1/2 Harnessing Hormonal Variation to Probe Neural Mechanisms and Optimize CBT Outcomes for OCD

涉及暴露和仪式预防的认知行为疗法(EX/RP)是治疗 强迫症(OCD)。尽管EX/RP有效，但它如何影响神经仍不清楚。 恐惧和焦虑的大脑网络产生临床改善的机制。此外，数据表明， 在女性中，EX/RP的结果可能更具变异性。对啮齿动物和健康人的研究表明，雌激素 (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也被证明能增强消光记忆的保持。此外，该结构和 这些脑区的连通性可以预测强迫症的治疗结果，包括EX/RP。这些和其他 数据导致了这样的假设，即这款Collaborative R01将开始测试：为患有以下疾病的女性提供EX/RP 高E状态下的强迫症通过增强对恐惧的参与来改善消退记忆保持 消除脑网络，导致更好的临床结果。我们还将探讨EX/RP诱导的 灭绝的过程在女性和男性之间是不同的。我们的具体目标是检查：1)影响 月经周期阶段和性别对绝经前、后绝育诱导的神经反应的影响 月经周期阶段和性别对EX/RP结局的影响；3)强迫症症状变化的关系 以及EX/RP引起的神经元改变。我们的长期目标是了解作为生物变量的性行为 影响特定的神经过程，从而影响EX/RP治疗结果。为了实现我们的目标，120名成年人 OCD--80名自然骑自行车的女性和40名男性--将在两个地点招募： 宾夕法尼亚大学(UPenn)和纽约州精神病研究所/哥伦比亚大学(NYSPI)。通过一个 分包合同，纽约大学(NYU)将提供将使用的功能磁共振成像范例方面的专业知识 作为探索恐惧消退大脑网络的实验工具。研究参与者将完成功能磁共振成像 在收到手动EX/RP之前和之后进行扫描。EX/RP协议由每天8次(90分钟)组成 会议由两次介绍性会议和六次公开会议组成。女性将被随机分配到 在以下任一期间完成EX/RP：a)月经开始后10天(卵泡早期) 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水平为 抬高了。强迫症症状和E水平将在多个时间点进行测量。这种设计将使我们能够 研究月经周期中荷尔蒙的变化和性别对恐惧消退网络和 关于EX/RP的结果。这一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.