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: 10600978
• 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/10600978
• 关键词: Affect; Analgesics; Antidepressive Agents; Award; Brain; Brief Pain Inventory; Classification; 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; Neuronavigation; Outcome; Output; Pain; Pain Disorder; Pain management; Pathogenesis; Pathway interactions; Patients; Pattern; Pharmacological Treatment; 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 evaluation; efficacy testing; fibromyalgia patients; functional MRI scan; improved; innovation; mood symptom; neural; neuroimaging; neuromechanism; neuropsychiatry; neuroregulation; novel; novel strategies; opioid use disorder; pain processing; pain relief; pain symptom; painful neuropathy; patient subsets; pharmacologic; primary outcome; random forest; rate of change; 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.

项目概要 重度抑郁症 (MDD) 和纤维肌痛 (FM) 具有高度共病性、致残性和耐药性 超过一半的 MDD 患者会出现疼痛症状，并且其合并症与治疗有关。 生活质量下降、药物治疗效果不佳以及阿片类药物使用障碍的新方法。 可能迫切需要重复经颅磁刺激（rTMS）治疗来帮助合并症患者。 可能通过调节共同的潜在病理生理学来改善疼痛和情绪症状 大脑网络。 初步数据表明，应用于左背外侧前额叶皮层 (IDLPFC) 的 rTMS 显着改善 抑郁和中度疼痛症状，但未能改善更严重的共病疼痛。 应用程序中，我们建议测试多目标 rTMS 方案的功效，该方案可能会更成功地治疗 共病 MDD/FM 中的情绪和疼痛症状 这包括两个互补的目标：1) 测试 新型 rTMS 方案对 MDD 和 FM 共病的影响，以及 2) 为患者提供关键的额外培训 候选人将有助于她作为一名专门研究合并症的研究员过渡到独立 伴有慢性疼痛的情绪障碍及其 rTMS 治疗 这将通过随机、、 具有两种实验条件的假对照研究：A) 针对 lDLPFC 的主动 rTMS（MDD 既定目标） B) 对初级运动皮层（M1，既定疼痛目标）进行假 rTMS；以及对 lDLPFC 进行主动 rTMS； 我们预计多部位 rTMS 比治疗 MDD 和 FM 症状更有效。 此外，我们将确定单站点 rTMS 协议的神经特征的差异和相似之处。 MDD 和 FM 的关系，以及它们如何使用机器学习技术在共病条件下相互作用。 K01 项目将在 UCLA 进行，并得到神经调节主任的指导支持 该部门的两名共同导师和四名其他合作者在 rTMS、抑郁症、慢性疼痛、 该方法将实现该项目的具体目标：1. 评估多部位与单部位 rTMS 对临床症状的影响 2. 确定以下因素的相互作用； MDD 和慢性疼痛影响的网络以及 rTMS 如何调节它们；以及 3. 检查相互作用； 如果这些目标得以实现，则 rTMS 的镇痛和抗抑郁作用之间的关系。 该项目将帮助确定多站点 rTMS 对共病 MDD 和 FM 的疗效，确定两者的重叠 MDD 和 FM 的神经特征及其如何通过 rTMS 进行调制，并表征两者之间的关系 从长远来看，当前的 rTMS 程序可能会产生抗抑郁和镇痛作用。 显着改善 MDD 合并慢性疼痛的治疗。

项目成果

Pretreatment pupillary reactivity is associated with differential early response to 10 Hz and intermittent theta-burst repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD).

治疗前瞳孔反应性与重度抑郁症 (MDD) 的 10 Hz 和间歇性 θ 突发重复经颅磁刺激 (rTMS) 治疗的早期反应差异相关。

• 发表时间: 2023
• 影响因子: 7.7
• 作者: Citrenbaum, Cole;Corlier, Juliana;Ngo, Doan;Vince;Wilson, Andrew;Wilke, Scott A;Krantz, David;Tadayonnejad, Reza;Ginder, Nathaniel;Levitt, Jennifer;Lee, John H;Leuchter, Michael K;Strouse, Thomas B;Corse, Andrew;Vyas, Pooja;Leu
• 通讯作者: Leu