Multi-target repetitive Transcranial Magnetic Stimulation (rTMS) treatment for Major Depressive Disorder (MDD) and comorbid pain

多靶点重复经颅磁刺激 (rTMS) 治疗重度抑郁症 (MDD) 和共病疼痛

• 批准号: 10302189
• 负责人: Juliana Corlier
• 金额: $ 18.29万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-04 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10302189
• 关键词: Affect; Analgesics; Antidepressive Agents; Award; Brain; Brief Pain Inventory; Clinical; Data; Data Set; Disease remission; Down-Regulation; Fibromyalgia; Functional Magnetic Resonance Imaging; Hamilton Rating Scale for Depression; Joints; Left; Link; Machine Learning; Major Depressive Disorder; Mediating; Mediation; Mental Depression; Mentors; Modeling; Mood Disorders; Motor Cortex; Multimodal Imaging; Outcome; Output; Pain; Pain Disorder; Pain management; Pathogenesis; Pathway interactions; Patients; Pattern; Pharmacological Treatment; Pharmacology; Prefrontal Cortex; Procedures; Protocols documentation; Quality of life; Randomized; Regulation; Research; Research Personnel; Resistance; Severities; Site; Symptoms; Syndrome; Techniques; Testing; Therapeutic Effect; Training; Treatment Efficacy; Treatment Protocols; Treatment outcome; Unemployment; antidepressant effect; associated symptom; career; central pain; chronic pain; comorbidity; depressive symptoms; disability; effectiveness evaluation; efficacy testing; fibromyalgia patients; functional MRI scan; improved; innovation; mood symptom; neuroimaging; neuromechanism; neuropsychiatry; neuroregulation; novel; novel strategies; opioid use disorder; pain processing; pain relief; pain symptom; painful neuropathy; patient subsets; primary outcome; random forest; rate of change; relating to nervous system; repetitive transcranial magnetic stimulation; response; sham-controlled study; supervised learning; support vector machine; treatment effect; treatment group

PROJECT SUMMARY Major Depressive Disorder (MDD) and fibromyalgia (FM) are highly comorbid, disabling and resistant to treatment. More than half of MDD patients present with pain symptoms, and the comorbidity is associated with reduced quality of life, poor pharmacological treatment outcomes, and opioid use disorders. New approaches to help comorbid patients are urgently needed. Repetitive Transcranial Magnetic Stimulation (rTMS) treatment may ameliorate both pain and mood symptoms, possibly through modulation of shared underlying pathophysiological brain networks. Preliminary data indicate rTMS applied to the left dorsolateral prefrontal cortex (lDLPFC) significantly improved both depressive and moderate pain symptoms but failed to improve more severe comorbid pain. In this application, we propose to test the efficacy of a multi-target rTMS protocol that may be more successful in treating both mood and pain symptoms in comorbid MDD/FM. This includes two complementary objectives: 1) to test the effects of a novel rTMS protocol for comorbid MDD and FM, and 2) to provide critical additional training to the candidate that will facilitate her transition into independence as a researcher specializing in the comorbidity of mood disorders with chronic pain and their treatment with rTMS. This will be achieved through a randomized, sham-controlled study with two experimental conditions: A) Active rTMS to lDLPFC (established target for MDD) and sham rTMS to the primary motor cortex (M1, established pain target); and B) Active rTMS to both, lDLPFC and M1. We anticipate that multi-site rTMS will be more efficacious to treat both MDD and FM symptoms than the single site rTMS protocol. Additionally, we will determine the differences and similarities of neural signatures of MDD and FM and how these interact in the comorbid condition using machine learning techniques. The K01 project will take place at UCLA with the mentoring support from the director of the Neuromodulation Division, two co-mentors and four other collaborators with expertise in rTMS, depression, chronic pain, multimodal imaging, and machine learning analysis. This approach will achieve the project’s specific aims to: 1. Evaluate the effect of multi-site vs. single site rTMS on clinical symptoms; 2. Determine the interaction of networks affected in MDD and chronic pain and how they are modulated by rTMS; and 3. Examine the interaction between analgesic and antidepressant effects of rTMS. If these aims are achieved, the short-term outcome of this project will help determine the efficacy of multi-site rTMS for comorbid MDD and FM, identify the overlap of the neural signature of MDD and FM and how it is modulated by rTMS, and characterize the relationship between rTMS-induced antidepressant and analgesic effects. In the long-term, current rTMS procedures may be significantly improved for the treatment of MDD with comorbid chronic pain.

项目总结 严重抑郁障碍(MDD)和纤维肌痛(FM)高度并存、致残和抵抗 治疗。超过一半的MDD患者出现疼痛症状，并且共病与 生活质量下降，药物治疗结果不佳，以及阿片类药物使用障碍。以新的方式 迫切需要帮助并存的病人。重复经颅磁刺激(RTMS)治疗可以 改善疼痛和情绪症状，可能是通过调节共同的潜在病理生理 大脑网络。 初步数据显示，rTMS应用于左侧背外侧前额叶皮质(LDLPFC)显著改善 抑郁和中度疼痛症状，但未能改善更严重的并存疼痛。在这 我们建议测试一种可能在治疗方面更成功的多靶点rTMS方案的疗效。 MDD/FM共病有情绪和疼痛两种症状。这包括两个相辅相成的目标：1)测试 一种新的治疗MDD和FM并存的rTMS方案的效果，以及2)为 这位候选人将帮助她过渡到独立的状态，成为一名专门研究 慢性疼痛的情绪障碍及其rTMS的治疗。这将通过随机的、 两种实验条件下的假对照研究：a)激活rTMS至lDLPFC(MDD的已建立靶点) 和假rTMS到初级运动皮质(M1，已建立的疼痛靶点)；以及B)主动rTMS到两者，lDLPFC 和M1。我们预计多部位rTMS在治疗MDD和FM症状方面将比 单站点RTMS协议。此外，我们将确定神经信号的不同和相似之处 使用机器学习技术，了解MDD和FM在共存条件下如何相互作用。 K01项目将在加州大学洛杉矶分校进行，并得到神经调节主任的指导支持 部门、两名共同导师和其他四名合作者，他们在rTMS、抑郁症、慢性疼痛、 多模式成像和机器学习分析。这种方式将实现项目的具体目标：1. 评价多部位rTMS与单部位rTMS对临床症状的影响；2.确定 MDD和慢性疼痛中受影响的网络以及rTMS如何调节它们；以及3.检查相互作用 RTMS的镇痛和抗抑郁作用之间的关系。如果实现这些目标，短期结果将是 该项目将有助于确定多部位rTMS对MDD和FM共病的疗效，确定 MDD和FM的神经特征及其如何被rTMS调制，并表征两者之间的关系 RTMS的抗抑郁和镇痛作用。从长远来看，目前的rTMS程序可能是 对伴有慢性疼痛的MDD的治疗有显著改善。