Polygenic Prediction of Suicide: Clinical, Ethical and Psychosocial Impact

自杀的多基因预测：临床、伦理和社会心理影响

• 批准号: 10649055
• 负责人: Paul Stuart Appelbaum
• 金额: $ 42.65万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649055
• 关键词: Adult; Affect; American; Area; Attitude; Awareness; Behavior; Belief; Benefits and Risks; Cause of Death; Cessation of life; Clinical; Clinical Medicine; Data; Decision Making; Development; Disease; Dizygotic Twins; Electronic Health Record; Empathy; Ethics; Family member; Feeling hopeless; Feeling suicidal; Focus Groups; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genome; Health; Heritability; Hospitalization; Individual; Injury; Interpersonal Relations; Intervention; Interview; Investigation; Knowledge; Lead; Life; Literature; Medical; Mental disorders; Meta-Analysis; Methods; Minor; Outcome; Participant; Patients; Perception; Persons; Pharmaceutical Preparations; Physicians; Population Research; Primary Care Physician; Prognosis; Provider; Psychiatrist; Psychiatry; Psychosocial Factor; Public Health; Reaction; Recommendation; Research; Research Personnel; Resort; Respondent; Risk; Risk Factors; Risk Reduction; Self Perception; Self-Injurious Behavior; Single Nucleotide Polymorphism; Stigmatization; Suicide; Suicide attempt; Suicide prevention; Surveys; Symptoms; Syndrome; Testing; Time; Twin Studies; Uncertainty; United States; Variant; approach behavior; clinical care; clinical practice; depressive symptoms; effective intervention; emotional reaction; expectation; experience; experimental study; follow-up; genetic information; genetic predictors; genetic variant; genome wide association study; improved; knowledge base; polygenic risk score; precision medicine; premature; preventive intervention; primary care patient; prognostic; psychosocial; reducing suicide; reproductive; risk perception; risk variant; social; suicidal; suicidal behavior; suicidal morbidity; suicidal patient; suicidal risk; suicide rate; tool; treatment response; willingness

Suicide is a leading cause of death in the U.S. and a major public health problem, with hundreds of thousands of suicide attempts and tens of thousands of deaths annually. Unlike several other leading causes of death, progress in reducing suicide rates has been limited, in part because of an extremely limited ability to predict which individuals will attempt or die by suicide. Indeed, a recent meta-analysis of studies that attempted to predict suicidality based on putative risk factors found that predictive accuracy was barely better than chance and had shown no significant improvement over five decades. In this context, recent years have seen increasing enthusiasm regarding the prospect of using genetic information to predict suicide risk. In particular, researchers have recently developed polygenic risk scores (PRS), which use data from genome-wide association studies (GWAS) to estimate a person's relative genetic susceptibility to a particular health outcome (in this case, suicide) by aggregating all risk variants present in the person's genome, weighted by the strength of each variant's association with the outcome in question. Early research suggests that PRS for suicide have significant predictive power, and the prospect of using PRS to predict individuals' risk of suicide has generated significant excitement as a possible precision medicine tool for identifying people in need of intervention and ultimately preventing suicide deaths. However, there are also significant reasons for concern. For instance, if high PRS for suicide are misinterpreted in a fatalistic manner, this could lead to hopelessness among patients or premature reliance on intrusive or coercive approaches to risk-reduction among family members and clinicians. Low PRS could potentially lead to false reassurance. PRS could also affect treatment-related beliefs, patient-provider relationships, and stigmatization of at-risk individuals. The proposed research will investigate attitudes and beliefs about the prospect and implications of using PRS to predict suicide risk in clinical care, using surveys and qualitative interviews of primary care patients with symptoms of depression (Aim 1) and of primary care physicians and psychiatrists (Aim 2). Among the parameters examined for patients will be willingness to receive genetic predictions of suicide risk and emotional reactions to the receipt of such predictions; anticipated impact of suicide PRS on self-perceptions, reproductive decision-making, life planning, familial and interpersonal relationships, treatment-seeking, patient-provider relationships, and actual suicide risk; and other perceived risks and benefits. Physicians will be asked about perceived clinical utility and likely impact on clinical decisions, along with other perceived benefits and risks. We will also conduct an experimental study of physicians, examining the effects of PRS-based suicide risk information (i.e., mock electronic health record summaries) on putative decisions about clinical care (Aim 3). By investigating how the prospect of PRS-based suicide prediction is received by patients and physicians, the proposed research will help to anticipate the ethical, clinical, and societal implications of polygenic prediction of suicide.

自杀是美国人死亡的主要原因，也是一个主要的公共卫生问题， 自杀未遂和每年数万人死亡。与其他几个主要死亡原因不同， 在降低自杀率方面的进展是有限的，部分原因是预测自杀率的能力极其有限。 哪些人会试图自杀或死于自杀。事实上，最近的一项荟萃分析研究，试图 基于假定的风险因素预测自杀倾向发现，预测的准确性几乎不比偶然性高 并且在过去的五十年里没有表现出显着的改善。在这种背景下，近年来， 人们对利用遗传信息预测自杀风险的前景越来越感兴趣。特别是， 研究人员最近开发了多基因风险评分（PRS），该评分使用全基因组数据， 关联研究（GWAS），以估计一个人对特定健康结果的相对遗传易感性 (in这种情况下，自杀）通过聚合存在于人的基因组中的所有风险变体， 每种变异与所讨论的结果之间的联系。早期的研究表明，自杀的PRS 显著的预测能力，以及使用PRS预测个人自杀风险的前景已经产生 作为一种可能的精确医学工具，用于识别需要干预的人， 最终防止自杀。然而，也有令人关切的重要原因。例如，如果 自杀的高PRS被以宿命论的方式误解，这可能会导致患者感到绝望 或过早依赖侵入性或强制性方法来减少家庭成员的风险， 临床医生低PRS可能导致虚假保证。PRS也可能影响治疗相关的 信仰，病人与提供者的关系，以及对高危个体的污名化。拟议的研究将 调查对使用PRS预测自杀风险的前景和影响的态度和信念， 临床护理，使用调查和定性访谈的初级保健患者的抑郁症状 (Aim 1）和初级保健医生和精神科医生（目标2）。在检查的患者参数中， 将愿意接受自杀风险的遗传预测和接受这种预测的情绪反应， 预测;自杀PRS对自我感知、生殖决策、生活规划的预期影响， 家庭和人际关系、寻求治疗、患者-提供者关系和实际自杀 风险;以及其他感知的风险和收益。医生将被问及感知的临床效用， 对临床决策的影响，沿着其他感知的获益和风险。我们亦会进行一项 医生的实验研究，检查基于PRS的自杀风险信息的影响（即，模拟 电子健康记录摘要）关于临床护理的假定决定（目标3）。通过调查 基于PRS的自杀预测的前景受到患者和医生的欢迎，拟议的研究将 有助于预测自杀多基因预测的伦理，临床和社会影响。