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)

Regulation of ER stress proteins, such as the 78-kilodalton glucose regulated protein (GRP78) by chronic treatment with mood stabilizing drugs suggests that this family of proteins may be involved in the pathophysiology of mood disorders. Indeed, increased levels of GRP78, GRP94, and calreticulin, a third member of the ER stress protein family, were found in temporal cortex of subjects with major depressive disorder who died by suicide compared with controls and subjects who died by other means. No such differences were found in subjects with other psychiatric disorders such as bipolar disorder or schizophrenia. These data suggest a potential role for ER stress proteins in severe depression that merits further study.
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PMID:Increased temporal cortex ER stress proteins in depressed subjects who died by suicide. 1069 61

In a 40-year old patient with schizophrenia treated with sustained-action perfenazine for schizophrenia, diabetes mellitus type 2 and hypertension developed when clozapine was added to the regimen. The blood sugar values and the blood pressure normalized when clozapine was discontinued two weeks later. When he was 44 years old, clozapine was resumed as the psychotic symptoms did not subside. Diabetes mellitus reappeared and did not disappear after discontinuation of the clozapine. Insulin therapy was necessary. An association between the emergence of diabetes mellitus and the use of clozapine is suggested. Previously 15 cases of diabetes mellitus emerging during treatment with clozapine were described in the international literature. Monitoring of blood glucose is advised in patients with a positive family history of diabetes mellitus or with a personal history of impaired glucose tolerance.
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PMID:[Diabetes mellitus after treatment with clozapine]. 1093 6

Previous research indicates that verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. However, the concomitant patterns of regional brain function associated with these deficits in schizophrenia are not well understood. The present study examined verbal-memory performance and simultaneous relative glucose metabolic rates (rGMR) with FDG PET in 20 unmedicated schizophrenia patients who met stringent memory-performance criteria and 32 age- and sex-matched normal volunteers. On a modified version of the California Verbal Learning Test, patients recalled fewer correct words using a semantic-clustering strategy and exhibited more intrusions compared with normal subjects. However, patients had higher serial-ordering strategy scores, indicating their use of a less efficient organizational strategy. Among patients, greater use of the serial-ordering strategy was associated with decreased rGMR in frontal cortex and increased rGMR in temporal cortex. Patients had lower rGMR primarily in frontal and temporal cortex, but not parietal and occipital lobe regions. Patients also exhibited hypofrontality (lower ratio of frontal to occipital rGMR) compared with normal subjects. Among the patients, more severe hypofrontality was associated with increased perseveration errors.
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PMID:Hypofrontality in unmedicated schizophrenia patients studied with PET during performance of a serial verbal learning task. 1082 13

Schizotypal personality disorder is the prototype of the schizophrenia-related personality disorders and has been demonstrated to have phenomenologic, biologic, treatment, and outcome characteristics similar to those of schizophrenic patients. These studies suggest that patients with schizotypal personality disorder, like schizophrenic patients, show cognitive impairment, but the impairment is more focal and involves primarily working memory, verbal learning, and sustained attention rather than generalized intellectual deficits. Schizotypal patients, like schizophrenic patients show reductions in temporal lobe volume, but seem to be spared the frontal volume reductions found in some studies of schizophrenic patients and in our laboratory. Better frontal "buffering" may prevent the more severe cognitive and social deterioration associated with schizophrenia. Furthermore, schizotypal patients appear to show less susceptibility to psychotic symptoms, in part perhaps because of better buffered subcortical dopaminergic activity as suggested by recent data from a SPECT/amphetamine paradigm, glucose metabolic study, and structural studies of basal ganglia. These findings are discussed in terms of a model of schizotypal personality disorder where schizotypal patients have better capacity for compensatory buffering in lateral and subcortical brain regions, protecting them from the more severe symptoms of chronic schizophrenia.
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PMID:New perspectives on schizotypal personality disorder. 1112 34

As a class, the atypical antipsychotics are the first line treatment choice for the psychopharmacologic management of psychotic disorders. Emerging evidence currently suggests that at least two of the atypical antipsychotics, clozapine and olanzapine, and possibly quetiapine may be associated with the risk of new onset diabetes or serum glucose dyscontrol. Computerized Medline and Current Contents searches from years 1966 through June 2000 were undertaken to retrieve all pertinent studies and case reports of typical and atypical antipsychotics and glucose-insulin problems. Historically, both schizophrenia and the older antipsychotics medications have been reported to be associated with a similar risk for causing disruptions in serum glucose control. Additionally, diabetes has well recognized associations with a number of medical disorders such as cardiovascular disease; it is therefore worthy of attention. Hypothesized mechanisms for antipsychotic induced diabetes ranges from the antagonism of several neurotransmitter receptors to insulin resistance. A total of thirty-five cases of induced or exacerbated diabetes are presently available in the published literature; the vast majority of cases implicate clozapine (n=20) and olanzapine (n=15). In multiple cases, diabetic ketoacidosis has been the presenting symptom; daily atypical antipsychotic doses have been within acceptable ranges and were not considered to be excessive.
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PMID:New onset diabetes and atypical antipsychotics. 1122 9

