Risk of Psychosis with Prescription Stimulant Use

项目总结/摘要 据估计，有350万美国儿童和青少年被开处方兴奋剂， 注意力缺陷多动障碍（ADHD）的治疗。大量的动物研究表明， 兴奋剂会诱导大脑多巴胺系统的长期变化，与在大脑中观察到的变化平行 精神病患者。尽管众所周知兴奋剂会导致精神病的急性发作， 缺乏关于兴奋剂是否会增加患精神病的长期风险的研究， 兴奋剂是否与精神病的早期发作有关。为了解决这些问题，校长 一位研究者（PI）提出了一项职业发展计划，该计划将哈佛教师的严格培训与 一个创新的研究议程，使用两种互补的方法来研究精神病的风险， 处方兴奋剂用途：1）一项使用电子病历的大规模纵向研究， 英格兰医疗保健系统比较儿童/青少年患精神障碍的风险， ADHD基于暴露于处方兴奋剂，和2）以患者为导向的临床研究， 患有首次发作精神病的人，以确定在疾病发作前使用处方兴奋剂是否 与早期精神病发作有关私家侦探是一名精神病学家， 具有精神分裂症神经影像学研究背景的疾病。这项赠款的培训目标是 主要研究者：1）发展流行病学专业知识，使用电子病历进行大规模 精神病的假定危险因素的研究; 1）发展儿童和青少年研究的专门知识 精神病学和首发精神病; 2）发展复杂统计学方面的高级技能，如倾向 评分匹配、生存分析和预测建模。这些目标将通过正式的 由国际公认的优秀科学家团队提供的课程和指导 与当前提案直接相关的研究领导者。拟议的研究项目符合 国家精神卫生研究所（NIMH）战略目标2关于绘制精神疾病轨迹， 早期干预。通过绘制从儿童/青少年到精神病发作的轨迹，这项研究 可能潜在地确定一个可改变的风险因素，该风险因素可能改变进展为精神病的可能性。的 成功完成本职业发展计划将有助于PI过渡到 独立调查员的长期目标是确定精神病的危险因素， 风险最大的人，并允许早期干预。此外，该奖项将为PI提供培训， 以及未来研究所需的工具，包括分析大规模多元素电子医疗 记录数据集与NIH大数据到知识（BD 2K）计划的目标保持一致。

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.