Impact of genetic markers, early life experience, & life stress on IC/PBS symptom

间质性膀胱炎/膀胱疼痛综合征（IC/PBS）是一种常见的慢性膀胱综合征， 膀胱疼痛和不适（尿急）和排尿频率增加。与其相关联 健康相关生活质量（HRQOL）、生产力显著下降，医疗费用增加。 越来越多的证据表明，IC/PBS与其他慢性功能性疼痛障碍有几个共同特征 如肠易激综合征（IBS）和纤维肌痛，包括不良早期生活事件史， 症状发作或加重前的心理或身体压力，以及焦虑的存在 和/或抑郁症和糟糕的疾病应对。这些发现表明IC/PBS发展的模型， 包括脆弱性因素的童年创伤相互作用与生活压力，家庭建模，和穷人 应对这些因素最有可能与遗传脆弱性相互作用，既为中央和外围风险 （包括情感失调）以及膀胱疾病史。 拟议的项目遵循加州大学洛杉矶分校MAPP中心的总体主题，使用有针对性的流行病学 研究IC/PBS症状的调节剂和介质以及1年内症状影响的方法 在不同的男性和女性患者中。在目标1中，我们将每两个月检查一次IC/PBS患者，持续1 年，以描述患者的严重程度、频率和主要症状的变化，HRQOL， 生产力和医疗保健利用率。我们将检查症状表现的并发介质 包括压力、应对方式和特定的焦虑。在目标2中，我们将研究生命早期的脆弱性 包括遗传特征、早期生活创伤和家族模型在内的因素作为模型中的调节变量， 检验这些因素与成人症状表现（包括合并症）相关的重要假设 情感性和其他功能性疼痛障碍以及对中介变量的反应。在aim中 3，我们将对IBS患者样本应用相同的建模来检验相似介质 和调节剂在其他功能性疼痛障碍中起作用，包括遗传和早期生命脆弱性， 持续的压力源该项目的其他重要成果将是开发一个IC/PBS， 特定焦虑的测量，与模型预测因子相关的治疗反应数据， 在一段时间内症状变化的新数据。如果验证了IC/PBS的拟定模型， 症状的发展对于更好地理解潜在机制具有重要意义， 以及更有效的治疗策略。

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a common chronic bladder syndrome characterized by bladder pain and discomfort (urgency) and increased frequency of urination. It is associated with significant decrements in health-related quality of life (HRQOL), productivity and increased healthcare costs. There is growing evidence that IC/PBS shares several features with other chronic functional pain disorders like irritable bowel syndrome (IBS) and fibromyalgia, including a history of adverse early life events, a history psychological or physical stressors preceding symptom onset or exacerbation, and the presence of anxiety and/or depression and poor illness coping. These findings suggest a model of IC/PBS development that includes vulnerability factors of childhood trauma interacting with life stress, familial modeling, and poor coping. These factors most likely interact with genetic vulnerabilities for both central and peripheral risk (including affective dysregulation) as well as bladder disease history. The proposed project follows the overall themes for the UCLA MAPP Center using a targeted epidemiology approach to study moderators and mediators of IC/PBS symptoms and symptom impact over a 1-year period in a diverse group of male and female patients. In Aim 1 we will examine IC/PBS patients bi-monthly for 1 year to characterize patients in terms of severity, frequency, and variation in cardinal symptoms, HRQOL, productivity, and healthcare utilization. We will examine concurrent mediators of symptom presentation including stress, coping and symptom-specific anxiety. In Aim 2, we will examine early life vulnerability factors including genetic traits, early life trauma, and familial modeling as moderator variables in the model to test the important hypotheses that these factors are related to adult symptom presentation including comorbidities with affective and other functional pain disorders and response to the mediating variables. In Aim 3, we will apply the same modeling to a sample of IBS patients to test the hypothesis that similar mediators and moderators operate in other functional pain disorders including genetic and early life vulnerabilities and ongoing stressors. Other important outcomes from this project will be the development of a IC/PBS targeted measure of symptom-specific anxiety, data on treatment response as related to the model predictors and new data on symptom variation over an extended period of time. If verified the proposed model of IC/PBS symptom development has important implications for a better understanding of underlying mechanisms as well as for more effective treatment strategies.