Prenatal Factors and Risk of Bipolar Disorder

描述（由申请人提供）：在本次调查中，产前因素和双相情感障碍（PFB）项目，我们将研究早期发育侮辱与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育危险因素，并评估这些因素是否对精神分裂症有特异性。为此，我们将利用儿童健康与发展研究的出生队列，这是加利福尼亚州奥克兰地区的一个庞大而具有代表性的出生样本。这项研究有很多优势，包括从产前开始收集的丰富的前瞻性数据，以及存档的母亲血清样本，这些样本几乎在所有怀孕期间都被冷冻保存。我们之前在这个队列中进行了一项精神分裂症的随访调查，在子宫内暴露与该疾病风险之间的关系方面产生了一些有趣的发现。我们的目标是：1)检查子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标本进行检测，以及双相情感障碍的风险。这些暴露包括产前流感和弓形虫感染，以及细胞因子升高；2)探讨早期发育非感染性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、宫内发育迟缓和胎龄。3)评估可能介导观察到的早期发育暴露与双相情感障碍风险之间关联的途径。我们将使用结构化访谈来诊断队列中的双相情感障碍病例，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。这将对通过消除或减少已确定的危险因素来制定预防双相情感障碍的策略产生影响，促进我们对双相情感障碍发病机制的理解，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.