The need for studies of acetaminophen's impact on risk-taking in daily life; reply to Ross and Holstege (2021).
The need for studies of acetaminophen's impact on risk-taking in daily life; reply to Ross and Holstege (2021).
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DOI：
10.1093/scan/nsab026
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发表时间：
2021-05-04
影响因子：
4.2
通讯作者：
Keaveney A
中科院分区：
文献类型：
--
作者：
Way BM;Peters E;Keaveney A
我们感谢Ross博士和Holstege博士提出的讨论在受控实验室环境之外对乙酰氨基酚的潜在行为影响的机会。在给编辑的信中，他们“建议在得出使用对乙酰氨基酚对日常生活有严重危害的结论之前，需要进行更多的研究”。我们由衷地同意。然而，我们尊重地不同意在手稿的“潜在影响”部分假设的合理性，即急性服用对乙酰氨基酚可能对行为和决策产生影响，超出传统上接受的疼痛和发烧的减少。事实上，提出这样的假设是激励未来研究的关键组成部分，以更好地了解服用这种药物的风险和益处。在美国，每天有数百万人服用对乙酰氨基酚，但这种药物对行为的影响在很大程度上尚未得到研究。我们根本不知道急性对乙酰氨基酚是否、何时、对谁会对日常生活中的思想、情绪或行为产生影响。Ross和Holstege没有引用任何数据来证明这一点。如果没有这些数据，就不可能知道对乙酰氨基酚在日常生活中可能产生的影响和影响大小。我们应该注意到，欧洲（Liew等人，2014）、北美（Rifas-Shiman等人，2020）和亚洲（Chen等人，2019）有越来越多的大型前瞻性研究文献将怀孕期间对乙酰氨基酚的使用与后代后期风险相关表型的表达（如多动症和外化行为）联系起来。在最近的一项研究中，胎便（新生儿的第一次粪便）中的对乙酰氨基酚水平预示着10岁时的多动症水平。子宫内暴露与多动症之间的关系是由背外侧前额叶连通性的改变介导的（Baker et al., 2020），这一区域与我们研究中使用的冒险任务的表现有关（Schonberg et al., 2012）。当然，如果在这些相关研究中确定对乙酰氨基酚是这些发育影响的诱因，这一发现并不一定意味着急性对乙酰氨基酚通过相同的途径产生任何行为影响。但是，表型重叠指出对乙酰氨基酚的潜在作用并不像以前认为的那样是惰性的。由于我们的研究是基于实验室的基础研究，因此根据这些数据提出临床建议确实为时过早。正如我们在手稿中假设的那样，对乙酰氨基酚可能会产生相反的行为效果，减少冒险行为，只需要对实验条件进行细微的改变。同样，服用对乙酰氨基酚的疾病（如头痛、感冒症状）也可能从根本上改变药物的心理作用。因此，正如我们所证明的那样（Roberts et al., 2019），对乙酰氨基酚的心理和行为影响可能依赖于状态和上下文，而不是报纸标题的简单分类。
We appreciate the opportunity raised by Drs Ross and Holstege to discuss the potential behavioral effects of acetaminophen beyond a controlled laboratory environment. In their letter to the editor, they “recommend that more research is needed prior to concluding that acetaminophen use is an acute danger to tasks of daily living”. We heartily agree. We respectfully disagree, however, about the reasonableness of hypothesizing in the ‘Potential Implications’ section of a manuscript that acute acetaminophen consumption could have effects on behavior and decision-making that go beyond conventionally accepted reductions in pain and fever. Indeed, proposing such hypotheses is a critical component of motivating future studies to better understand the risks and benefits of consuming this drug. Millions of individuals in the USA take acetaminophen each day, and the behavioral effects of this drug are largely unstudied. We simply do not know if, when or for whom acute acetaminophen might have influences on thought, emotions or behavior in daily life. Ross and Holstege cite no data to indicate otherwise. Without such data, it is impossible to know what effects and effect size, if any, acetaminophen might have in daily life. We should note that a growing body of literature from large, prospective studies exists in Europe (Liew et al., 2014), North America (Rifas-Shiman et al., 2020) and Asia (Chen et al., 2019) linking acetaminophen use during pregnancy with later expression of risk-taking-related phenotypes in the offspring such as ADHD and externalizing behavior. In a recent study, acetaminophen levels in meconium (the first feces of newborn infants) predicted hyperactivity levels at age 10. The relationship between in utero exposure and hyperactivity was mediated by alterations in dorsolateral prefrontal connectivity (Baker et al., 2020)—a region implicated in performance on the risk-taking task used in our study (Schonberg et al., 2012). Naturally, if acetaminophen is identified in these correlational studies as the causal agent for these developmental effects, this finding would not necessarily mean that acute acetaminophen exerts any behavioral effects via the same pathways. But, the phenotypic overlap points to the potential for acetaminophen not being as inert as previously thought.Because our study was laboratory-based basic research, it is indeed premature to make clinical recommendations based on these data. As hypothesized in our manuscript, acetaminophen could have the opposite behavioral effect, decreasing risktaking, with only a subtle alteration of the experimental conditions. Similarly, the medical condition for which acetaminophen was consumed (eg headache; cold symptoms) also could fundamentally change the drug’s psychological effects. Thus, as we have demonstrated (Roberts et al., 2019), acetaminophen’s psychological and behavioral effects are likely state-and contextdependent, defying the simple categorization of a newspaper headline.
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影响因子：
4.6
作者：
Roberts, Ian D.;Krajbich, Ian;Way, Baldwin M.
通讯作者：
Way, Baldwin M.
影响因子：
2.8
作者：
Rifas-Shiman, Sheryl L.;Cardenas, Andres;Oken, Emily
通讯作者：
Oken, Emily
影响因子：
4.3
作者：
Schonberg T;Fox CR;Mumford JA;Congdon E;Trepel C;Poldrack RA
通讯作者：
Poldrack RA
影响因子：
26.1
作者：
Liew, Zeyan;Ritz, Beate;Olsen, Jorn
通讯作者：
Olsen, Jorn
影响因子：
26.1
作者：
Baker, Brennan H.;Lugo-Candelas, Claudia;Baccarelli, Andrea A.
通讯作者：
Baccarelli, Andrea A.