2/2 Harnessing Hormonal Variation to Probe Neural Mechanisms and Optimize CBT Outcomes for OCD

认知行为疗法包括暴露和仪式预防（EX/RP）是一线治疗， 强迫症（OCD）。尽管其有效性，但目前仍不清楚EX/RP如何影响神经系统。 恐惧和焦虑大脑网络的机制，以产生临床改善。此外，数据显示， EX/RP结果在女性中可能更多变。对啮齿动物和健康人的研究表明， (E)影响与恐惧学习、消退和消退保持（恐惧消退）有关的大脑区域 网络）; E也被证明可以增强消退记忆保持。此外，结构和 这些相同的大脑区域的连通性预测OCD治疗结果，包括EX/RP。这些和其他 数据导致的假设，这一合作R 01将开始测试： 高E状态下的强迫症通过增强恐惧的参与来改善消退记忆的保持 灭绝大脑网络，从而获得更好的临床结果。我们还将探讨EX/RP是否引起 灭绝过程在男女之间不同。我们的具体目标是研究：1） 月经周期时相和性别对EX/RP前后预激诱导的神经反应的影响; 2） 月经周期时相和性别对EX/RP结局的影响; 3）强迫症症状改变与 和EX/RP诱导的神经元变化。我们的长期目标是了解性作为一个生物学变量 影响特定的神经过程，因此影响EX/RP治疗结果。为了实现我们的目标，120名成年人 OCD - 80名自然自行车女性和40名男性-将在两个地点招募： 宾夕法尼亚大学（UPenn）和纽约州立精神病研究所/哥伦比亚大学（NYSPI）。通过 此外，纽约大学（NYU）将提供功能磁共振成像范例的专业知识， 作为探索恐惧消退大脑网络的实验工具。研究参与者将完成fMRI 在接收手动EX/RP之前和之后进行扫描。EX/RP方案将包括每日8次（90分钟） 会议包括两次介绍会和六次接触会。女性将被随机分配到 完全EX/RP期间：a）月经开始后的前10天（卵泡早期），当 E水平低;或B）月经周期的第12-22天（卵泡晚期、黄体早期），此时E水平低， 升高。将在多个时间点测量OCD症状和E水平。这种设计将使我们能够 研究月经周期和性别对恐惧消退网络的影响， 关于EX/RP结果。结果将阐明治疗机制，并可能导致个性化治疗 对患有强迫症的女性的建议。

Cognitive behavioral therapy involving exposure and ritual prevention (EX/RP) is a first-line treatment for obsessive compulsive disorder (OCD). Despite its efficacy, it remains unclear how EX/RP influences the neural mechanisms of the fear and anxiety brain networks to yield clinical improvement. Moreover, data indicate that EX/RP outcomes may be more variable in women. Studies in rodents and healthy humans show that estrogen (E) affects the brain regions involved in fear learning, extinction, and extinction retention (the fear extinction network); E also has been shown to enhance extinction memory retention. In addition, the structure and connectivity of these same brain regions predict OCD treatment outcomes, including EX/RP. These and other data lead to the hypothesis that this Collaborative R01 will begin to test: that delivering EX/RP to women with OCD during high E states improves extinction memory retention via enhanced engagement of the fear extinction brain network, resulting in better clinical outcomes. We will also explore whether EX/RP-induced extinction processes differ between women and men. Our specific aims are to examine: 1) the impact of menstrual-cycle phase and sex on extinction-induced neural responses pre and post EX/RP; 2) the impact of menstrual-cycle phase and sex on EX/RP outcome; and 3) the relationship between OCD symptom change and EX/RP-induced neuronal changes. Our long-term goal is to understand how sex as a biological variable affects specific neural processes and hence EX/RP treatment outcomes. To achieve our aims, 120 adults with OCD – 80 natural cycling women and 40 men--will be recruited across two sites: The University of Pennsylvania (UPenn) and the New York State Psychiatric Institute/Columbia University (NYSPI). Through a subcontract, New York University (NYU) will provide expertise in the fMRI imaging paradigm that will be used as an experimental tool to probe the fear extinction brain network. Study participants will complete fMRI scanning before and after receiving manualized EX/RP. The EX/RP protocol will consist of 8 (90 minute) daily sessions comprised of two introductory and six exposure sessions. Women will be randomly assigned to complete EX/RP during either: a) the first 10 days after the start of menstruation (early follicular phase), when E levels are low; or b) days 12-22 of the menstrual cycle (late follicular, early luteal phase), when E levels are elevated. OCD symptoms and E levels will be measured at multiple time points. This design will allow us to study the effects of hormonal variation during the menstrual cycle and sex on the fear extinction network and on EX/RP outcome. The results will elucidate treatment mechanisms and could lead to personalized treatment recommendations for women with OCD.