Risk architecture 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，具有高风险 如果不治疗，可能会导致自杀和杀婴，应作为医疗急救处理。人们普遍认为， 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归类。 因为潜在的神经生物学和风险架构尚不清楚。特别是，目前尚不清楚产后如何 精神病符合躁郁症的范围，因此缺乏预防和治疗指南。长的- 本项目的学期目标是确定产后精神病的独特风险架构。总体目标 在这方面的应用是使用来自瑞典国家登记册的独特的大规模流行病学数据来表征 并比较产后精神病与产后抑郁症、双相情感障碍、 和精神分裂症。我们的中心假设是：(1)产后精神病表现出明显的可加性 遗传效应；以及(2)产后精神病有很高但不完全(不等于一)的遗传相关性 患有躁郁症。其基本原理是，通过了解产后交叉障碍的遗传风险 精神病和相关的障碍，我们更多地了解神经生物学以及如何对这种障碍进行分类。vbl.使用 来自瑞典国家登记册的271,303名母亲的基于家庭的设计和数据，我们将携带 提出以下具体目标：(1)评估产后精神病的家庭风险；(2)量化产后精神病的影响 加性遗传效应对产后精神病风险的影响以及(3)估计产后精神病风险的遗传相关性 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 在五个主要方面的创新：(1)它是围绕着一种基于人口的大型同质资源而建立的，涵盖了 整个国家，最大限度地减少选择偏见；到目前为止，研究为产后的熟悉性提供了证据 精神病，但这些研究主要集中在探索是否存在家族关系 产后精神病和其他精神障碍，通过采访先证者。它们不包括控制和， 因此，我们无法提供相对于一般人群和这些研究的风险估计 没有探索跨障碍的熟悉性；(2)将瑞典基于人口的登记联系起来提供了一个独特的 确定具体风险影响的机会，如母亲怀孕年龄、精神病史、 社会经济因素和既往出生情况；(3)本研究运用前沿生存分析方法研究 考虑审查的加性遗传学的新方面；(4)所提出的模型提供了 对产后精神病的具体危险因素的估计，而不是遗传混淆；以及(5)它提供了一个 了解产后精神病和双相情感障碍产后共同风险的新框架 抑郁症和精神分裂症。我们的方法是一种新的方法，与其他方法相比有很大不同 研究并将使我们能够克服对加性遗传效应和遗传相关性建模的挑战， 从而为了解产后精神病的风险状况开辟了新的视野。

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.