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首页> 外文期刊>Archives of general psychiatry. >Association of polymorphisms in genes regulating the corticotropin-releasing factor system with antidepressant treatment response.
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Association of polymorphisms in genes regulating the corticotropin-releasing factor system with antidepressant treatment response.

机译：协会多态性的基因调节促肾上腺皮质激素的释放因子体系抗抑郁药物治疗的反应。

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CONTEXT: The corticotropin-releasing factor (CRF, or corticotropin-releasing hormone) and arginine vasopressin systems have been implicated in the pathophysiology of anxiety and depressive disorders and response to antidepressant treatment. OBJECTIVE: To study the association of genetic variants in 10 genes that regulate the CRF and arginine vasopressin systems with treatment response to citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample (N = 1768). DESIGN: Pharmacogenetic association study derived from the STAR*D study, a multicenter, prospective, open, 12-week effectiveness trial. SETTING: Outpatient primary care and psychiatric clinics. Patients Individuals with nonpsychotic major depressive disorder for whom DNA was available who were subsequently treated with citalopram hydrobromide for 4 to 12 weeks. Intervention Flexible doses of citalopram. Main Outcome Measure Association of genetic polymorphisms in genes encoding the CRF system with response and remission to citalopram treatment at exit visit. RESULTS: One single-nucleotide polymorphism (SNP) (rs10473984) within the CRHBP locus showed a significant association with both remission (P = 6.0 x 10(-6); corrected, P = .0026) and reduction in depressive symptoms (P = 7.0 x 10(-7); corrected, P = .00031) in response to citalopram. The T allele of this SNP was associated with poorer treatment outcome in 2 of the 3 ethnic subsamples (African American and Hispanic), despite large differences in minor allele frequency. This association was more pronounced in patients with features of anxious depression (P = .008). The nonresponse allele was shown to be associated with overall higher plasma corticotropin levels and more pronounced dexamethasone suppression of corticotropin. CONCLUSIONS: These data indicate that a genetic variant within the CRHBP locus affects response to citalopram in African American and Hispanic patients, suggesting a role for this gene and for the CRF system in antidepressant treatment response.
机译：背景:促肾上腺皮质激素的释放因子(CRF,促肾上腺皮质激素释放激素或)和精氨酸抗利尿激素系统已经涉及病理生理学的焦虑和抑郁障碍和应对的抗抑郁药治疗。在10基因调控的遗传变异CRF和精氨酸加压素系统西酞普兰治疗反应测序治疗方案来缓解抑郁症(STAR * D)样本(N = 1768)。药理遗传学协会来源于学习STAR * D研究中,多中心,前瞻性,开放,12周的有效性试验。门诊初级保健和精神病诊所。患者个人nonpsychotic专业抑郁症的DNA后来和西酞普兰治疗吗氢溴酸盐为4至12周。灵活的剂量的西酞普兰。衡量遗传多态性协会基因编码的响应和CRF系统缓解西酞普兰治疗出口访问。结果:一个单核苷酸多态性(SNP)在CRHBP轨迹显示(rs10473984)重要的协会与缓解(P =6.0 x 10 (6);在抑郁症状(P = 7.0 x 10 (7);纠正,P = .00031)在回应西酞普兰。T等位基因的SNP是相关联的贫穷的治疗效果在2 3的民族次级样本(非洲裔美国人和西班牙裔),尽管小等位基因之间存在较大的差异频率。焦虑抑郁的患者的特征(P = .008)。与整体较高的等离子体有关促肾上腺皮质激素水平,更加明显地塞米松抑制促肾上腺皮质激素。结论:这些数据表明,一个基因变体在CRHBP轨迹影响反应在非洲裔美国人和西班牙裔西酞普兰病人对这种基因和暗示作用抗抑郁药物治疗CRF系统响应。

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