Background

Lead exposure remains highly prevalent worldwide despite decades of research highlighting its link to numerous adverse health outcomes. In addition to well-documented effects on cognition, there is growing evidence of an association with antisocial behavior, including aggression, conduct problems, and crime. An updated systematic review on this topic, incorporating study evaluation and a developmental perspective on the outcome, can advance the state of the science on lead and inform global policy interventions to reduce exposure.

Objectives

We aim to evaluate the link between lead exposure and antisocial behavior. This association will be investigated via a systematic review of human epidemiological and experimental nonhuman mammalian studies.

Methods

The systematic review protocol presented in this publication is informed by recommendations for the conduct of systematic reviews in toxicology and environmental health research (COSTER) and follows the study evaluation approach put forth by the U.S. EPA Integrated Risk Information System (IRIS) program.

Data sources

We will search the following electronic databases for relevant literature: PubMed, BIOSIS and Web of Science. Search results will be stored in EPA’s Health and Environmental Research Online (HERO) database.

Study eligibility and criteria

Eligible human epidemiological studies will include those evaluating any population exposed to lead at any lifestage via ingestion or inhalation exposure and considering an outcome of antisocial behavior based on any of the following criteria: psychiatric diagnoses (e.g., oppositional defiant disorder (ODD), conduct disorder (CD), disruptive behavior disorders (DBD)); violation of social norms (e.g., delinquency, criminality); and aggression. Eligible experimental animal studies will include those evaluating nonhuman mammalian studies exposed to lead via ingestion, inhalation, or injection exposure during any lifestage. The following outcomes will be considered relevant: aggression; antisocial behavior; and altered fear, anxiety, and stress response.

Study appraisal and synthesis methods

Screening will be conducted with assistance from an artificial intelligence application. Two independent reviewers for each data stream (human, animal) will screen studies with highest predicted relevance against pre-specified inclusion criteria at the title/abstract and full-text level. Study evaluation will be conducted using methods adapted from the U.S. EPA IRIS program. After data extraction, we will conduct a narrative review and quantitative meta-analysis on the human epidemiological studies as well as a narrative review of the experimental animal studies. We will evaluate the strength of each evidence stream separately and then will develop a summary evidence integration statement based on inference across evidence streams.

中文翻译：

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铅暴露和反社会行为：系统审查方案

背景

尽管数十年的研究强调铅暴露与许多不良健康结果的联系，但铅暴露在世界范围内仍然非常普遍。除了对认知的影响有据可查之外，越来越多的证据表明它与反社会行为有关，包括攻击性、行为问题和犯罪。关于这一主题的最新系统综述，结合研究评估和对结果的发展视角，可以推进铅的科学状况，并为全球政策干预提供信息，以减少接触。

目标

我们的目的是评估铅暴露与反社会行为之间的联系。将通过对人类流行病学和实验性非人类哺乳动物研究的系统回顾来调查这种关联。

方法

本出版物中提出的系统审查方案以毒理学和环境健康研究 (COSTER) 系统审查的建议为依据，并遵循美国 EPA 综合风险信息系统 (IRIS) 计划提出的研究评估方法。

数据源

我们将在以下电子数据库中检索相关文献：PubMed、BIOSIS 和 Web of Science。搜索结果将存储在 EPA 的健康与环境在线研究 (HERO) 数据库中。

学习资格和标准

符合条件的人类流行病学研究将包括评估在任何生命阶段通过摄入或吸入接触铅的任何人群，并根据以下任何标准考虑反社会行为的结果：精神诊断（例如，对立违抗性障碍（ODD）、品行障碍） （CD）、破坏性行为障碍（DBD））；违反社会规范（例如违法、犯罪）；和攻击性。合格的实验动物研究将包括评估在任何生命阶段通过摄入、吸入或注射接触铅的非人类哺乳动物研究。以下结果将被视为相关：攻击性；反社会行为; 并改变恐惧、焦虑和压力反应。

研究评价和综合方法

筛查将在人工智能应用程序的协助下进行。每个数据流（人类、动物）的两名独立审稿人将根据标题/摘要和全文级别的预先指定的纳入标准筛选具有最高预测相关性的研究。研究评估将使用美国 EPA IRIS 计划改编的方法进行。数据提取后，我们将对人类流行病学研究进行叙述性回顾和定量荟萃分析，并对实验动物研究进行叙述性回顾。我们将分别评估每个证据流的强度，然后根据跨证据流的推断制定一份总结性证据整合声明。