DRD4 48 bp VNTR but not 5-HT2C Cys23Ser receptor polymorphism is related to antipsychotic-induced weight gain

Abstract

Weight gain is a major side effect of antipsychotic treatment. The antidopaminergic and antiserotonergic effect of antipsychotics may contribute to antipsychotic-induced weight gain. We, therefore conducted a prospective clinical study, to investigate whether the D4 receptor (DRD4) 48 bp (base pair) variable number of tandem repeat (VNTR) polymorphism and the 5-hydroxytryptamine 2C receptor (HT 2C ) cysteine for serine substitution at position 23 (Cys23Ser) polymorphism may influence weight gain during antipsychotic treatment in a naturalistic setting of 102 Caucasian psychiatric in-patients. Patients suffering from psychotic disorders and treated according to local clinical practice were classified as either homozygous for the shorter alleles of the DRD4 48 bp VNTR polymorphism (o7-fold repeat, group 1) or heterozygous/homozygous for the long allele (7-fold repeat or higher, group 2). HT 2C Cys23Ser polymorphism male patients were grouped hemizygous G (Cys) or C (Ser), while female patients were GG, GC or CC and both sexes were evaluated separately. Concerning the DRD4 48 bp VNTR polymorphism the increase in body mass index was significantly less in group 1 (0.38 kg m À2 ; s.d. ¼ 1.04) than in group 2 (0.89 kg m À2 ; s.d. ¼ 1.23; P ¼ 0.003). The difference between the genotype groups remained significant in male patients but not in female patients. In contrast, no influence on antipsychotic-induced increase in body weight was observed for the HT 2C Cys23Ser polymorphism. These results support the hypothesis that the DRD4 48 bp VNTR polymorphism influences antipsychotic-induced weight gain. Male patients may be more affected than female patients. Due to the limitations of the study (heterogeneity of treatment, pretreatment and concomitant therapy) further studies are required before diagnostic genotyping of the DRD4 48 bp VNTR polymorphism may be useful for individualizing therapy.

Association Study of Brain-Derived Neurotrophic Factor Gene Polymorphisms and Body Weight Change in Schizophrenic Patients Under Long-Term Atypical Antipsychotic Treatment

“…In the following studies, several genetic variants have been reported to be associated with BWG during AAP treatment, such as genetic variants in HTR2C, HTR2A, HTR6, DRD4, GNB3, INSIG2, BDNF, LEP, SNP25, and ADRA2A (Reynolds et al 2002;Wang et al 2005;Ujike et al 2008;Le Hellard et al 2009;Lane et al 2006;Popp et al 2009;Calarge et al 2009;Müller et al 2005;Sickert et al 2009); however, replication in larger, independent samples is required to confirm these findings.…”

Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome

“…Candidate gene studies have produced significant findings in the 5-HTR2C, GNB3, ADR2A and DRD4 receptors. 10,46 Weight gain under olanzapine therapy was significantly lower for 5-HTR2C À759T-allele carriers (0.9 vs 3.9% for others within 4 weeks, P ¼ 0.011). This is in accordance with the results of several previous studies, which have shown a significant influence of this polymorphism on weight gain under olanzapine therapy.…”

Meta-Analysis of the Efficacy of Adjunctive NMDA Receptor Modulators in Chronic Schizophrenia

“…[17,21,33,34,36,54,55,58, Of these, 11 articles tested the hypothesis that ketamine worsens the symptoms of schizophrenia [21,55,92,93,103,106,109,125,127,131,150] and these were excluded from the analysis. Thirty-three publications without placebo comparisons, [33,34,36,78,79,82,90,91,94,101,110,112,[120][121][122]126,136,138,139,[141][142][143]146,[151][152][153][156][157][158][159][160]…”