Further evidence of an association between a genetic variant in BMP7 and treatment response to SSRIs in major depressive disorder
Further evidence of an association between a genetic variant in BMP7 and treatment response to SSRIs in major depressive disorder
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BMP7 基因变异与重度抑郁症 SSRI 治疗反应之间关联的进一步证据
DOI：
10.1038/jhg.2013.52
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发表时间：
2013
影响因子：
3.5
通讯作者：
Ikeda M and Iwata N
中科院分区：
文献类型：
--
作者：
Esaki K;Kondo K;Hatano M;Saito T;Kishi T;Umene-Nakano W;Yoshimura R;Nakamura J;Ozaki N;Ikeda M and Iwata N
严重抑郁障碍(MDD)是一种常见的精神障碍，终生患病率很高(10%-20%)，是导致残疾和死亡的主要原因。虽然抗抑郁药经常被开出，但个体对抗抑郁药的反应是高度不同的，因此，MDD患者治疗效果的预测指标有望确定精神科医生的最佳治疗策略。药物遗传学和药物基因组学(PGx)研究可以提供这样的预测因素(即遗传变异)，尽管这些研究都没有被证明在MDD或其他精神疾病的临床环境中有用。缺乏临床实用性的一个原因是每个基因变异对抗抑郁(或抗精神病)疗效的影响比根据药物遗传学/药物基因组学概念预期的要小。1此外，最近的证据表明，与治疗反应相关的遗传变异是高度多基因的，遗传率被假设为42%。2这些发现表明，将需要大量的受试者以及使用Meta分析的独立复制研究来从筛选数据集中获得有意义的结果。为了解决这个问题，在当前的研究中，我们使用日本人群对遗传相关性进行了验证研究，并对在缓解抑郁的排序治疗替代方案(STAR*D)研究中检测到的单核苷酸多态(SNPs)进行了荟萃分析，3该研究旨在确定选择性5-羟色胺再摄取抑制剂(SSRIs)对MDD的治疗效果。研究样本包括224名接受SSRIs治疗的MDD患者(男103，女121，平均年龄±SD？47.1±15.0岁)。关于临床表型的详细信息在其他地方描述。4然而，在本研究中，我们只纳入了汉密尔顿抑郁量表(HAM-D)17项中最低抑郁严重程度评分为14分的患者，根据STAR*D的纳入标准，年龄范围为18~75岁。3这些患者中，104例、63例和57例分别接受氟伏沙明、舍曲林和帕罗西汀治疗8周(单一治疗)。分别于基线(0周：平均±SD？21.0±4.9)和治疗后(8周：平均±SD？10.1±6.1)评定HAM-D评分。一位应答者是
Major depressive disorder (MDD) is a common mental disorder with a high lifetime prevalence (10–20%), and is a leading cause of disability and mortality. Although antidepressants are often prescribed, the individual response to antidepressants is highly variable, and predictors for treatment efficacy in MDD patients are therefore anticipated to identify the optimal treatment strategy for psychiatrists. Pharmacogenetic and pharmacogenomic (PGx) studies can provide such predictive factors (that is, genetic variants), although none of these have proven useful in the clinical setting for MDD or other psychiatric disorders. One reason for this lack of clinical utility is related to the smaller effect size of each genetic variant on antidepressant (or antipsychotic) efficacy than would be expected in accordance with the pharmacogenetic/pharmacogenomic concept. 1 Moreover, recent evidence suggests that the genetic variants associated with treatment response are highly polygenic, and heritability is assumed to be 42%. 2 These findings indicate that a large number of subjects, as well as independent replication studies with meta-analyses, will be required to derive meaningful results from screening data sets.To address this issue, in the current study, we performed a validation study on genetic associations using the Japanese population and a meta-analysis of single nucleotide polymorphisms (SNPs) detected in the Sequenced Treatment Alternatives to Relieve Depression (STAR* D) study, 3 which was performed to determine the treatment efficacy of selective serotonin reuptake inhibitors (SSRIs) in MDD. The sample comprised 224 MDD subjects treated with SSRIs (male¼ 103, female¼ 121, mean age±sd ¼ 47.1±15.0 years). Detailed information on the clinical phenotypes is described elsewhere. 4 In the current study, however, we included only patients with a minimum depression severity score of 14 out of 17 items on the Hamilton Depressive Rating scale (HAM-D) and an age range from 18 to 75 years according to the inclusion criteria of STAR* D. 3 Of these patients, 104, 63 and 57 were treated with fluvoxamine, sertraline and paroxetine, respectively, for 8 weeks (monotherapy). The HAM-D scores were assessed in each patient at baseline (0 weeks: mean±sd ¼ 21.0±4.9) and after treatment (8 weeks: mean±sd ¼ 10.1±6.1). A responder was
影响因子：
17.7
作者：
Uher, Rudolf
通讯作者：
Uher, Rudolf
影响因子：
9.8
作者：
Purcell, Shaun;Neale, Benjamin;Sham, Pak C.
通讯作者：
Sham, Pak C.