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内。发育精神病理学的研究表明，早产与破坏性行为和焦虑症的风险都增加了2到3倍。然而，之前没有研究研究为什么早产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的发展，使其成为一名独立科学家，其工作重点将是考虑到遗传影响，研究可修改的产前预测因素对精神疾病的影响。为了实现这一目标，候选人的多学科导师小组将教授她研究胎儿/儿童发育和精神遗传学的具体方法，并指导她选择课程。对于候选人成功地整合这些不同的科学学科，导师团队将积极监督和审查候选人的进展。 研究计划得到了极大的改进和简化，并提出了一个由两项相关研究组成的研究计划：1)对参加新英格兰国家合作围产期研究并一直跟踪到成年的2,022名儿童进行了纵向流行病学研究；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了纵向研究。将检验两个相互矛盾的假设：(1)不同的早产原因独立影响破坏性行为和焦虑症的风险；(2)早产，无论其原因如何，都与遗传易感性相互作用，直接增加每种疾病的风险。在这项修订后的申请中，建议在杰克逊实验室进行遗传和表观遗传学培训，以取代增设的纵向统计讲习班。作为培训的一部分，候选人将进行回溯性数据收集，以收集关于怀孕期间早期发育环境的补充信息，同时最大化第二项研究中可用的基础设施。这项研究在帮助阐明儿童疾病发展的发育、生物学和遗传途径方面具有重大的公共卫生意义。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。这可能会通过为幼儿提供新的治疗方法来帮助减轻有年幼儿童表现出精神病理的家庭的负担。 总而言之，这项研究和培训计划将影响候选人向独立调查员的过渡，并将极大地有助于我们了解破坏性行为和焦虑症的可修改风险因素，以便规划和测试未来的干预措施。

DESCRIPTION (provided by applicant): A notable recent advance in psychiatry is the recognition that mental health problems can originate in-utero. Research in developmental psychopathology has shown that preterm birth is associated with a 2- to 3-fold increased risk of both disruptive behavior and anxiety disorders. However, no prior studies have examined why preterm birth 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 become an independent scientist whose work will focus on the impact of modifiable prenatal predictors on mental illness, taking into account genetic influences. To achieve this goal, the candidate's multidisciplinary group of mentors will teach her specific methods for studying fetal/child development and psychiatric genetics, and guide her selection of coursework. For the candidate successfully integrate these disparate scientific disciplines, the team of mentors will actively monitor and review the candidate's progress. The research plan was significantly refined and simplified, and proposes a program of research comprised of two related studies: 1) a longitudinal epidemiologic study of 2,022 children who were enrolled in the National Collaborative Perinatal Study - New England and followed into adulthood and 2) a longitudinal study of 225 children at high and low risk for Attention Deficit Hyperactivity Disorder. Two competing hypotheses will be tested: (1) that different causes of preterm birth independently influence the risk of disruptive behavior and anxiety disorders; and (2) that preterm birth, regardless of its cause, interacts with genetic susceptibility to directly increase the risk for each disorder. In this revised application, genetic and epigenetic training at Jackson Lab is proposed in a place of the additional longitudinal statistics workshop. As a part of the training, the candidate will conduct retrospective data collection to gather supplemental information on the early developmental environment during pregnancy while maximizing the infrastructure available in the second study. This research has significant public health implications in helping to 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. This may help relieve the burden in families with young children exhibiting psychopathology by informing new treatment approaches for young children. Together, this research and training program will effect the candidate's transition to independence as an investigator and will contribute greatly to our understanding of modifiable risk factors for disruptive behavior and anxiety disorders for planning and testing future interventions.