Prenatal Factors and Risk of Bipolar Disorder

描述(申请人提供)：在本次调查中，产前因素和双相情感障碍(PFB)项目，我们将审查早期发育侮辱和成人双相情感障碍风险之间的关系。双相情感障碍是一种高度致残的精神疾病。尽管进行了大量研究，但其病因尚不清楚，部分原因是缺乏严格的流行病学研究。在PFB研究中，我们的目标是更好地了解双相情感障碍的早期发展风险因素，并评估这些因素是否为精神分裂症所特有。为此，我们将利用儿童健康和发展研究的出生队列，这是加利福尼亚州奥克兰地区具有代表性的大量出生样本。这项研究具有许多优点，包括从产前开始收集的丰富的前瞻性数据，以及几乎所有怀孕时都冷冻存储的母体血清样本。我们之前在这个队列中对精神分裂症进行了跟踪调查，在宫内暴露与该疾病风险之间的关系上得出了几个有趣的发现。我们的目标是：1)检查宫内感染和免疫暴露之间的关系，可以使用存档的产前血清样本来检测，与双相情感障碍的风险之间的关系。这些暴露包括产前流感和弓形虫病感染，以及细胞因子升高；2)检查早期发育性非感染因素与双相情感障碍的关系。这些因素包括母亲体重指数升高、母亲吸烟和饮酒、胎儿发育迟缓和胎龄。3)评估可能调节早期发育暴露与双相情感障碍风险之间观察到的关联的途径。我们将使用结构化访谈在队列中诊断双相情感障碍的病例，并使用嵌套病例对照和队列分析来评估详细的早期发育暴露与双相情感障碍之间的关系。这些研究的目的应该使我们能够确定双相情感障碍的重要原因。这将有助于制定通过消除或减少已识别的危险因素来预防双相情感障碍的策略，有助于我们理解双相情感障碍的发病机制，并最终揭示与危险因素相互作用的易感基因。

DESCRIPTION (provided by applicant): In the present investigation, the Prenatal Factors and Bipolar Disorder (PFB) Project, we shall examine the relationship between early developmental insults and risk of adult bipolar affective disorder. Bipolar disorder is a highly disabling psychiatric illness. Despite considerable research, its etiologies are not well understood, in part due to a lack of rigorous epidemiologic studies. In the PFB study, we aim to better understand early developmental risk factors for bipolar disorder, and assess whether these factors are specific to schizophrenia. For this purpose, we shall utilize the birth cohort of the Child Health and Development Study, a large and representative sample of births in the Oakland, California area. The study features numerous strengths, including a rich array of prospectively collected data beginning in the prenatal period, and archived maternal serum samples, which were stored frozen in nearly all pregnancies. We have previously conducted a follow-up investigation of schizophrenia in this cohort, which has yielded several intriguing findings on the relationship between in utero exposures and risk of that disorder. We aim to: 1) Examine the relationship between in utero infectious and immunologic exposures that can be assayed using archived prenatal serum specimens, and risk of bipolar disorder. These exposures include prenatal influenza and toxoplasmosis infection, and cytokine elevations; 2) examine the relationship between early developmental non-infectious factors and bipolar disorder. These factors include elevated maternal body mass index, maternal smoking and alcohol use, intrauterine growth retardation, and gestational age. 3) Assess pathways that may mediate observed associations between early developmental exposures and risk of bipolar disorder. We shall diagnose cases of bipolar disorder in the cohort using a structured interview, and use both nested case-control and cohort analyses to assess the relationship between the elaborated early developmental exposures and bipolar disorder. These study aims should enable us to identify important causes of bipolar disorder. This would have implications for developing strategies for the prevention of bipolar disorder by elimination or reduction of the identified risk factors, facilitate our understanding of the pathogenesis of bipolar disorder, and ultimately reveal susceptibility genes that interact with the risk factors.