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.
"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. "
[Show abstract][Hide abstract] 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.
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.
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).
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.
Schizophrenia Research 10/2014; 159(1). DOI:10.1016/j.schres.2014.07.029 · 3.92 Impact Factor
[Show abstract][Hide abstract] 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.
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.
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.
Current opinion in psychiatry 03/2013; 26(2):144-150. DOI:10.1097/YCO.0b013e32835dc9da · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Clozapine is quite effective to treat schizophrenia, but its use is complicated by several factors. Although many patients respond to antipsychotic therapy, about 50% of them exhibit inadequate response, and ineffective medication trials may entail weeks of unremitted illness, potential adverse drug reactions, and treatment nonadherence. This review of the literature sought to describe the main pharmacogenetic studies of clozapine and the genes that potentially influence response to treatment with this medication in schizophrenics.
We searched the PubMed database for studies published in English in the last 20 years using keywords related to the topic.
Results and conclusions:
Our search yielded 145 studies that met the search and selection criteria. Of these, 21 review articles were excluded. The 124 studies included for analysis showed controversial results. Therefore, efforts to identify key gene mechanisms that will be useful in predicting clozapine response and side effects have not been fully successful. Further studies with new analysis approaches and larger sample sizes are still required.
Revista Brasileira de Psiquiatria 09/2013; 35(3):305-17. DOI:10.1590/1516-4446-2012-0970 · 1.77 Impact Factor
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