Risk architecture of postpartum psychosis

产后精神病的风险结构

• 批准号: 10575003
• 负责人: Behrang Mahjani
• 金额: $ 25.35万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-15 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10575003
• 关键词: Affect; Age; Architecture; Area; Bipolar Disorder; Birth; Childbirth; Classification; Clinical; Computing Methodologies; Data; Diagnosis; Diagnostic; Disease; Environment; Environmental Risk Factor; Etiology; Family; Family Relationship; Family history of; Family member; First Degree Relative; General Population; Generations; Genetic; Genetic Diseases; Genetic Predisposition to Disease; Genetic Risk; Goals; Heritability; Infanticide; Intercept; Interview; Link; Manic; Maternal Age; Measures; Medical emergency; Mental Depression; Mental disorders; Methods; Mission; Modeling; Mood Disorders; Mothers; Neurobehavioral Manifestations; Neurobiology; Orphan; Outcome; Parents; Phenotype; Population; Positioning Attribute; Postpartum Depression; Postpartum Period; Pregnancy; Pregnant Women; Prevalence; Prevention Guidelines; Psychoses; Psychotic Disorders; Public Health; Quantitative Genetics; Rare Diseases; Recording of previous events; Recurrence; Registries; Relative Risks; Research; Research Personnel; Resources; Risk; Risk Estimate; Risk Factors; Schizophrenia; Selection Bias; Siblings; Socioeconomic Factors; Source; Statistical Methods; Survival Analysis; Sweden; System; Time; United States National Institutes of Health; age effect; bipolar spectrum; cohort; design; disease classification; epidemiologic data; genetic pedigree; genetic risk factor; high risk; innovation; insight; mood symptom; novel; population based; proband; prognostic; psychosis risk; psychotic symptoms; risk sharing; severe mental illness; suicidal risk; treatment guidelines

Postpartum psychosis is a severe mood disorder, one of the most severe psychiatric conditions, with high risks of suicide and infanticide if untreated, and should be treated as a medical emergency. It is generally considered a bipolar spectrum disorder, yet, this disorder has not been classified in current disease classification systems because the underlying neurobiology and risk architecture is unclear. In particular, it is unknown how postpartum psychosis fits within the bipolar spectrum, and thus prevention and treatment guidelines are lacking. The long- term goal of this project is to identify the distinct risk architecture of postpartum psychosis. The overall objectives in this application is to use unique large epidemiological data from the Swedish national registers to characterize and compare the genetic risk architecture of postpartum psychosis with postpartum depression, bipolar disorder, and schizophrenia. Our central hypotheses are: (1) postpartum psychosis shows significant evidence of additive genetic effects; and (2) postpartum psychosis has a high but not complete (not equal to one) genetic correlation with bipolar disorder. The rationale is that by understanding the cross-disorder genetic risk of postpartum psychosis and related disorders, we know more about the neurobiology and how to classify this disorder. Using family-based designs and data for a cohort of 271,303 mothers from the Swedish national registers, we will carry out the following Specific Aims: (1) evaluate the familial risk of postpartum psychosis; (2) quantify the impact of additive genetic effects on risk of postpartum psychosis and (3) estimate the genetic correlation between postpartum psychosis, bipolar disorder, postpartum depression, and schizophrenia. The proposed research is innovative in five main areas: (1) it is built around a large homogeneous population-based resource covering an entire nation, minimizing selection bias; Studies thus far provide evidence for the familiality of postpartum psychosis, but these studies have mainly focused on exploring if there is a familial association between postpartum psychosis and other mental disorders by interviewing probands. They did not include controls and, therefore, were not able to provide an estimate of the risk relative to the general population and these studies did not explore familiality across disorders; (2) linking the Swedish population-based register provides a unique opportunity to determine specific risk effects, such as mother's age at pregnancy, psychiatric history, socioeconomic factors, and previous births; (3) the study uses cutting-edge survival analysis methods to study novel aspects of additive genetics while taking into account censoring; (4) the proposed model delivers the estimates of the specific risk factors for postpartum psychosis beyond genetic confounding; and (5) it provides a novel framework for understanding shared risk across postpartum psychosis and bipolar disorder, postpartum depression, and schizophrenia. Our approach is a new and substantially different approach compared to other studies and will allow us to overcome the challenges of modeling additive genetic effects and genetic correlation, thereby opening new horizons for understanding the risk profile of postpartum psychosis.

产后精神病是一种严重的情绪障碍，是最严重的精神疾病之一，风险很高 如果不治疗，会有自杀和自杀的危险，应该作为医疗紧急情况处理。一般认为 一种双相谱系障碍，然而，这种障碍在目前的疾病分类系统中还没有被分类 因为潜在的神经生物学和风险结构尚不清楚。尤其是产后 精神病属于双相型，因此缺乏预防和治疗指南。很长的- 这个项目的长期目标是确定产后精神病的独特风险结构。总体目标 使用瑞典国家登记处的独特的大型流行病学数据来表征 并将产后精神病的遗传风险结构与产后抑郁症，双相情感障碍， 和精神分裂症我们的中心假设是：（1）产后精神病显示出明显的叠加证据， 遗传效应;（2）产后精神病具有高度但不完全（不等于1）的遗传相关性 患有躁郁症。其基本原理是，通过了解产后交叉疾病的遗传风险， 精神病和相关疾病，我们知道更多关于神经生物学和如何分类这种疾病。使用 基于家庭的设计和来自瑞典国家登记册的271，303名母亲的队列数据，我们将携带 具体目的如下：（1）评估产后精神病的家族风险;（2）量化产后精神病的影响， 产后精神病风险的加性遗传效应和（3）估计 产后精神病、双相情感障碍、产后抑郁症和精神分裂症。拟议的研究是 创新的五个主要领域：（1）它是建立在一个大型同质人口为基础的资源， 整个国家，最大限度地减少选择偏差;迄今为止的研究提供了产后家庭的证据， 精神病，但这些研究主要集中在探索是否有一个家庭之间的联系， 产后精神病和其他精神障碍的调查。它们不包括对照组， 因此，无法提供相对于一般人群的风险估计，这些研究 没有探索跨疾病的熟悉性;（2）将瑞典基于人口的登记册联系起来提供了一个独特的 确定特定风险影响的机会，如母亲怀孕时的年龄，精神病史， 社会经济因素和以前的出生;（3）该研究使用尖端的生存分析方法来研究 添加剂遗传学的新方面，同时考虑到审查;（4）所提出的模型提供了 估计产后精神病的特定危险因素，除了遗传混杂;（5）它提供了一个 了解产后精神病和双相情感障碍共有风险的新框架，产后 抑郁症和精神分裂症我们的方法是一种新的，与其他方法相比有很大不同的方法。 研究，并将使我们能够克服建模加性遗传效应和遗传相关性的挑战， 从而为了解产后精神病的风险状况开辟了新的视野。