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步是认识到精神健康问题可以起源于子宫。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，之前没有研究研究为什么肺结核与广泛的儿童障碍有关。此外，很少有研究在围产期流行病学和精神病学遗传学研究的基础上整合模型来了解发育精神病理学的发展轨迹。该指导研究科学家发展奖(K01)的目的是支持候选人发展为一名独立科学家，其工作将致力于检查与可修改的精神疾病产前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，在这份修订后的申请中，候选人加强了她的多学科导师小组，以反映更有针对性的研究计划。他们将教授她研究胎儿/儿童发育和精神遗传学的具体方法，并监督她的课程。为了让候选人成功地整合明显不同的学科，导师团队已经制定了监督和审查候选人进展的计划。正如之前的一组综述所建议的那样，研究计划被显著地改进和简化，以测试两个相互竞争的假设：(1)不同的肺结核原因独立地影响破坏性和焦虑性障碍的风险；(2)无论其原因如何，肺结核与遗传易感性相互作用，直接增加每种疾病的风险。该研究计划提出了一项由两项相关研究组成的研究计划：1)对2,022名儿童进行的纵向流行病学研究(研究1)，这些儿童参加了国家合作围产期研究-新英格兰并一直跟踪到成年；2)对225名患有注意力缺陷多动障碍的高风险和低风险儿童进行的纵向研究(研究2)。此外，还包括从母亲那里收集怀孕早期发育环境的回溯性数据，候选人将收集自己的数据来检验她的假设，使研究2中可用的基础设施最大化。这项研究具有重大的公共卫生意义。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。随后确定儿童障碍的非常早期的可改变的危险因素将为更早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育性精神病儿童的家庭的负担，并为儿童本身的治疗提供新的可能性。总而言之，研究和培训计划是候选人向独立调查员过渡的核心，并将极大地有助于我们了解未来干预措施中破坏性和焦虑性障碍的可修改风险因素。

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.