Addiction Rehab: Association of a Functional Polymorphism in Neuropeptide Y With Antipsychotic-Induced Weight Gain in Schizophrenia Patients.
Association of a Functional Polymorphism in Neuropeptide Y With Antipsychotic-Induced Weight Gain in Schizophrenia Patients.
Filed under: Addiction Rehab
J Clin Psychopharmacol. 2012 Dec 28;
Tiwari AK, Brandl EJ, Weber C, Likhodi O, Zai CC, Hahn MK, Lieberman JA, Meltzer HY, Kennedy JL, Müller DJ
ABSTRACT: Significant body weight gain (BWG) is a serious adverse effect of a number of antipsychotic drugs. Previous studies have demonstrated an influence of clozapine, but not haloperidol, on neuropeptide Y (NPY) expression in the hypothalamus. Because NPY is a potent orexigenic peptide stimulating food intake, and genetic variation of the gene has been shown to influence development of obesity, we investigated the impact of NPY polymorphisms on antipsychotic-induced BWG.We analyzed 5 polymorphisms in the NPY gene (rs10551063, rs16147, rs5573, rs5574, and rs16475) in schizophrenia subjects (n = 226), treated mostly with clozapine and olanzapine for up to 14 weeks. Association was tested using analysis of covariance with change (%) from baseline weight as the dependent variable and duration of treatment and baseline body weight as covariates.In patients of European ancestry who received either clozapine or olanzapine, significant genotypic and allelic association of rs16147 with weight change was observed (Pcorrected = 0.012 and 0.018, respectively). Carriers of the C allele gained significantly more weight compared with individuals with TT genotype (CC + CT vs TT; 5.82% ± 5.6% vs 2.25% ± 4.8%; P= 0.001). Similarly, 2 other polymorphisms (rs5573 and rs5574) were also significantly associated with weight change (Pcorrected = 0.018 and 0.03). In addition, we observed a significant gene-gene interaction between the rs16147 in NPY and rs806378 in cannabinoid receptor 1 (Pcorrected = 0.011).Our observation of association of NPY polymorphisms gives further evidence for a genetic influence on antipsychotic-induced BWG and suggests a role of NPY gene in influencing this complex adverse effect.
HubMed – addiction
PXR Polymorphisms Interacted With CYP2B6 Polymorphisms on Methadone Metabolites.
Filed under: Addiction Rehab
J Clin Psychopharmacol. 2012 Dec 28;
Tsai HJ, Wang SC, Tian JN, Chang TK, Ho IK, Hsiao CF, Chen CH, Tan HK, Lin L, Wu CS, Su LW, Huang CL, Yang YH, Liu ML, Lin KM, Liu YL
Association Between Antidepressants and Venous Thromboembolism in Taiwan.
Filed under: Addiction Rehab
J Clin Psychopharmacol. 2012 Dec 28;
Wu CS, Chang CM, Chen CY, Wu EC, Wu KY, Liang HY, Chao YL, Chung WS, Tsai HJ
OBJECTIVE: To investigate the association between venous thromboembolism (VTE) and antidepressant use in an Asian population. METHODS: The authors conducted a nested case-control study of 1888 patients with VTE and 11,222 matched controls enrolled in the National Health Insurance Research Database in Taiwan from 2001 to 2009. The antidepressant exposure status and potential confounding factors were measured and included in the analyses. Conditional logistic regressions were applied to determine the effect of antidepressant use on VTE. RESULTS: We found a significant association of current antidepressant use with VTE in the total study sample (adjusted odds ratio [aOR], 1.59; 95% confidence interval (CI), 1.27-2.00). With regard to antidepressant classes and potency, we found that tricyclic antidepressants (aOR, 1.56; 95% CI, 1.11-2.18), serotonin 5-HT2A receptor blockers (aOR, 2.03; 95% CI, 1.27-3.24), and antidepressants with a low potency of serotonin reuptake inhibition (aOR, 1.57; 95% CI, 1.18-2.08) were associated with a significantly increased risk of VTE. When further stratifying by age, sex, and comorbid conditions, the VTE risk with antidepressant use was elevated among young and middle-aged adults, but not among the elderly. In addition, an elevated risk of VTE was observed in women and subjects without severe comorbid conditions, but not in men and subjects with severe comorbid conditions. CONCLUSIONS: There was a small increase in VTE risk with antidepressant use. The prescription of antidepressant drugs should be cautious, and especially, should be based on clinical evaluations of benefits and risks. The underlying mechanisms of the interaction between antidepressants and VTE warrant further investigation.
HubMed – addiction
Copy number variation findings among 50 children and adolescents with autism spectrum disorder.
Filed under: Addiction Rehab
Psychiatr Genet. 2012 Dec 30;
Sorte HS, Gjevik E, Sponheim E, Eiklid KL, Rødningen OK
OBJECTIVES: Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopment disorders with a complex genetic aetiology. The aim of this study was to identify copy number variations (CNVs) with a clinical significance for ASD. MATERIALS AND METHODS: Array-based comparative genomic hybridization was applied to detect CNVs in a clinically well-characterized population of 50 children and adolescents with ASD. RESULTS: Nine CNVs with predicted clinical significance were identified among eight individuals (detection rate 16%). Three of the CNVs are recurrently associated with ASDs (15q11.2q13.1) or have been identified in ASD populations (3p14.2 and t(8;12)(p23.1;p13.31)). The remaining regions (15q11.2, 10q21.1, Xp22.2, 16p13.3 and 22q13.1) have not been reported previously as candidate genes for ASD. CONCLUSION: This study identified five novel CNVs among the individuals. The causal relationship between identified CNVs and the ASD phenotype is not fully established. However, the genes involved are associated with ASD and/or other neuropsychiatric disorders, or implicated in synaptic and neuronal activity, thus suggesting clinical significance. Further identification of ASD-associated CNVs is required, together with a broad clinical characterization of affected individuals to identify genotype-phenotype correlations.
HubMed – addiction
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