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)

Polyunsaturated fatty acids (PUFAs) are essential structural components of all cell membranes and, more so, of the central nervous system. Several studies revealed that n-3 PUFAs possess anti-inflammatory actions and are useful in the treatment of dyslipidemia. These actions explain the beneficial actions of n-3 PUFAs in the management of cardiovascular diseases, inflammatory conditions, neuronal dysfunction, and cancer. But, the exact molecular targets of these beneficial actions of n-3 PUFAs are not known. Mice engineered to carry a fat-1 gene from Caenorhabditis elegans add a double bond into an unsaturated fatty acid hydrocarbon chain and convert n-6 to n-3 fatty acids. This results in an abundance of n-3 eicosapentaenoic acid and docosapentaenoic acid specifically in the brain and a reduction in n-6 fatty acids of these mice that can be used to evaluate the actions of n-3 PUFAs. Gene expression profile, RT-PCR and protein microarray studies in the hippocampus and whole brain of wild-type and fat-1 transgenic mice revealed that genes and proteins concerned with inflammation, apoptosis, neurotransmission, and neuronal growth and synapse formation are specifically modulated in fat-1 mice. These results may explain as to why n-3 PUFAs are of benefit in the prevention and treatment of diseases such as Alzheimer's disease, schizophrenia and other diseases associated with neuronal dysfunction, low-grade systemic inflammatory conditions, and bronchial asthma. Based on these data, it is evident that n-3 PUFAs act to modulate specific genes and formation of their protein products and thus, bring about their various beneficial actions.
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PMID:Gene and protein expression profiling of the fat-1 mouse brain. 1913 87

Signal detection methods were used to identify values of metabolic variables that predict development of prediabetes or diabetes before (moderators) or associated with treatment (mediators), utilizing data from two multi-center clinical trials of patients with schizophrenia, treated for 6 months with olanzapine (OLZ) or ziprasidone (ZIP). At baseline, participants were often overweight/obese (63% with a body mass index >or=25.0kg/m(2)), dyslipidemic [more than one-third had elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations], and prediabetic (20%). Weight gain was significantly greater in OLZ-treated patients, as was accentuation of dyslipidemia. However, there were no significant correlations between weight gain and lipid changes from baseline to weeks 2, 4, 8 or to last observation. Type 2 diabetes developed in 4% and prediabetes in 18% of the population. Significant baseline predictors of diabetes were a HDL-C concentration <28mg/dL, or being >or=58-years-old if HDL-C concentration was >or=28mg/dL. Baseline plasma glucose concentration >or=92mg/dL was the only significant predictor of developing prediabetes, accounting for 60% of cases. Post-treatment increments in plasma TG concentrations >or=145mg/dL or >or=59mg/dL were significant predictors of diabetes (23%) or prediabetes (27%), respectively. If the increase in TG was <145mg/dL, rapid weight gain >or=6.1kg in 2 weeks predicted development of diabetes (18%). These findings provide a quantitative approach to identify those at greatest treatment-associated risk to develop glucose intolerance, and emphasize the need to address co-morbid medical disorders in these patients.
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PMID:In search of moderators and mediators of hyperglycemia with atypical antipsychotic treatment. 1926 68

Cross-sectional studies showed a high prevalence of metabolic syndrome in patients with schizophrenia.This study aimed to identify the incidence of metabolic syndrome and its reversal in a non-preselected cohort of chronic psychotic patients in routine practice in one year follow-up and to find variables to describe development and reversal of metabolic syndrome. This cohort study was conducted as part of a disease management program and patients were included if they had two complete assessments in a one year follow-up. We conducted two logistic regressions to find variables to describe the development of metabolic syndrome and the reversal of metabolic syndrome. At the time of the first assessment 35% (n=92) of the 260 included patients had metabolic syndrome. Within one year 21 patients developed metabolic syndrome and 30 patients had it reversed. This was an incidence of 13% (21/168) and a reversal of 33% (30/92). Smoking, family history of cardiovascular diseases, and duration of disease >6 years was associated with a higher risk of developing metabolic syndrome as well as abdominal obesity and dyslipidemia. Patients with abdominal obesity had a smaller chance of reversing metabolic syndrome. Other variables included in the logistic regression such as receiving cardiovascular/antidiabetic drug treatment or duration of disease >6 years did not alter the risk of reversing the metabolic syndrome. Our study showed that the natural course of metabolic syndrome is dynamic. A considerable number of patients developed or reversed the metabolic syndrome in one year follow-up.
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PMID:The incidence of metabolic syndrome and its reversal in a cohort of schizophrenic patients followed for one year. 1939 13

Patients with severe mental illnesses have a higher risk of premature mortality than the general US population. Illnesses such as schizophrenia and bipolar disorder are frequently complicated by physical comorbidities such as diabetes and cardiovascular disease, including both coronary heart disease and cerebrovascular disease, which are associated with increased mortality and morbidity. Coronary heart disease is the leading cause of death among individuals with severe mental illnesses. Modifiable risk factors such as dyslipidemia, hyperglycemia, hypertension, smoking, and obesity are common in this population and contribute to risk for both diabetes and coronary heart disease. While many psychotropic medications used in the treatment of schizophrenia or bipolar disorder have similar efficacy, some medications are associated with more metabolic side effects than others, and clinicians should consider these risks when choosing among these medications. Patients with severe mental illnesses tend to have reduced access to health care and treatment for medical comorbidities compared with the general population. Therefore, clinicians involved in the care of this patient population should screen and monitor carefully for cardiometabolic side effects and risk factors.
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PMID:Comparing the safety and efficacy of atypical antipsychotics in psychiatric patients with comorbid medical illnesses. 1957 Apr 99

