16 to 17.81 ms). The CERKL protein is thought to be part of the ceramide pathway, which regulates currents conducted by various potassium channels, including the hERG channel. It is well established that inhibition of the hERG channel can prolong the QT interval. SLCO3A1 is thought to play a role in the translocation of prostaglandins, which have known cardioprotective properties, including the prevention of torsades de pointes. Our findings also point to genes involved in myocardial infarction (PALLD), cardiac structure and function (BRUNOL4) and cardiac development (NRG3). Results of this pharmacogenomic study provide new insight into the clinical response to iloperidone, developed with the goal of directing therapy to those patients with the optimal benefit/risk ratio.
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PMID:Whole genome association study identifies polymorphisms associated with QT prolongation during iloperidone treatment of schizophrenia. 1852 Oct 91

An impaired glutathione (GSH) synthesis was observed in several multifactorial diseases, including schizophrenia and myocardial infarction. Genetic studies revealed an association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the catalytic subunit (GCLC) of the glutamate cysteine ligase (GCL). Disease-associated genotypes of this polymorphism correlated with a decrease in GCLC protein expression, GCL activity and GSH content. To clarify consequences of a decreased GCL activity at the proteome level, three schizophrenia patients and three controls have been selected based on the GCLC GAG TNR polymorphism. Fibroblast cultures were obtained by skin biopsy and were challenged with tert-butylhydroquinone (t-BHQ), a substance known to induce oxidative stress. Proteome changes were analyzed by two dimensional gel electrophoresis (2-DE) and results revealed 10 spots that were upregulated in patients following t-BHQ treatment, but not in controls. Nine corresponding proteins could be identified by MALDI mass spectrometry and these proteins are involved in various cellular functions, including energy metabolism, oxidative stress response, and cytoskeletal reorganization. In conclusion, skin fibroblasts of subjects with an impaired GSH synthesis showed an altered proteome reaction in response to oxidative stress. Furthermore, the study corroborates the use of fibroblasts as an additional mean to study vulnerability factors of psychiatric diseases.
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PMID:Skin fibroblast model to study an impaired glutathione synthesis: consequences of a genetic polymorphism on the proteome. 1904 95

We investigated the prevalence of coronary heart disease (CHD) and myocardial infarction (MI) in persons with DSM-IV psychotic disorders. We also examined cardiac conduction abnormalities, and the role of antipsychotic medication in them. The study was based on a nationally representative survey of 8028 persons aged 30 years or over from Finland. Diagnoses of CHD and MI were based on electrocardiographic findings, health examination, and register information. QTc was calculated using the Bazett formula, and Minnesota classification was used for conduction abnormalities. We found that large Q-waves suggesting past MI were significantly more frequent in persons with schizophrenia, while the prevalence of CHD in persons with psychotic disorders did not differ significantly from the remaining study sample. Prevalence of prolonged QTc interval was significantly increased in persons with schizophrenia and in users of typical antipsychotics. However, low-potency antipsychotic use but not diagnosis of schizophrenia remained an independent predictor of prolonged QTc interval in a logistic regression. Low-potency antipsychotic use was associated with ventricular conduction defects, and high-potency antipsychotic use with premature beats. Symptoms and signs of CHD should be actively monitored patients with schizophrenia, and the electrocardiogram should be monitored for all types of changes in persons receiving antipsychotic medication.
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PMID:Coronary heart disease and cardiac conduction abnormalities in persons with psychotic disorders in a general population. 1992 42

In order to translate specialized scientific information into available, relevant and useful knowledge for decision-makers in public health, the PRIMUS group has developed the on-line Interactive Atlas on Health Inequalities (IAHI), based on user's needs assessments and data availability. Built on multidimensional tables, the IAHI is an health information system which has the power to allow users, especially those concerned by health inequalities, to query rapidly and interactively large volumes of health data (in aggregated format) at different spatial and population levels and to produce meaningful results displayed as tables, graphs or maps almost instantly. Designed explicitly to reveal inequalities in health, the IAHI offers relevant information for understanding social and geographical health inequalities observed for myocardial infarction, osteoporotic fractures, diabetes, chronic pain, schizophrenia, and mood disorders. The IAHI is a powerful support tool for decision-makers, serving the long term goal of closing the gaps across sub-populations, in terms of prevalence of diseases, access to health care, treatments and health outcomes.
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PMID:The interactive atlas on health inequalities. 2268 39


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