TNF-α -308 G>A polymorphism and weight gain in patients with schizophrenia under long-term clozapine, risperidone or olanzapine treatment

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
Neuroscience Letters (Impact Factor: 2.03). 09/2011; 504(3):277-80. DOI: 10.1016/j.neulet.2011.09.046
Source: PubMed


Atypical or second-generation antipsychotics (SGAs) are associated with excessive body weight gain (BWG) and other components of metabolic syndrome. Among all SGAs, clozapine and olanzapine are known to cause the most significant weight gain, followed by risperidone and quetiapine. The genetic variant of tumor necrosis factor α (TNF-α), -308 G>A polymorphism (rs1800629), has been implicated in clozapine-induced BWG in several studies. We hypothesized that TNF-α -308 G>A polymorphism has a general effect on SGA-induced BWG. The present study was conducted to examine the association between TNF-α -308 G>A polymorphism and BWG during treatment for schizophrenia using a variety of second generation antipsychotics (SGAs). A total of 500 patients with schizophrenia treated with clozapine (n=275), olanzapine (n=79) or risperidone (n=146) for an average of 49.9 months were recruited. Subjects with an increase in weight of more than 7% from the baseline before the current SGA treatment to the weight at the survey point were defined as having BWG. The association between TNF-α -308 G>A polymorphism and BWG was studied, and the effect of non-genetic factors such as baseline BMI, SGA treatment duration and SGA type on the association was controlled by logistic regression. The results revealed that there was no significant association between BWG and TNF-α -308 G>A polymorphism (GG/GA/AA or GG/GA+AA) in each separate SGA group or collectively. These findings suggest that TNF-α -308 G>A polymorphism does not play a major role in SGA-induced weight gain.

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Available from: Ya Mei Bai, Nov 15, 2015
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    • "However, the role of atopy-related immunological dysregulation in the development of metabolic syndrome/ disorders among those with severe mental disorders has been rarely investigated. In the early 2000s, Basile et al. hypothesized that the genetic polymorphisms of some potential genes (i.e., serotonin receptor genes, histamine receptor genes, and TNF-α) were associated with weight gain and metabolic syndrome among patients with severe mental disorder (Basile et al., 2001), but later Huang et al. failed to find the association between the 308 G N A polymorphism of TNF-α and weight gain among patients with schizophrenia (Huang et al., 2011). In our study, we found that a predisposition for allergies was an independent risk factor in patients with schizophrenia or bipolar disorder that predicted subsequent hypertension, dyslipidemia, and diabetes mellitus, after adjusting for demographic data and psychiatric comorbidities, and further suggested a dose-dependent relationship between the greater number of atopic comorbidities and the greater likelihood of hypertension, dyslipidemia, and diabetes mellitus. "
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    ABSTRACT: Background Previous studies have shown that both severe mental disorders (schizophrenia and bipolar disorder) and atopic diseases were associated with an increased risk of metabolic syndrome. However, the role of atopy/the predisposition for allergies in the development of metabolic syndrome is still unknown among those with severe mental disorders. Methods Using the Taiwan National Health Insurance Research Database, 5826 patients with schizophrenia or bipolar disorder (1908 with a predisposition for allergies and 3918 without) were enrolled between 1998 and 2008. Those who developed hypertension, dyslipidemia, and/or diabetes mellitus were identified during the follow-up to the end of 2011. Results A predisposition for allergies increased the risk of developing hypertension (HR: 1.67), dyslipidemia (HR: 1.82), and diabetes mellitus (HR: 1.37) in later life among those with severe mental disorders. A dose-dependent relationship was noted between having more atopic comorbidities and a greater likelihood of hypertension (1 atopic disease: HR: 1.60; ≧ 2 atopic comorbidities: HR: 1.87), dyslipidemia (HR: 1.73; HR: 2.12), and diabetes mellitus (HR: 1.26; HR: 1.69). Conclusion A predisposition for allergies was an independent risk factor for hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder. Further studies would be required to elucidate the underlying pathophysiology among atopy, schizophrenia, bipolar disorder, and metabolic syndrome.
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    ABSTRACT: Clozapine is the best treatment option in several clinical circumstances, including treatment-resistant schizophrenia, non treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson's disease, prevention and treatment of tardive dyskinesia. However, clozapine is associated with many serious side effects. Furthermore, monitoring requirements, i.e., frequent blood draws and frequent visits, discourage clozapine use. Therefore, the drug is underused. The only way to avoid the underuse of clozapine is full awareness of its side effects and competence to minimize them. The aim of the paper is reviewing the safety profile of clozapine and the suggested strategies in the management of its side effects, including neutropenia, eosinophilia, seizures, myocarditis, weight gain, diabetes, metabolic syndrome, hypersalivation, fever, constipation, ileus, urinary incontinence, sweating. The neuropsychiatric side effects of clozapine are not discussed in this review.
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    ABSTRACT: Purpose of review: Antipsychotic drugs are effective in alleviating a variety of symptoms and are medication of first choice in schizophrenia. However, a substantial interindividual variability in side effects often requires a lengthy 'trial-and-error' approach until the right medication is found for the right patient. Genetic factors have long been hypothesized to be involved and identification of related gene variants could be used to predict and tailor drug treatment. Recent findings: This review highlighting the most recent genetic findings was conducted on the two most common and most well-studied side effects: antipsychotic-induced weight gain and tardive dyskinesia. Summary: Regarding weight gain, most promising and most consistent findings were obtained in the serotonergic system (HTR2C) and with hypothalamic leptin-melanocortin genes, in particular with one variant close to the melanocortin-4-receptor (MC4R) gene. With respect to tardive dyskinesia, most interesting findings were generally obtained in genes related to the dopaminergic system (dopamine receptors D2 and D3), and more recently with glutamatergic system genes. Overall, genetic studies have been successful in identifying strong findings, in particular for antipsychotic-induced weight gain and to some extent for tardive dyskinesia. Apart from the need for replication studies in larger and well-characterized samples, the next challenge will be to create predictive algorithms that can be used for clinical practice.
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