Bipolar Disorder in Pregnancy: Predictors of Mobidity

说明(申请人提供)：尽管双相情感障碍(BPD)的发病率很高，而且在育龄期间发病率很高，但人们对女性生殖生命周期对BPD的影响知之甚少。临床医生缺乏针对BPD围产期管理的循证指南。该提案针对的是一个研究不足的领域，对美国每年约10万名患有BPD的女性造成了相当大的公共健康影响。 该项目的主要目标是描述临床、心理社会因素，特别是孕期BPD复发的药理学预测因素。初步研究结果表明，治疗不当是产前BPD复发的一个特别有力的预测因子。因此，将特别强调调查因停药或因产前清除增加而导致药物浓度下降而发生的次优药物治疗相关的复发风险。一项前瞻性队列设计和每月评估将在美国两个领先的围产期精神病学学术中心之间的合作调查中实施，这些学术中心在怀孕期间情绪障碍研究方面具有特定专业知识。其具体目标是1)量化与次优药物治疗相关的综合征和亚综合征产前BPD疾病的风险，同时控制以前病程的严重性和最近的心理社会应激源，2)检查产妇产前BPD发病率和精神药物暴露与婴儿分娩结局的关系，从而填补目前的空白，完善临床风险/益处评估的必要方面，以及3)进行药代动力学(PK)建模，努力描绘与妊娠相关的药物清除变化，并提供对胎儿药物暴露的初步可靠估计。 研究结果将是一个渐进的进步：1)阐明妊娠期BPD发病率的风险因素；2)提供临床相关数据，以制定妊娠期BPD的治疗指南；3)作为旨在优化母婴结局的预防战略的基础。此外，新的PK数据将扩大我们对产前药物代谢的理解，该项目将建立一组患有BPD的妇女的孩子，并具有详细的前瞻性产前病史。

DESCRIPTION (provided by applicant): Despite the significant morbidity of bipolar disorder (BPD) and its high prevalence during the childbearing years, remarkably little is known about the impact of the female reproductive life cycle on BPD. Clinicians lack evidence-based guidelines for the perinatal management of BPD. The proposal addresses an understudied area with considerable public health implications for the estimated 100,000 women with BPD who conceive each year in the US. The broad goal of this project is to delineate the clinical, psychosocial, and in particular, pharmacologic predictors of BPD recurrence during pregnancy. Preliminary findings suggest that inadequate treatment is a particularly robust predictor of prenatal BPD recurrence. Consequently, a specific emphasis will be placed on investigating the recurrence risk associated with suboptimal pharmacotherapy occurring as a result of medication discontinuation or declining drug concentrations secondary to increased prenatal clearance. A prospective cohort design with monthly assessments will be implemented in a collaborative investigation between two of the leading perinatal psychiatry academic centers in the US with specific expertise in mood disorders research during pregnancy. The specific aims are 1) to quantify the risks for both syndromal and subsyndromal prenatal BPD illness associated with suboptimal pharmacotherapy while controlling for the severity of the previous course of illness and recent psychosocial stressors, 2) to examine the association of maternal prenatal BPD morbidity and psychotropic exposure with infant outcome at delivery thereby filling a current void and rounding out the requisite facets of the clinical risk/benefit assessment, and 3) to conduct pharmacokinetic (PK) modeling in an effort to delineate pregnancy-associated changes in drug clearance and provide initial reliable estimates of fetal drug exposure. Study results will represent an incremental advance that: 1) elucidates risk factors for BPD morbidity during pregnancy; 2) contributes clinically relevant data to establish therapeutic guidelines for BPD during pregnancy; and 3) serve as a basis for preventive strategies aimed at optimizing maternal and infant outcome. Furthermore, the novel PK data will expand our understanding of prenatal drug metabolism, and the project will establish a cohort of children of women with BPD with detailed prospective prenatal histories.