From the Department of Psychiatry, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil; the Department of Genetics, Universidade Federal do Rio Grande do Sul, Brazil; the Department of Basic Health Sciences. Universidade Federal de Ciências da Saúde de Porto Alegre; the Department of Psychiatry, Universidade de São Paulo, Brazil; the Center of Mathematics Computation and Cognition, Universidade Federal do ABC, Brazil; the Postgraduate Program in Epidemiology, Universidade Federal de Pelotas, Brazil; and the National Institute for Developmental Psychiatry for Children and Adolescents, Brazil.
Am J Psychiatry. 2015 Oct;172(10):978-85. doi: 10.1176/appi.ajp.2015.14070896. Epub 2015 Aug 28.
Replication of scientific findings is a major challenge in biomedical research. In psychiatry, the identification of measured gene-environment interactions (G×E) has promoted a heated debate over the past decade, with controversial results about its influence on disorders such as major depression. The authors sought to replicate a 2003 study on G×E in youth depression in a large birth cohort from a diverse setting.
Using data from the 1993 Pelotas Birth Cohort Study, and adopting a design as similar as possible to that of the original study, the authors tested whether the relationship between childhood maltreatment and a subsequent depressive episode diagnosis was moderated by 5-HTTLPR genotype. Of 5,249 individuals assessed at birth and followed up to age 18, data on the evaluation for depressive episodes in early adulthood, on childhood maltreatment, and on genotype were available for 3,558 participants, of whom 2,392 remained after conservative screening for previous depressive symptoms. Associations were investigated with logistic regression analyses and controlling for potential confounders.
The results replicated important findings of the original study, this time in a sample of young adults from a middle-income country: there was a differential dose-response relationship between childhood maltreatment and major depression according to 5-HTTLPR genotype.
After following a research strategy as comparable as possible to that of the original study, the results corroborated the existence of a measured G×E, now in a large sample from a different sociocultural context. These findings provide further evidence that a genetic variant in the 5-HTTLPR moderates the link between childhood maltreatment and youth depression.
科学发现的复制是生物医学研究中的一个主要挑战。在精神病学中，测量基因-环境相互作用（G×E）的识别在过去十年中引发了激烈的争论，其对诸如重度抑郁症等疾病的影响存在争议。作者试图在一个来自不同环境的大型出生队列中复制 2003 年关于青年抑郁症 G×E 的研究。
使用来自 1993 年佩洛塔斯出生队列研究的数据，并采用尽可能类似于原始研究的设计，作者测试了儿童期虐待与随后的抑郁发作诊断之间的关系是否受到 5-HTTLPR 基因型的调节。在出生时评估的 5249 人中，有 3558 名参与者在成年早期评估了抑郁发作，有 3558 名参与者有儿童期虐待的信息，有 3558 名参与者有基因型的信息，其中 2392 名参与者在经过保守的先前抑郁症状筛查后仍保留。采用逻辑回归分析并控制潜在混杂因素来研究关联。
研究结果复制了原始研究的重要发现，这一次是在一个来自中等收入国家的青年成年人样本中：根据 5-HTTLPR 基因型，儿童期虐待与重度抑郁症之间存在不同的剂量-反应关系。
在遵循尽可能类似于原始研究的研究策略后，结果证实了测量的 G×E 的存在，现在是在一个不同社会文化背景的大样本中。这些发现进一步证明了 5-HTTLPR 中的遗传变异调节了儿童期虐待与青年抑郁症之间的联系。
