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)

Patients with schizophrenia are at increased risk for developing the metabolic syndrome or its individual components due to their lifestyle, suspected genetic predisposition, and exposure to antipsychotic medications that can cause weight gain and other metabolic side effects. Despite the availability of clinical guidelines, screening for and monitoring of metabolic problems in this patient population continue to be suboptimal. We provide an overview specifically addressing 1) why patients with schizophrenia are at increased risk for metabolic problems; 2) how commonly used antipsychotic medications vary in terms of their metabolic liability; 3) how to effectively screen for and monitor metabolic problems in patients receiving antipsychotic medications; 4) what interventions can prevent, limit, or reverse the metabolic side effects of antipsychotic drug treatment; and 5) what are the barriers to the care of these patients.
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PMID:Metabolic syndrome associated with schizophrenia and atypical antipsychotics. 2042 84

Most studies point to an increased prevalence of metabolic syndrome (MS) and an increased risk of coronary heart disease (CHD) in schizophrenia patients with MS. The aims of this study were to compare the prevalence of MS in schizophrenia patients with the general population, to explore the clinical correlates and predictors of MS and to evaluate the risk for CHD within 10 years. Consecutive 319 patients, aged 18-75 years, with a diagnosis of schizophrenia according to the DSM-IV were enrolled. The ATP-III, the ATP-IIIA and the IDF criteria were used to define MS. 10-year risk of CHD events was calculated with the Framingham score. One hundred nine (34.2%) patients met the ATP-III criteria, 118 (37%) the ATP-IIIA and 133 (41.7%) the IDF criteria for MS. Patients with MS were older, had a later onset of illness and an older age at first hospitalization. The prevalence of MS in schizophrenia patients was higher from the general population only within the 20-29 age group. Patients with MS had a higher age and sex-corrected 10-year risk of CHD events. The only predictor of MS was the age of illness onset. In conclusion, countries where the general population prevalence of MS is already too high, schizophrenia patients younger than 30 years of age might be under higher risk of morbidity and mortality related with MS. This study points to the necessity for aggressive interventions to correct MS in schizophrenia as early as possible, within the first 10 years of post detection.
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PMID:The prevalence and clinical correlates of metabolic syndrome in patients with schizophrenia: findings from a cohort in Turkey. 2051 98

Most second-generation antipsychotics (SGAs) induce metabolic disturbances, but large differences exist in the degree to which individual patients develop these. Little is known about genetic factors associated with differential liability. Cross-sectional studies suggested an association between polymorphisms in 5,10-methylenetetraydrofolate reductase (MTHFR) and metabolic syndrome in patients with schizophrenia. This study aimed to assess whether the C677T (rs1801133) or A1298C (rs1801131) polymorphism in the MTHFR gene predict differential evolution of metabolic parameters over the course of a 3-month follow-up period after initiation of an SGA. One hundred and four patients with schizophrenia initiated on a SGA were measured at baseline, 6 weeks and 3 months. MTHFR A1298C, but not C677T, genotype predicted pos-baseline increases in weight [beta=2.5, standard error (SE)=0.92, P=0.006], waist circumference (beta=2.0, SE=1.0, P=0.050), fasting glucose (beta=2.8, SE=1.2, P=0.024) and glucose at 120 min during the Oral Glucose Tolerance Test (beta=10.7, SE=4.5, P=0.018) following a de novo metabolic challenge with a specific SGA. A1298C allele carriers consistently displayed the most unfavorable evolution of metabolic parameters. Thus, MTHFR A1298C genotype may explain part of the individual liability to metabolic disturbances in patients with schizophrenia.
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PMID:MTHFR genotype and differential evolution of metabolic parameters after initiation of a second generation antipsychotic: an observational study. 2052 22

