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: 10052122
• 负责人: EDNA B FOA
• 金额: $ 70.07万
• 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/10052122
• 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.

包括暴露和仪式预防在内的认知行为疗法（EX/RP）是治疗糖尿病的一线方法