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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is one of the most common physical health problems among patients with severe and persistent mental illnesses, such as schizophrenia. Multifactorial in origin, obesity can be attributed to an unhealthy lifestyle as well as the effects of psychotropic medications such as second-generation antipsychotics. Excess body weight increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, hypertension, and gallbladder disease. A PubMed search revealed 403 English-language citations to the query "schizophrenia" AND "obesity" and 469 citations to the query "obesity" AND "antipsychotics." The evidence is that different antipsychotics have different propensities for weight gain, and that children, adolescents, and fi rst-episode patients are at higher risk for weight gain associated with antipsychotic treatment. Monitoring body weight early in treatment will help predict those at high risk for substantial weight gain. Switching antipsychotic medication may or may not be clinically feasible, but can lead to a reduction in body weight. Lifestyle therapies and other nonpharmacological interventions have been shown to be effective in controlled clinical trials, but the evidence base for adjunctive medication strategies such as with orlistat, sibutramine, amantadine, nizatidine, metformin, topiramate, and others, is conflicting. At the very least, a "small-steps approach" to managing weight should be offered to all patients who are overweight or obese.
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PMID:Schizophrenia, obesity, and antipsychotic medications: what can we do? 1865 65

Schizophrenia is associated with an increased risk of metabolic disorders such as diabetes, dyslipidaemia and the metabolic syndrome. The prevalence of type 2 diabetes in schizophrenic patients is at least twice that of the general population. Around 40 percent of patients meet criteria for the metabolic syndrome. Recently there is a growing concern on the metabolic side effects of treatment with second generation antipsychotics. According to various studies, including a prospective study performed in Flanders, treatment with clozapine and olanzapine has the highest metabolic risk, followed by quetiapine and risperidone. Amisulpride, ziprasidone and aripiprazole appear to have a low metabolic risk. Appropriate care, taking into account the possible improvement of the metabolic risks factors, is important to reduce morbidity and mortality in schizophrenic patients treated with antipsychotic medications.
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PMID:[Brain in the core of metabolic regulations: disorders in schizophrenic patients treated with atypical antipsychotics]. 1866 14

Individuals with schizophrenia are at increased risk for poor health outcomes and mortality. This may be due to inadequate self-management of co-occurring conditions, such as type 2 diabetes. We compared adherence to oral hypoglycemic medications for diabetes patients with vs without comorbid schizophrenia. Using Veterans Affairs (VA) health system administrative data, we identified all patients with both schizophrenia and type 2 diabetes and with at least one oral hypoglycemic prescription fill in fiscal year 2002 (N = 11 454) and a comparison group of patients with diabetes who were not diagnosed with schizophrenia (N = 10 560). Nonadherence was operationalized as having a medication possession ratio indicating receipt of less than 80% of needed hypoglycemic medications. Poor adherence was less prevalent among diabetes patients with (43%) than without schizophrenia (52%, P < .001). In multivariable analyses, having schizophrenia was associated with a 25% lower likelihood of poor adherence compared with not having schizophrenia (adjusted odds ratio: 0.75, 95% confidence interval: 0.70-0.80). Poorer adherence was associated with black race, homelessness, depression, substance use disorder, and medical comorbidity. Having more outpatient visits, a higher proportion of prescriptions delivered by mail, lower prescription copayments, and more complex medication regimens were each associated with increased adherence. Among veterans with diabetes receiving ongoing VA care, overall hypoglycemic medication adherence was low, but individuals with comorbid schizophrenia were more likely to be adherent to these medications. Future studies should investigate whether factors such as comanagement of a chronic psychiatric illness or regular contact with mental health providers bestow benefits for diabetes self-management in persons with schizophrenia.
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PMID:Does adherence to medications for type 2 diabetes differ between individuals with vs without schizophrenia? 1871 83