The TaqIA D2 dopamine receptor (DRD2) minor (A1) allele was first associated with severe alcoholism a decade ago. Since then, studies both confirming and not confirmnning this finding were reported. However, a meta-analysis of a large number of Caucasian alcoholics (both more severe and less severe) and controls (both assessed and unassessed for substance use disorders) revealed a significantly higher frequency (p < 10(-6)) and prevalence (p < 10(-8)) of the DRD2 A1 allele in the alcoholics. Further analysis showed that the more severe alcoholics had a 3-fold higher prevalence of the DRD2 A1 allele than the assessed controls (p < 10(-10)), whereas no difference was found between the less severe alcoholics and the unassessed controls. DRD2 exonic or promoter mutations have not yet been associated with alcoholism, although two intronic variants at the TaqIB and intron 6 sites, which are in linkage disequilibrium with the TaqIA site, were associated with this disorder. Variants of the DRD2 gene have also been associated with cocaine, nicotine and opioid dependence, obesity and gambling. It is hypothesised that the DRD2 is a reinforcement or reward gene. Although less intensively studied than substance use disorders, the DRD2 gene has been implicated in Tourette's syndrome (TS), post-traumatic stress disorder (PTSD) and certain symptoms associated with affective disorders and schizophrenia. Further, DRD2 variants have been implicated in Parkinson's disease (PD) and in iatrogenically-induced movement disorders, as well as in certain migraineurs. Phenotypic differences have been associated with DRD2 variants. These include reduced D2 dopamine receptor numbers and diminished glucose metabolism in the brain of subjects who carry the DRD2 A1 allele. In addition, phenotypic differences have been found in neurocognitive and personality characteristics, and in treatment outcome of DRD2 variants. The involvement of the DRD2 gene in certain neuropsychiatric disorders opens up the potential of a targeted pharmacogenomic approach to the prevention and treatment of these disorders.
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PMID:The DRD2 gene in psychiatric and neurological disorders and its phenotypes. 1125 81

Positron emission tomography with uptake of [(18)F]fluorodeoxyglucose (FDG) and quantitative EEG were simultaneously performed in 18 medication-free patients with schizophrenia and in 13 normal volunteers. Subjects performed the Continuous Performance Task (CPT) during FDG uptake. Correlations were calculated between alpha power during the CPT and glucose metabolic rate (GMR) in thalamic regions and between alpha power during the CPT and GMR in occipital cortices. Regression analyses were used to describe the prediction of GMR in the occipital cortices and in the thalamic regions of occipital alpha power. In normal controls, we found (1) significant negative correlations between absolute alpha power and GMR in the left occipital cortex, (2) significant positive correlations between normalized alpha power and GMR in the right and left lateral thalamus and (3) combined effects of GMR in the thalamic regions and the occipital cortices on alpha power, which accounted for 98% of the variance of alpha power. In patients with schizophrenia, we found no significant correlations between alpha power and GMR in the occipital cortices or between alpha power and GMR in the thalamic regions. Correlation coefficients between absolute alpha power and GMR in the left occipital cortex and between normalized alpha power and GMR in the left lateral thalamus were significantly different in normal subjects compared to schizophrenic patients. The present findings provide evidence for involvement of the thalamus in the generation of alpha rhythm in humans. Furthermore, the present results suggest differences in thalamocortical circuits between normal controls and schizophrenic subjects.
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PMID:Eeg alpha rhythm and glucose metabolic rate in the thalamus in schizophrenia. 1134 Mar 67

The available literature suggests that patients with schizophrenia are at risk for diabetes mellitus and taking antipsychotic medication further increases the chance of developing non-insulin-dependent hyperglycemia. Case reports, chart reviews, and some results from clinical drug trials implicate a relationship between glucose levels and treatment with clozapine or olanzapine in patients with schizophrenia, although a few cases of hyperglycemia have also been reported in patients taking risperidone and quetiapine. These studies indicate that hyperglycemia is not dose dependent, is reversible on cessation of treatment with clozapine or olanzapine, and reappears on reintroduction of these therapies. The postulated underlying mechanisms involved in this process in patients with schizophrenia include (1) a decreased sensitivity to insulin that is independent of atypical medication, (2) an increased insulin resistance related to atypical medications, (3) the effects of atypical medications on serotonin receptors, and (4) overuse of insulin due to weight gain. These mechanisms are discussed in detail, and recommendations for the administration of atypical antipsychotics are offered. Overweight, ethnicity, family or personal history of diabetes mellitus or hypertension, and weight gain during the course of treatment have all been identified as risk factors in the development of hyperglycemia in patients with schizophrenia. However, it is difficult to statistically assess the true incidence of diabetes within each type of antipsychotic medication group with the exclusive dependence on available case studies and without proper epidemiologic research.
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PMID:Hyperglycemia associated with the use of atypical antipsychotics. 1160 83

Olanzapine has been associated with insulin resistance and new-onset diabetes mellitus. A 27-year-old African-American man developed new-onset severe hyperglycemia-glucose 1240 mg/dl, with ketonuria and acidosis, but no weight gain-2 years after starting olanzapine. Although his diabetes was stabilized with insulin, his family had difficulty monitoring his therapy, and insulin was discontinued. Subsequent monotherapy with pioglitazone stabilized the patient's glucose levels, allowing him to continue taking olanzapine. Health care professionals should be aware of links between olanzapine and diabetes mellitus and of the potential for delayed recognition of complications associated with diabetes in patients who are psychotic. Insulin poses additional problems because families of patients with schizophrenia have to deal with compliance and risk of accidental or suicidal overdose. This case and others described in the literature illustrate such dilemmas and highlight the need to further study links connecting diabetes, insulin resistance, and olanzapine. Further research to determine proportionality and risk differences among various atypical antipsychotics also is warranted.
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PMID:Olanzapine-associated severe hyperglycemia, ketonuria, and acidosis: case report and review of literature. 1171 20

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


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