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

间质性膀胱炎/疼痛膀胱综合征(IC/PBS)是一种常见的慢性膀胱综合征 由于膀胱疼痛和不适(紧迫感)和尿频增加。它与以下内容关联 与健康相关的生活质量(HRQOL)、生产力显著下降，医疗成本增加。 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点 如肠易激综合征(IBS)和纤维肌痛，包括不良早期生活事件史， 症状出现或加重之前的心理或身体压力因素，以及焦虑的存在 和/或抑郁和糟糕的疾病应对能力。这些发现提出了IC/PBS发展的模型 包括童年创伤与生活压力相互作用、家族性建模和贫困的易感性因素 应对。这些因素很可能与中心风险和外围风险的遗传脆弱性相互作用 (包括情感性失调)以及膀胱病史。 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 一年研究IC/PBS症状和症状影响的调节因子和中介因子的方法 在一组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 一年，根据患者的严重程度、频率和主要症状、HRQOL、 工作效率和医疗保健利用率。我们将检查同时存在的症状表现的中介者 包括压力、应对和特定症状的焦虑。在目标2中，我们将研究早期生命的脆弱性 包括遗传特征、早期生活创伤和家庭建模在内的因素作为模型中的调节变量 测试这些因素与成人症状表现相关的重要假设，包括合并症 情感和其他功能性疼痛障碍以及对中介变量的反应。在AIM 3，我们将对IBS患者的样本应用相同的模型来检验相似的介体的假设 和调节剂在其他功能性疼痛障碍中发挥作用，包括遗传和早期生命脆弱性和 持续的压力源。该项目的其他重要成果将是开发有针对性的IC/PBS 症状特定焦虑的测量，与模型预测因素和治疗反应相关的数据 关于较长时间内症状变化的新数据。如果验证了所提出的IC/PBS模型 症状的发展对于更好地理解潜在的机制具有重要的意义 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.