Atypical antipsychotics now represent the mainstay of treatment for patients with schizophrenia. Unfortunately, as a class they have also been associated with an increased risk of weight gain and metabolic abnormalities, including type 2 diabetes. We have investigated the diabetogenic effects of a spectrum of antipsychotics, both atypical and typical. Healthy animals were treated acutely with clozapine (10 mg/kg), olanzapine (3.0 mg/kg), risperidone (1 mg/kg), ziprasidone (3 mg/kg) or haloperidol (0.25 mg/kg) and tested using the hyperinsulinemic-euglycemic and hyperglycemic clamp procedures. Clozapine and olanzapine had a rapid and potent effect on insulin sensitivity by lowering the glucose infusion rate and increasing hepatic glucose production. Both clozapine and olanzapine, as well as risperidone, decreased peripheral glucose utilization. Neither ziprasidone nor haloperidol had a significant impact on insulin sensitivity. In the hyperglycemic clamp, clozapine and olanzapine impaired beta cell function as reflected by a decrease in insulin secretion. Results confirm that 1) antipsychotic medications have an immediate impact on metabolic parameters and 2) the various atypical antipsychotics differ in their propensity to acutely induce metabolic side effects. Our data also support the preclinical use of these clamp procedures in screening putative antipsychotics.
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PMID:Insulin resistance and secretion in vivo: effects of different antipsychotics in an animal model. 1915 85

The concept of fetal programming states that changes in the fetal environment during sensitive periods of organ development may cause long-lasting changes in the structure and functioning of these organs later in life and influence the risk for chronic diseases such as coronary heart disease and type 2 diabetes. Fetal growth is a summary marker of the fetal environment and is reflected by relatively easy-to-obtain measures of size at birth such as birth weight. In the last two decades, a body of evidence emerged linking fetal growth with behavioural and mental health outcomes later in life. Cognitive functioning and behavioural problems in childhood, in particular inattention/hyperactivity, have been shown to be inversely related to fetal growth. Although results are mixed, risk for personality disorders and schizophrenia seems to be linked with fetal growth and adversity, while the evidence for mood disorders is weak. Vulnerability for psychopathology may also be influenced by prenatal adversity. There is evidence for associations of fetal growth with temperament in childhood as well as stress reactivity and distress. The associations of fetal growth with mental health later in life are potentially caused by specific prenatal factors such as maternal smoking, alcohol, toxins/drugs, nutrition, psychosocial stress and infection during pregnancy. The mechanisms likely involve changes in neurodevelopment and in the set point of neuroendocrine systems, and there is evidence that prenatal adversity interacts with genetic and postnatal environmental factors. Future studies should examine the effects of specific prenatal factors and attempt to disentangle genetic and prenatal environmental effects.
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PMID:Fetal origins of mental health: evidence and mechanisms. 1921 37

Olanzapine is a second-generation antipsychotic that may cause weight gain and metabolic syndrome in some cases. The peroxisome proliferator-activated receptor (PPAR)-gamma is an important gene in the progress of type II diabetes and metabolic syndrome. In recent studies the polymorphism of the PPAR-gamma has been studied in type II diabetes mellitus, polycystic ovary syndrome, and insulin resistance syndrome. It is aimed to evaluate the association between polymorphism of PPAR-gamma gene and olanzapine-induced weight gain. Our study comprised 95 unrelated subjects who strictly met Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for schizophrenia, and all were of Turkish origin. All patients were evaluated with rating scales, and genetic analyses were performed. We found statistically significant differences between pretreatment and posttreatment body mass index and weight change in Pro12Ala polymorphism of PPAR-gamma2. Our results suggest that genetic polymorphism of PPAR might be important in olanzapine-induced weight gain and that genetic variance of people might be considered in antipsychotic medication selection.
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PMID:The association of olanzapine-induced weight gain with peroxisome proliferator-activated receptor-gamma2 Pro12Ala polymorphism in patients with schizophrenia. 1962 37

