Risk architecture of postpartum psychosis

产后精神病的风险结构

基本信息

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
项目类别：
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

项目摘要

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，是最严重的精神病病之一，风险很高如果未经治疗，则自杀和杀婴，应视为医疗紧急情况。通常认为双极谱障碍障碍，但是这种疾病尚未在当前疾病分类系统中分类因为基本的神经生物学和风险架构尚不清楚。特别是，未知产后如何精神病符合双极光谱，因此缺乏预防和治疗指南。长期该项目的术语目标是确定产后精神病的独特风险结构。总体目标在此应用程序中，是使用瑞典国家注册表的独特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，躁郁症，和精神分裂症。我们的中心假设是：（1）产后精神病显示添加剂的重要证据遗传作用；（2）产后精神病具有较高但不完全（不等于一个）遗传相关性躁郁症。理由是，通过了解产后的跨点遗传风险精神病和相关疾病，我们更多地了解神经生物学以及如何对这种疾病进行分类。使用来自瑞典国家登记册的271,303位母亲的基于家庭的设计和数据，我们将携带提出以下具体目的：（1）评估产后精神病的家族风险；（2）量化加性遗传对产后精神病风险的影响，（3）估计产后精神病，躁郁症，产后抑郁症和精神分裂症。拟议的研究是在五个主要领域的创新性：（1）它围绕着大量基于人群的资源，涵盖了整个国家，最大程度地减少选择偏见；迄今为止的研究为产后家族性提供了证据精神病，但这些研究主要集中于探索是否存在家族关联产后精神病和其他精神障碍通过采访概率。他们不包括控件，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家族性；（2）链接基于瑞典人口的登记册提供了独特的确定特定风险影响的机会，例如母亲在怀孕时期，精神病史，社会经济因素和先前的出生；（3）研究使用最先进的生存分析方法来研究考虑到审查的同时，加性遗传学的新颖方面；（4）提议的模型提供了对产后精神病的特定危险因素的估计超出了遗传混淆；（5）它提供了理解产后精神病和躁郁症的新型框架，产后抑郁症和精神分裂症。与其他相比，我们的方法是一种新的且实质上不同的方法研究，将使我们能够克服建模添加剂遗传效应和遗传相关性的挑战，从而为理解产后精神病的风险概况开辟了新的视野。