Polygenic Risk Scores in Child and Adolescent Psychiatry: Ethical, Clinical, and Legal Implications

项目总结 最近，包括精神分裂症在内的500多个与各种精神疾病有关的基因组基因座， 抑郁症和自闭症谱系障碍已经被识别出来。这使得有可能生成 多基因风险评分(PR)根据不同精神疾病的风险对个体进行分层比较 对普通民众来说。作为一种预测工具，精神病学PR在以下情况下可能最有价值 适用于发病前的个人。在大约75%的病例中，精神障碍的发病 或先兆特征出现在成年期早期，这使得精神病学的PR可能对儿童和 青少年。减贫战略有可能改进早期识别，并导致加强监测和 可能预防或推迟发病，并将发病率和自杀风险降至最低的干预措施，第二 是美国10-24岁儿童的主要死因。尽管他们有希望，但PrS可能特别危险 在精神病学的背景下，我们的初步工作发现，PRS已经被用于 儿童和青少年精神病学。人们对精神疾病有很大的耻辱，并且有滥用 在美国，“不良”行为或精神疾病的“预言者”。因此，精神病学的PRS可能是另一种工具 用来对付精神疾病患者。此外，精神病学PR可以说是第一个与 有能力为任何个人产生精神障碍的风险预测，并且存在关键的法律漏洞 在保护这些信息的隐私和防止遗传歧视方面。为了促进 在儿童和青少年中负责任地使用精神科PR，我们将使用混合方法 包括定性、定量和法律分析，以：1)让利益相关者(即患者、 父母/照顾者、临床医生)，通过检查他们对精神科PR是否应该 使用以及如果使用，如何使用；以及2)检查法律和监管环境，以确定可能的保障措施 这是必要的。尽管其中一些差距也适用于其他遗传信息，但我们将专注于识别 针对精神病患者或有风险的个人可能使用和误用精神科PR的潜在政策解决方案 精神障碍，几乎占美国人口的30%。这项研究的长期目标是发展 道德上合理和经验丰富的指导方针，以应对因使用 儿童和青少年的精神科康复服务。以美国国立卫生研究院资助的儿童和青少年精神病学为基础 遗传学调查(CAPGS)，调查儿童和青少年精神病学家对PR的看法 (3R00HG008689-05S1)，当前提案的目标是使用混合方法设计来检查： 1)精神科PR临床应用面临的挑战，2)主要利益相关者对精神科PR的看法，以及 3)针对基于精神疾病的隐私侵犯和歧视的法律保护方面的差距。

PROJECT SUMMARY Recently, more than 500 genomic loci associated with various psychiatric disorders, including schizophrenia, depression, and autism spectrum disorders, have been identified. This makes it possible to generate polygenic risk scores (PRS) to stratify individuals by risk for different psychiatric disorders compared to the general population. As a prediction tool, psychiatric PRS would likely be most valuable when applied to individuals before the onset of illness. In about 75% of cases, the onset of psychiatric disorders or prodromal features occurs by early adulthood making psychiatric PRS likely most useful for children and adolescents. PRS have the potential to improve early identification, and lead to enhanced monitoring and interventions to potentially prevent or delay onset, and minimize morbidity and risk for suicide, the second leading cause of death in the U.S. in ages 10–24. Despite their promise, PRS could be especially perilous in the context of psychiatry, and our preliminary work has found that PRS are already being used in child and adolescent psychiatry. There is significant stigma around mental illness, and a history of misuse of “predictors” of “undesirable” behaviors or mental illness in the US. Thus, psychiatric PRS could be another tool used against patients with psychiatric disorders. Further, psychiatric PRS are arguably the first tool with the capacity to generate risk predictions about psychiatric disorders for any individual and there are key legal gaps in the protection of the privacy of this information and the prevention of genetic discrimination. To promote responsible use of psychiatric PRS in children and adolescents, we will use a mixed-methods approach that includes qualitative, quantitative, and legal analysis to: 1) give voice to stakeholders (i.e., patients, parents/caregivers, clinicians) by examining their perspectives regarding whether psychiatric PRS should be used and, if so, how; and 2) examine the legal and regulatory landscape to identify what safeguards may be necessary. Although some of these gaps also apply to other genetic information, we will focus on identifying potential policy solutions for the likely uses and misuses of psychiatric PRS against individuals with or at risk of psychiatric disorders, almost 30% of the US population. The long-term goal of this research is to develop ethically-justified and empirically-informed guidelines to address the ethical challenges raised by the use of psychiatric PRS with children and adolescents. Building on our NIH-funded Child and Adolescent Psychiatric Genetics Survey (CAPGS), which examined child and adolescent psychiatrists’ perspectives about PRS (3R00HG008689-05S1), the objective of the current proposal is to use a mixed-methods design to examine: 1) challenges in the clinical use of psychiatric PRS, 2) key stakeholders’ perspectives on psychiatric PRS, and 3) gaps in legal protections against privacy violations and discrimination based on psychiatric PRS.