An increased prevalence of type 2 diabetes (T2D) in schizophrenia (SCZ) patients has been observed. Exposure to antipsychotics (APs) has been shown to induce metabolic dysregulation in some patients but not all treated patients. We hypothesized that important candidate genes for T2D may increase risk for T2D in African-American patients with SCZ or schizoaffective disorder. The PAARTNERS study comprises African-American families with at least one proband with SCZ or schizoaffective disorder. The current study of PAARTNERS SCZ and schizoaffective disorder cases (N=820) examined single nucleotide polymorphisms (SNPs) within select T2D candidate genes including transcription factor 7-like 2 (TCF7L2), calpain 10 (CAPN10), and ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENNP1) for association with prevalent T2D. We report the association of TCF7L2 (rs7903146) with T2D under both additive and recessive models for the risk allele T. Specifically, the odds ratio (OR) for having T2D was 1.4 (p=0.03) under an additive model and 2.4 (p=0.004) under a recessive model. We also report a marginally significant TCF7L2 by AP treatment interaction that should be investigated in future studies. CAPN10 (rs3792267) was marginally associated with T2D with OR=1.5 (p=0.08) when considering the model GG vs. AG/AA with risk allele G. ENPP1 (rs1044498) was not associated with T2D. We conclude TCF7L2, a risk factor for T2D in the general population, is also a risk factor for T2D in African-American patients with SCZ or schizoaffective disorder. Research is needed to determine if T2D associated polymorphisms are of interest in the pharmacogenetics and future treatment choices of antipsychotics in African-American patients.
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PMID:Genetic risk factors for type 2 diabetes with pharmacologic intervention in African-American patients with schizophrenia or schizoaffective disorder. 1964 78

Interpretation of case reports of antipsychotic-associated diabetes mellitus is complicated by the high background risk for diabetes in those with chronic serious mental disorders and the high prevalence of asymptomatic undiagnosed diabetes in the general population. Controlled metabolic studies are needed to provide more definitive information concerning the types of metabolic effects that may be associated with the atypical antipsychotics. Therefore, this article reviews what has been learned from metabolic studies concerning the types of disturbances involved in the etiology of type 2 diabetes and presents findings from metabolic studies done with antipsychotics. Glucose tolerance studies involving both conventional and atypical antipsychotics are reviewed first. Findings from insulin sensitivity studies are then presented. These include clamp studies of the effects of atypical antipsychotics on insulin sensitivity and beta-cell function in both healthy subjects and patients with schizophrenia. Studies evaluating the effects of the atypical antipsychotics on insulin secretion are then reviewed. The article concludes with an evaluation of the evidence and suggestions for future research in this area.
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PMID:Metabolic studies of atypical antipsychotic agents and diabetes. 1966 54

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

Polyunsaturated fatty acids (PUFAs) form an important constituent of all the cell membranes in the body. PUFAs such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) form precursors to both pro-inflammatory and anti-inflammatory compounds. Low-grade systemic inflammation occurs in clinical conditions such as insulin resistance, hypertension, type 2 diabetes mellitus, atherosclerosis, coronary heart disease, lupus, schizophrenia, Alzheimer's disease, and other dementias, cancer and non-alcoholic fatty liver disease (NAFLD) that are also characterized by an alteration in the metabolism of essential fatty acids in the form of excess production of pro-inflammatory eicosanoids and possibly, decreased synthesis and release of anti-inflammatory lipoxins, resolvins, protectins and maresins. We propose that low-grade systemic inflammation observed in these clinical conditions is due to an imbalance in the metabolism of essential fatty acids that is more in favour of pro-inflammatory molecules. In this context, transgenic fat-1 mouse that is designed to convert n-6 to n-3 fatty acids could form an ideal model to study the altered metabolism of essential fatty acids in the above mentioned conditions. It is envisaged that low-grade systemic inflammatory conditions are much less likely in the fat-1 mouse and/or these diseases will run a relatively mild course. Identifying the anti-inflammatory compounds from n-3 fatty acids that suppress low-grade systemic inflammatory conditions and understanding their mechanism(s) of action may lead to newer therapeutic strategies.
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PMID:Transgenic fat-1 mouse as a model to study the pathophysiology of cardiovascular, neurological and psychiatric disorders. 2004 3


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