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童年逆境与5-羟色胺转运体基因启动子区域多态性作为物质使用障碍的风险因素:西班牙穆尔西亚的回顾性病例对照研究

Childhood adversities and 5-HTTLPR polymorphism as risk factors of substance use disorders: retrospective case-control study in Murcia (Spain).

作者信息

Navarro-Mateu Fernando, Quesada Mari Paz, Escámez Teresa, Alcaráz Mª José, Seiquer de la Peña Catherine, Salmerón Diego, Huerta José María, Vilagut Gemma, Chirlaque Maria Dolores, Navarro Carmen, Husky Mathilde, Kessler Ronald C, Alonso Jordi, Martínez Salvador

机构信息

Unidad de Docencia, Investigación y Formación en Salud Mental, Servicio Murciano de Salud, Murcia, Spain.

Departamento de Psicología Básica y Metodología, Universidad de Murcia, Murcia, Spain.

出版信息

BMJ Open. 2019 Sep 4;9(9):e030328. doi: 10.1136/bmjopen-2019-030328.

Abstract

OBJECTIVE

To explore the separate and joint associations of childhood adversities and 5-HTTLPR polymorphism as risk factors for substance use disorders among adults. : : Retrospective case-control study.

SETTING

Cases from the substance unit and controls from a representative sample of the adult general population in the metropolitan area of Murcia (Spain).

PARTICIPANTS

Cases were defined as outpatients 18 years old or older currently in the treatment for alcohol, opioids or cocaine use disorders in the clinical unit. Controls were randomly selected among individuals without substance use disorders who participated in the Psychiatric Enquiry to General Population in Southeast Spain-Murcia (PEGASUS-Murcia) project, a cross-sectional study of a representative sample of the adult general population. In all, 142 cases and 531 controls were interviewed and a subsample of 114 cases (80.3%) and 329 controls (62%) provided a biological sample.

EXPOSURE

A history of 12 childhood adversities, lifetime mental disorders and sociodemographic variables was assessed with the Composite International Diagnostic Interview (CIDI)version 3.0). Buccal swabs were obtained to genotype the 5-HTTLPR polymorphism with the biallelic and the triallelic classification.

MAIN OUTCOME AND MEASURE

Multivariable logistic regression models were performed to estimate adjusted ORs and 95% CI.

RESULTS

Childhood adversities were associated with an elevated risk of substance use disorders (OR=5.77, 95% CI 3.46 to 9.61). Homozygotes for the short allele of the 5-HTTLPR polymorphism also showed the elevated risk of substance use disorders for the biallelic and triallelic classification: (1.97 (1.10 to 3.55) and 2.01 (1.11 to 3.64), respectively). No evidence for gene × environment interactions was found.

CONCLUSIONS

Childhood adversities and the 5-HTTLPR polymorphism are involved in the aetiology of substance use disorders though findings exploring the existence of a gene-environment interaction were inconclusive.

摘要

目的

探讨童年逆境和5-羟色胺转运体基因启动子区(5-HTTLPR)多态性作为成年人物质使用障碍风险因素的单独及联合关联。::回顾性病例对照研究。

设置

病例来自物质使用障碍治疗单元,对照来自西班牙穆尔西亚市大都市区成年普通人群的代表性样本。

参与者

病例定义为临床单元中目前正在接受酒精、阿片类药物或可卡因使用障碍治疗的18岁及以上门诊患者。对照是从参与西班牙东南部穆尔西亚市普通人群精神病学调查(PEGASUS - 穆尔西亚)项目的无物质使用障碍个体中随机选取的,该项目是对成年普通人群代表性样本的横断面研究。总共对142例病例和531名对照进行了访谈,114例病例(80.3%)和329名对照(62%)的子样本提供了生物样本。

暴露因素

使用复合国际诊断访谈(CIDI)3.0版评估12种童年逆境史、终生精神障碍和社会人口统计学变量。采集颊拭子以对5-HTTLPR多态性进行双等位基因和三等位基因分类的基因分型。

主要结局和测量指标

采用多变量逻辑回归模型估计调整后的比值比(OR)和95%置信区间(CI)。

结果

童年逆境与物质使用障碍风险升高相关(OR = 5.77,95%CI 3.46至9.61)。5-HTTLPR多态性短等位基因纯合子在双等位基因和三等位基因分类中也显示出物质使用障碍风险升高:分别为1.97(1.10至3.55)和2.01(1.11至3.64)。未发现基因×环境交互作用的证据。

结论

童年逆境和5-HTTLPR多态性参与了物质使用障碍的病因学,但关于基因 - 环境交互作用存在的探索结果尚无定论。

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