Psychiatric Hospital Meerkanten

Ermelo, Netherlands

Psychiatric Hospital Meerkanten

Ermelo, Netherlands

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Gregoor J.G.,Psychiatric Hospital Meerkanten | Gregoor J.G.,University Utrecht | Mulder H.,University Utrecht | Mulder H.,Wilhelmina Hospital Assen | And 5 more authors.
Journal of Clinical Psychopharmacology | Year: 2010

Obesity is one of the most serious common somatic adverse effects of atypical antipsychotic agents. Genetic factors partly determine the individual patient's risk of developing obesity during treatment. As weight-regulating mechanisms, such as the leptinergic and serotonergic system, may be interdependent, genetic polymorphisms in these systems also may show interactions. To determine whether combined HTR2C-LEP genotype or HTR2C-LEPR genotype are associated with obesity in patients using atypical antipsychotic drugs, a cross-sectional study design was used. The study population included 200 patients aged between 18 and 65 years of age, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. Primary outcome measure was presence of obesity (body mass index, >30). Determinants were the combined (HTR2C -759C/T-LEPR Q223R), (HTR2C -759C/T-LEP -2548G/A, (HTR2C rs1414334-LEPR Q223R) and (HTR2C rs1414334-LEP -2548G/A) genotypes. Of the 200 included patients, 61 (31%) were obese. In patients without the HTR2C -759T allele, presence of the LEP -2548G allele was associated with obesity (odds ratio, 2.88; 95% confidence interval, 1.05-7.95). The results of the other analyses showed some nonsignificant trends. The combined (HTR2C -759C/T-LEP -2548G/A) genotype may be a determinant of obesity in patients during treatment with atypical antipsychotic drugs. © 2010 by Lippincott Williams & Wilkins.


Gregoor J.G.,Psychiatric Hospital Meerkanten | Gregoor J.G.,University Utrecht | Weide J.V.D.,Psychiatric Hospital Meerkanten | Van Megen H.J.,Psychiatric Hospital Meerkanten | And 2 more authors.
Pharmacogenomics | Year: 2011

Weight gain is a frequently occurring serious somatic adverse effect of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. Objectives: To determine whether LEPR Q223R, LEP -2548G/A and HTR2C -759C/T polymorphisms are associated with obesity and weight change in patients using atypical antipsychotic drugs. Methods: A longitudinal study design was used in a naturalistic setting. The study population included 141 patients, all of whom were using an atypical antipsychotic drug. The body mass index was measured twice. Primary outcome measures were obesity at the moment of first measurement and body mass index change during treatment. Determinants were the LEPR Q223R (rs1137101), the LEP -2548G/A SNP (rs7799039) and the HTR2C -759C/T (rs3813929) polymorphisms. Results: Of the 141 included patients, 35 (24.8%) were obese. In females, presence of the LEPR 223R allele was associated with an increased risk of obesity (47.6 vs 17.6%; p = 0.03). In males this association was not found. None of the SNPs were significantly associated with weight change during treatment. Conclusions: The LEPR Q223R polymorphism may be a risk factor for obesity in women with a psychotic disorder treated with atypical antipsychotic drugs. This is in line with earlier findings of our group. © 2011 Future Medicine Ltd.


De Vos A.,St Jansdal Hospital | Van Der Weide J.,St Jansdal Hospital | Van Der Weide J.,Psychiatric Hospital Meerkanten | Loovers H.M.,St Jansdal Hospital | Loovers H.M.,Psychiatric Hospital Meerkanten
Pharmacogenomics Journal | Year: 2011

Polymorphisms in genes coding for drug metabolizing enzymes, such as the cytochrome P450 enzymes CYP2C19 and CYP2D6, can lead to therapy failure and side effects. In earlier studies, the novel variant CYP2C1917 increased metabolism of several CYP2C19 substrates. The objective of this study was to evaluate the impact of CYP2C1917 on the metabolism of amitriptyline (AT), citalopram (CIT), and clomipramine (CLOM). Six-hundred and seventy-eight patients were included in this study, based on availability of DNA and serum levels of parent drug and main metabolite. We investigated the relationship between CYP2C19 genotypes and metabolic parameters, including serum levels corrected for dose and metabolic ratio (MR). The CYP2C1917 allele was significantly associated with decreased MR for CIT (CYP2C191/17 mean MR2.3, compared with CYP2C191/1 mean MR2.8) and AT (CYP2C1917/17 mean MR0.8, compared with CYP2C191/1 mean MR3.7 in the CYP2D61/1 subgroup). Furthermore, significant association of CYP2D6 genotype with AT, CIT, and CLOM metabolism was observed. No clear correlation was found between CYP2C19 genotype and CLOM metabolism. This study confirms the increased activity of the CYP2C1917 allele and shows increased metabolism of drugs that are metabolized by CYP2C19, including AT and CIT. However, the clinical relevance of CYP2C1917 is probably limited for AT, CIT, and CLOM. © 2011 Micmillan Publishers Limited. All rights reserved.


Gregoor J.G.,Psychiatric Hospital Meerkanten | Gregoor J.G.,University Utrecht | Van Der Weide J.,Psychiatric Hospital Meerkanten | Van Der Weide J.,St Jansdal Hospital | And 4 more authors.
Psychiatric Genetics | Year: 2010

BACKGROUND: Treatment with atypical antipsychotic agents is often complicated by dyslipidemia, which is a risk factor for cardiovascular disease. ObjectiveS: To determine whether the LEPR Q223R, the LEP-2548G/A, and the HTR2C-759C/T polymorphisms are associated with dyslipidemia in patients using atypical antipsychotic drugs. Methods: A cross-sectional study design was used. The study population included all patients who had been screened for dyslipidemia between January 2008 and March 2009 and had been using an atypical antipsychotic for at least 3 months at the moment of screening. Primary outcome measure was the mean total cholesterol (TC)/HDL ratio. Determinants were the LEPR Q223R (rs1137101), the LEP-2548G/A SNP (rs7799039), and the HTR2C-759C/T (rs3813929) polymorphisms. Results: A total of 353 patients was included in the study, of which 184 (52.1%) were men and 169 (47.9%) were women. Overall, no significant differences were found between the different genotype groups. However, in patients with a first admission to the hospital less than a year ago, the LEP-2548G allele had a lower mean TC/HDL ratio compared with patients without the LEP-2548G allele (6.41 vs. 4.12, P-adj: 0.017) and patients with the LEPR 223R allele had a lower mean TC/HDL ratio compared with patients without the LEPR 223R allele (5.04 vs. 3.92, P-adj: 0.019). The association between the LEP-2548G/A allele and the TC/HDL ratio in recent patients was present only in men. Conclusion: Genetic variation in the LEP and LEPR gene may be associated with short-term dyslipidemia in patients using atypical antipsychotic agents. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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