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

2/2 利用荷尔蒙变化来探索神经机制并优化强迫症的 CBT 结果

• 批准号: 10477932
• 负责人: EDNA B FOA
• 金额: $ 67.99万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10477932
• 关键词: Adult; Affect; Aftercare; Amygdaloid structure; Anterior; Anxiety; Biological; Biological Assay; Blood; Brain; Brain region; Clinical; Cognitive Therapy; Data; Dorsal; Elements; Ensure; Estrogens; Exhibits; Exposure to; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; Goals; Gonadal Hormones; Hippocampus (Brain); Hormonal; Hormones; Human; Image; Individual; Institutes; Knowledge; Lead; Luteal Phase; Measures; Mediating; Menstrual cycle; Menstruation; Neurons; New York; Obsessive-Compulsive Disorder; Outcome; Participant; Patients; Pennsylvania; Phase; Prefrontal Cortex; Prevention; Prevention Protocols; Process; Protocols documentation; Randomized; Recommendation; Research; Rest; Ritual compulsion; Rodent; Sample Size; Sampling; Scanning; Severities; Sex Differences; Signal Transduction; Site; Structure; Symptoms; Testing; Time; Treatment Protocols; Treatment outcome; Universities; Variant; Woman; blood oxygen level dependent; cingulate cortex; conditioned fear; design; follow-up; functional MRI scan; improved; indexing; learning extinction; memory retention; men; neuromechanism; outcome prediction; personalized medicine; predicting response; proliferative phase Menstrual cycle; recruit; reduce symptoms; relating to nervous system; response; severe mental illness; sex; sex cycle; tool

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.

认知行为疗法涉及暴露和仪式预防（EX/RP）是一种一线治疗方法 强迫症（OCD）。尽管有效率，但尚不清楚EX/RP如何影响中性 恐惧和动画大脑网络的机制可产生临床改善。此外，数据表明 妇女的EX/RP结果可能会更可变。啮齿动物和健康人的研究表明雌激素 （e）影响恐惧学习，扩展和扩展保留涉及的大脑区域（恐惧扩展 网络）; E还显示E可以增强扩展记忆的保留。另外，结构和 这些相同大脑区域的连通性预测了OCD治疗结果，包括EX/RP。这些和其他 数据导致了这样的假设：该协作R01将开始测试：将EX/RP交付给患有 高E状态期间的强迫症通过增强恐惧的参与来改善扩展记忆的保留 扩展大脑网络，导致更好的临床结局。我们还将探讨是否诱导EX/RP 男女之间的扩展过程不同。我们的具体目的是检查：1） 月经周期的阶段和性别在延伸诱导的神经反应前和后RP； 2） 月经周期阶段和性别的性别/RP结果； 3）强迫症症状改变之间的关系 和EX/RP诱导的神经元变化。我们的长期目标是了解性别如何作为生物变量 影响特定的神经过程，因此会影响/RP治疗结果。为了实现我们的目标，有120名成年人 强迫症 - 80名自然自行车妇女和40名男性 - 将在两个地点招募： 宾夕法尼亚州（UPENN）和纽约州精神病学院/哥伦比亚大学（NYSPI）。通过一个 分包合同，纽约大学（NYU）将提供FMRI成像范式的专业知识 作为探测恐惧扩展大脑网络的实验工具。学习参与者将完成fMRI 在接收手动的EX/RP之前和之后进行扫描。 EX/RP协议将每天8（90分钟）组成 会议完成了两个介绍和六次曝光会议。妇女将被随机分配给 在任何一个期间完成EX/RP：a）月经开始后的前10天（早期卵泡阶段），当 E水平很低；或b）月经周期的第12-22天（晚期卵泡早期，早期的黄体期），当E水平为 高架。 OCD符号和E级将在多个时间点测量。这种设计将使我们能够 研究月经周期和性别对恐惧扩展网络的影响和性别的影响 在EX/RP结果上。结果将阐明治疗机制，并可能导致个性化治疗 针对强迫症女性的建议。