Risk of Psychosis with Prescription Stimulant Use

项目摘要/摘要 据估计，有350万美国儿童和青少年服用处方兴奋剂 注意缺陷多动障碍(ADHD)的治疗。大量的动物研究表明 兴奋剂诱导大脑中多巴胺系统的长期变化，这种变化与在 精神病患者。尽管已知兴奋剂会导致精神错乱的急性发作， 缺乏关于兴奋剂是否会增加患精神病或精神障碍的长期风险的研究 兴奋剂是否与较早的精神病发病有关。为了解决这些差距，校长 调查员(PI)提出了一项职业发展计划，将哈佛大学教职员工的严格培训与 一项创新的研究议程，使用两种互补的方法来研究精神病的风险 处方兴奋剂使用：1)一项使用电子病历的大规模纵向研究 英格兰医疗系统比较儿童/青少年患精神障碍的风险 2)一项以患者为中心的临床研究 以确定首发精神病患者在发病前是否使用处方兴奋剂 与较早的精神病发作有关。PI是一位在精神病学方面具有临床专业知识的精神病学家 有精神分裂症神经影像研究背景的精神障碍。这笔赠款的培训目标是 对于PI：1)发展流行病学方面的专业知识，并使用电子病历进行大规模 精神病可能危险因素的研究；1)培养儿童和青少年研究方面的专门知识 精神病学和首发精神病；以及2)发展复杂统计方面的高级技能，如倾向 分数匹配、生存分析和预测建模。这些目标将通过正式的 由国际公认的非常合格的科学家团队进行的课程工作和指导 与当前提案直接相关的研究领域的领导者。建议的研究项目与 国家精神卫生研究所(NIMH)关于绘制精神疾病轨迹的战略目标2，以允许 早期干预。通过绘制从童年/青春期到精神病发作的轨迹，这项研究 可能确定一种可改变的危险因素，该危险因素可能改变进展为精神病的可能性。这个 成功完成这一职业发展计划将有助于PI过渡到 独立调查员，长期目标是确定精神病的风险因素，以针对 风险最大的个人，并允许及早干预。此外，该奖项还将为PI提供培训 以及未来涉及大规模多元素电子医疗分析的研究所需的工具 根据NIH大数据到知识(BD2K)计划的目标记录数据集。

Project Summary / Abstract An estimated 3.5 million American children and adolescents are prescribed prescription stimulants for the treatment of attention deficit hyperactivity disorder (ADHD). A large body of animal research demonstrates that stimulants induce long-term changes in dopamine systems in the brain that parallel changes observed in individuals with psychosis. Although it is known that stimulants can precipitate acute episodes of psychosis, there is a lack of research on whether stimulants increase long-term risk of developing a psychotic disorder or whether stimulants are associated with an earlier onset of psychosis. To address these gaps, the principal investigator (PI) proposes a career development program that blends rigorous training by Harvard faculty with an innovative research agenda that uses two complementary approaches to study the risk of psychosis with prescription stimulant use: 1) A large-scale longitudinal study using electronic medical records for a New England healthcare system to compare the risk of developing a psychotic disorder in children/adolescents with ADHD based on exposure to prescription stimulants, and 2) a patient-oriented clinical research study in individuals with first-episode psychosis to determine if prescription stimulant use prior to illness onset is associated with an earlier onset of psychosis. The PI is a psychiatrist with clinical expertise in psychotic disorders with a background in neuroimaging research in schizophrenia. Training objectives for this grant are for the PI to: 1) Develop expertise in epidemiology and use of electronic medical records to perform large-scale studies of putative risk factors for psychosis; 1) Develop expertise in research in child and adolescent psychiatry and first-episode psychosis; and 2) Develop advanced skills in complex statistics such as propensity score matching, survival analysis and predictive modeling. These goals will be accomplished by formal coursework and mentorship by an exceptionally-qualified team of scientists who are internationally-recognized leaders in research directly relevant to the current proposal. The proposed research project aligns with the National Institute of Mental Health (NIMH) Strategic Objective 2 on charting mental illness trajectories to allow early intervention. By charting the trajectory from childhood/adolescence to onset of psychosis, this research may potentially identify a modifiable risk factor that could alter the likelihood of progression to psychosis. The successful completion of this career development plan will assist the PI in making the transition to an independent investigator with the long-term goal of identifying risk factors for psychosis to target those individuals most at risk and allow early intervention. In addition, this award will provide the PI with the training and tools necessary for future studies involving the analysis of large-scale multi-element electronic medical record data sets in alignment with objectives of the NIH Big Data to Knowledge (BD2K) program.