It is a well known fact that mentally ill patients, especially those with schizophrenia, have a higher incidence of somatic diseases than the general population and finally a significantly shorter life expectancy. In this paper a comparison is made between schizophrenia and somatic comorbidity before the era of antipsychotics and after, with consideration to the prevalent morbidity during each of these periods. In the period before antipsychotics acute infectious diseases and TBC were the prevalent comorbid diseases. High comorbidity rates were due not only to epidemics but also poor treatment success, deficient health habits and poor personal hygiene. In the period after the discovery of antipsychotics significant changes in morbidity occurred with the prevalence of chronic degenerative diseases, primarily diabetes, hypertension and dyslipidemia. Studies show that new generation antipsychotics partly generate the occurrence of metabolic disorders, which makes it necessary to consider the choice of antipsychotic depending on the assessed risk in every individual case.
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PMID:Psychofarmacology in the prevention of somatic comorbid diseases in mentally ill patients. 1979 55

For patients with mental illness, the purpose of antipsychotic medication is to improve their quality of life, and for many, quality of life improves dramatically with treatment. However, weight gain in the range of 7 to 10% is commonly associated with the use of antipsychotic medications and can have a negative impact on patient quality of life. Being overweight or obese can lead to serious medical conditions, including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, arthritis and coronary heart disease. The physical and psychological consequences of weight gain are an added burden for patients with schizophrenia or other mental disorders. Successful strategies to prevent and manage weight gain include diet and exercise interventions and, in some cases, switching to a different antipsychotic agent.
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PMID:Quality of life issues associated with antipsychotic-induced weight gain. 1980 98

Diabetes mellitus is a chronic disease affecting approximately 6% of the general population. Depression and schizophrenia are often comorbid with diabetes. There are two main ways to explain this phenomenon. Firstly, patients with diabetes mellitus have higher incidence of psychiatric disorders and secondly, antidepressants and antipsychotics may cause metabolic abnormalities. Antidepressants with noradrenergic activity have the highest potential to cause metabolic abnormalities. In schizophrenia, the risk is highest with clozapine and olanzapine pose the highest risk, moderate for risperidone and quetiapine, while ziprasidone and sertindole have not been associated with diabetes. American Diabetes Association and American Psychiatric Association suggested that optimal management of patients with schizophrenia should include baseline assessment on their weight, waist circumference, blood pressure, blood glucose level and lipidogram and family history on obesity, diabetes, dyslipidemia, hypertension and cardiovascular illness. During the first three months, weight gain should be monitored on monthly basis, while biochemical analysis should be performed after the first three months, and then once a year. In patients with significant weight gain, increase of blood glucose level or dyslipidemia, the first intervention should be switch to another antipsychotic. If necessary, a patient should be referred to an endocrinologist and advised on changing their life style.
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PMID:The comorbidity of diabetes mellitus and psychiatric disorders. 1993 98

People with schizophrenia have an increased prevalence of overweight/obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome, which increases the risk for cardiovascular diseases and mortality. Part of this increased risk is attributable to the use of antipsychotic medications, especially second-generation antipsychotics. Antipsychotic drugs differ in their potential to induce weight gain, with clozapine and olanzapine exhibiting the highest weight gain liability; evidence for differing effects of antipsychotics on glucose and lipid metabolism is less convincing. Individuals with schizophrenia may develop hyperprolactinemia, with or without clinical symptoms, after starting antipsychotic medications. This effect is particularly frequent with first-generation antipsychotics and with the second-generation antipsychotic risperidone and paliperidone. Psychiatrists should be aware of metabolic and endocrine side effects of antipsychotics and should make every effort to prevent or minimize them to improve the patients' compliance and quality of life.
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PMID:Management of schizophrenia with obesity, metabolic, and endocrinological disorders. 1994 83

Atypical antipsychotic drugs have less extra pyramidal side effects and are more effective to control the clinical manifestations of schizophrenia. However, their use may be associated to a higher incidence of weight gain, dyslipidemia, metabolic syndrome, glucose intolerance and type 2 diabetes mellitus. We performed a systematic literature search to evaluate the risk of type 2 diabetes mellitus incidence associated to the use of atypical antipsychotic drugs, compared to conventional treatment. If users of all types of atypical antipsychotic drugs are compared with users of conventional treatment, no significant differences in the incidence of type 2 diabetes mellitus were observed. If individual drugs are evaluated, clozapine and risperidone are associated with a higher risk of diabetes than haloperidol. Quetiapine is associated with a lower risk of diabetes than conventional treatment. The quality of the evidence found was low; therefore, new studies should been performed.
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PMID:[Risk of type 2 diabetes mellitus among users of atypical antipsychotic drugs or conventional treatment: systematic review and meta-analysis]. 2009 98

Severe mental illnesses, such as schizophrenia and bipolar affective disorder, are associated with excess cardiovascular morbidity and mortality. Cardiovascular risk in psychiatric disorders is partly related to antipsychotic therapy, especially second-generation or atypical antipsychotics. Some antipsychotic medications are associated with proatherogenic conditions including insulin resistance and dyslipidemia. In particular, olanzapine and clozapine have been consistently demonstrated to promote insulin resistance and dyslipidemia. Ziprasidone and amisulpiride may be associated with more favorable metabolic effects. Many of the published data relating to metabolic effects of anti-psychotics originate from retrospective studies. However, prospective randomized-controlled data are emerging, and the latest evidence is described here.
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PMID:Effect of antipsychotic medications on glucose and lipid levels. 2041 Apr 51


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