Metabolic syndrome can contribute to significant morbidity and premature mortality and should be accounted for in the treatment of mental disorders. Patients with schizophrenia are at risk of undetected somatic comorbidity. Patients with schizophrenia have metabolically unfavorable body composition, comprising abdominal obesity, high fat percentage and low muscle mass, leading to increased risk of metabolic and cardiovascular diseases. Smoking, poor diet, reduced physical activity and alcohol or drug abuse are prevalent in people with schizophrenia and contribute to the overall cardiovascular disease risk. Side effects of antipsychotics may cause diagnostic problems in deciding regarding the origin of particular symptoms (somatic illness vs. side effects) during treatment of psychotic disorders. Bearing in mind frequent comorbidity between of psychotic and somatic disorders, early recognition of such comorbidity is important, as well as the selection of antipsychotics. The aim of this article is to report a case of changes in values of cholesterol and tryglicerides after weight loss, during treatment with aripiprazole in a patient with schizophrenia. This case report emphasizes the importance of regular monitoring of values of cholesterol and tryglicerides during treatment with antipsychotics.
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PMID:Changes in values of cholesterol and tryglicerides after weight loss during treatment with aripiprazole in a patient with schizophrenia - Case report. 2056 87

Second-generation antipsychotics are widely used in the treatment of all forms of psychoses, but they often produce undesirable side effects, among which are weight gain and other elements of metabolic syndrome. The mechanisms of these adverse effects are not known. The liver and adipose tissue are the principal candidate organs implicated in the development of antipsychotic-induced metabolic adverse effects. The present study investigated in the rat the effects on liver and white adipose tissue of a chronic treatment (46 days) with olanzapine 2 mg/kg or haloperidol 1 mg/kg, as compared with a control solution. In the liver, the expression of key genes involved in glucose transport and lipid metabolism and of regulatory transcription factors, as well as the TNFalpha gene, was not altered in response to either antipsychotic. Similarly, key genes involved in glucose transport and lipid metabolism were not changed in adipose tissue. However, the white adipose tissue was inflammatory in olanzapine-treated rats, with extensive macrophage infiltration and a significant increase in TNFalpha expression. In the plasma, TNFalpha and IL-1beta concentrations were slightly elevated. Chronic olanzapine treatment therefore produces a low-grade inflammatory state, likely initiated in the adipose tissue. Such an inflammatory state is known to be associated with an increased risk of insulin-resistance and cardiovascular diseases. This antipsychotic-induced inflammatory syndrome may participate in the inflammatory syndrome often observed in patients with schizophrenia. The strong and rather selective effect of olanzapine on TNFalpha expression may open new therapeutic opportunities for the prevention of olanzapine-induced metabolic abnormalities.
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PMID:Olanzapine-induced accumulation of adipose tissue is associated with an inflammatory state. 2057 Jun 65

When managing their patients with schizophrenia, psychiatrists are increasingly concerned about physical disorders, including weight gain, obesity, metabolic abnormalities (in particular, diabetes and the metabolic syndrome), prolactin increase, sexual dysfunction and cardiovascular disease. Other common health-related problems in these patients include recreational drug use, sedation/physical inactivity, adverse drug effects and poor self-care. Each of these can have an impact on patient well-being, adherence to therapy and life expectancy. Collectively they can pose substantial barriers to optimal outcomes. However, the widespread acknowledgement of the importance of the physical health of patients with schizophrenia does not always result in consistent monitoring and management of physical health risks in the clinic. Urgent action is needed to ensure that psychiatrists prioritise physical healthcare alongside mental healthcare as a way to improve the longterm outcomes of treatment in all patients with schizophrenia.
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PMID:The need for routine physical health care in schizophrenia. 2062 Aug 84

