Perinatal risk factors and genetic susceptibility for childhood psychopathology

描述（由申请人提供）：精神病学最近的一个显著进展是认识到精神健康问题可能起源于子宫。发展精神病理学的研究表明，早产（PTB）与破坏性行为和焦虑症的风险增加2- 3倍有关。然而，之前没有研究调查为什么肺结核与广泛的儿童疾病有关。此外，很少有研究将围产期流行病学和精神遗传学研究相结合的模型来理解发育性精神病理学的发展轨迹。本指导研究科学家发展奖（K01）的目的是支持候选人发展成为独立的科学家，其工作将致力于检查与可改变的产前精神疾病预测因素有关的围产期问题，同时考虑到遗传影响。为了实现这一目标，在修订后的申请中，候选人加强了她的多学科导师小组，反映了一个更集中的研究项目。他们将教她研究胎儿/儿童发育和精神遗传学的具体方法，并监督她的课程作业。为了使候选人能够成功地整合明显不同的学科，已经制定了导师团队监视和审查候选人进展的计划。正如前一组综述所建议的那样，研究计划被显著地改进和简化，以检验两个相互竞争的假设：(1)PTB的不同病因独立地影响破坏性和焦虑障碍的风险；(2) PTB，无论其病因如何，都与遗传易感性相互作用，直接增加了每种疾病的风险。研究计划提出了一个由两项相关研究组成的研究项目：1)纵向流行病学研究（研究1），研究对象为新英格兰国家围产期合作研究的2,022名儿童，随访至成年；2)纵向研究225名注意缺陷多动障碍（adhd）高、低风险儿童（研究2）。此外，还包括从母亲那里收集的孕期早期发育环境的回顾性数据，候选人将收集自己的数据，以最大限度地利用研究2中的基础设施来检验她的假设。这项研究具有重要的公共卫生意义。首先，它将有助于阐明儿童疾病发展的发育、生物学和遗传途径。随后确定非常早期可改变的儿童疾病风险因素将为早期和更有效的干预创造新的可能性。这可能有助于减轻患有发展性精神病理学的幼儿家庭的负担，同时也为儿童本身的治疗提供了新的可能性。总之，研究和培训计划是候选人过渡到独立研究者的核心，并将极大地有助于我们了解破坏性和焦虑障碍的可改变风险因素，以便未来干预。

DESCRIPTION (provided by applicant): One remarkable recent advance in psychiatry is the recognition that mental health problems can originate in utero. Research in developmental psychopathology has shown that preterm birth (PTB) is associated with a 2- to 3-fold increased risk of both disruptive behavior and anxiety disorders. However, no prior studies have examined why PTB is associated with a wide range of childhood disorders. Furthermore, few studies have integrated models based on research in perinatal epidemiology and psychiatric genetics to understand the trajectory of developmental psychopathology. The purpose of this Mentored Research Scientist Development Award (K01) is to support the development of the candidate to an independent scientist, whose work will be devoted to the examination of perinatal problems that are related to modifiable prenatal predictors of mental illness, taking into account genetic influences. To achieve this goal, in this revised application, the candidate has strengthened her multidisciplinary group of mentors reflecting a more focused program of research. They will teach her specific methods for studying fetal/child development and psychiatric genetics, and monitor her coursework. For the candidate to have a successful integration of apparently disparate disciplines, plans for the team of mentors to monitor and review the candidate's progress have been put in place. As suggested in the previous set of reviews, the research plan was significantly refined and simplified to test two competing hypotheses: (1) that different causes of PTB independently influence the risk of disruptive and anxiety disorders; and (2) that PTB, regardless of its cause, interacts with genetic susceptibility to directly increase the risk for each disorder. The research plan proposes a program of research comprised two related studies: 1) a longitudinal epidemiologic study of 2,022 children (Study 1) who were enrolled in the National Collaborative Perinatal Study - NewEngland and followed into adulthood and 2) a longitudinal study of 225 children at high and low risk for Attention Deficit Hyperactivity Disorder (Study2). Additionally, retrospective data collection of early developmental environment during pregnancy from mothers is included, where the candidate will collect her own data to test her hypotheses maximizing the infrastructure available in Study 2. This research has significant public health implications. First, it will help elucidate the developmental, biological, and genetic pathways through which childhood disorders develop. Subsequent identification of very early modifiable risk factors for childhood disorders will create new possibilities for earlier and more effective interventions. That may help relieve the burden in families with young children who have developmental psychopathology as well as providing new possibilities for treatment of the children themselves. Together, the research and training program are central to the candidate's transition to independence as an investigator and will contribute greatly to our understanding of modifiable risk factors for disruptive and anxiety disorders for future interventions.