This international meeting discussed the management of physical health in patients with schizophrenia in several countries including France, Spain, Germany, the UK and Italy. Physical health parameters, including weight, blood pressure, blood glucose, lipids and standard biochemical assessments are measured in many patients at the first hospital consultation. These reveal physical disorders such as obesity, hypertension, dyslipidaemia, the metabolic syndrome, substance abuse, cardiovascular disease, extrapyramidal symptoms, sexual dysfunction and diabetes in substantial proportions of patients. Psychiatrists consider switching antipsychotic therapy if excessive sedation, extrapyramidal symptoms, unacceptable weight gain, hyperglycaemia or dyslipidaemia occur. In general, switching is more likely to be considered for symptomatic adverse events than for laboratory abnormalities. Switching is discouraged by limited knowledge of protocols, the absence of guidelines and fears of relapse or reduced treatment adherence. The physical health of patients with schizophrenia receives much less attention in the community setting than in the hospital setting. Improved guidelines, protocols, resources and support are needed to improve the physical health of patients in the community.
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PMID:Management of physical health in patients with schizophrenia: international insights. 2062 Aug 86

In the management of schizophrenia, mental health outcomes are the principal focus of treatment. The objective is to control the psychotic symptoms while minimising negative features of the illness, to achieve an overall improvement in the societal functioning of patients. Physical health is also important because if it is compromised, many of the benefits of improved mental health will be offset. Compared with the general population, schizophrenia patients are at increased risk of weight gain, abdominal obesity, diabetes, metabolic syndrome, and cardiovascular disease. These physical health problems can contribute to the decreased quality of life, lowered self-esteem and reduced life expectancy commonly reported in schizophrenia. For these reasons there is a pressing need to improve both the monitoring and the management of physical health in patients with schizophrenia as a part of their overall care. A consensus for metabolic monitoring of patients receiving treatment with antipsychotic drugs is available. However, the practicing clinician requires guidance about management of physical health in routine clinical practice. This should include recommendations for measurements that have strong predictive value about physical health risks yet are easy to make, and about the use of medications that have the least effect on physical health parameters. This article will review the gravity of the physical health risks facing schizophrenia patients.
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PMID:Physical health in schizophrenia: a challenge for antipsychotic therapy. 2062 Aug 88

Cardiovascular disease, metabolic syndrome, schizophrenia, diabetes, bipolar disorder, and autism are a few of the numerous complex diseases for which researchers are trying to decipher the genetic composition. One interest of geneticists is to determine the quantitative trait loci (QTLs) that underlie the genetic portion of these diseases and their risk factors. The difficulty for researchers is that the QTLs underlying these diseases are likely to have small to medium effects which will necessitate having large studies in order to have adequate power. Combining information across multiple studies provides a way for researchers to potentially increase power while making the most of existing studies.Here, we will explore some of the methods that are currently being used by geneticists to combine information across multiple genome-wide linkage studies. There are two main types of meta-analyses: (1) those that yield a measure of significance, such as Fisher's p-value method along with its extensions/modifications and the genome search meta-analysis (GSMA) method, and (2) those that yield a measure of a common effect size and the corresponding standard error, such as model-based methods and Bayesian methods. Some of these methods allow for the assessment of heterogeneity. This chapter will conclude with a recommendation for usage.
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PMID:Methods for combining multiple genome-wide linkage studies. 2065 21

In two previous studies we found an association between HTR2C polymorphisms and the prevalence of the metabolic syndrome in patients using antipsychotics. In this study, we set out to replicate our findings in a third separate sample of patients. Data for this cross-sectional study came from the ongoing Pharmacotherapy Monitoring and Outcome survey study, investigating the association between schizophrenia and metabolic or cardiovascular risk factors. Primary end point was the prevalence of the metabolic syndrome. Primary determinants were two polymorphisms in the HTR2C gene: rs3813929 (-759 C/T) and rs1414334:C>G. Carriership of the variant rs1414334 C-allele was significantly associated with an increase prevalence of the metabolic syndrome (odds ratio (OR) 3.73; 95% confidence interval (CI) 1.29-10.79, P=0.015). No association was found between the HTR2C -759 C/T polymorphism and the metabolic syndrome. This study confirms previous findings that the variant C-allele of the rs1414334 polymorphism is associated with the metabolic syndrome.
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PMID:Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics: a replication study. 2068 28


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