Efficacy of biomarker-guided rTMS for treatment resistant depression

生物标志物引导的 rTMS 对难治性抑郁症的疗效

• 批准号: 10633055
• 负责人: Faith M Gunning
• 金额: $ 130.71万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-05 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633055
• 关键词: Accounting; Aftercare; Amygdaloid structure; Anatomy; Anhedonia; Antidepressive Agents; Anxiety; Area; Arousal; Behavior assessment; Biological Markers; Brain; Brain scan; Clinical; Clinical assessments; Corpus striatum structure; Data; Diagnosis; Diagnostic; Dimensions; Disease remission; Exhibits; Fiber; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Heterogeneity; Individual; Individual Differences; Intervention; Left; Major Depressive Disorder; Maps; Measures; Medical; Mental Depression; Methods; Modeling; Motivation; Patients; Pattern; Pharmacotherapy; Prediction of Response to Therapy; Prefrontal Cortex; Publishing; Randomized; Research Domain Criteria; Resistance; Rest; Scanning; Selection for Treatments; Site; Symptoms; System; Testing; Time; Transcranial magnetic stimulation; Work; anxious; arm; biomarker discovery; biotypes; clinical predictors; comparative efficacy; confirmatory trial; depressive symptoms; disability; disorder subtype; efficacy evaluation; electric field; emotion regulation; improved; indexing; individual patient; machine learning method; novel; pharmacologic; predicting response; predictive marker; repetitive transcranial magnetic stimulation; response; standard of care; tractography; treatment response; treatment-resistant depression

Major depressive disorder (MDD) is a leading cause of global disability, and approximately 30% of MDD patients are resistant to conventional antidepressant pharmacotherapy. Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an FDA-cleared intervention with proven efficacy in treatment-resistant depression, but only 30–40% of these patients achieve remission after a single course. Other studies have shown that rTMS targeting the dorsomedial PFC (DMPFC) is comparably effective, but biomarkers for informing target site selection and predicting differential treatment response are not currently available. Diagnostic heterogeneity has been a major obstacle to biomarker discovery efforts. Recently, we developed and validated an approach to diagnosing four novel MDD subtypes or “biotypes” defined by distinct resting state functional connectivity (RSFC) patterns in Valence System circuits and predicting differing antidepressant responses at the individual level to rTMS targeting the DMPFC. This confirmatory efficacy trial will test a novel, biotype-guided treatment selection strategy motivated by the hypothesis that an individual patient's likelihood of responding to left DLFPC vs. DMPFC rTMS is determined in part by individual differences in 1) the degree to which their symptoms are driven by dysfunction in specific downstream amygdala, striatal, and salience network targets comprising aspects of Valence Systems; and 2) the degree to which dysfunction in those targets can be modulated by stimulating the left DLPFC or DMPFC. Subjects (N=405) will be randomized to receive a) biotype-guided 10 Hz rTMS targeting the DMPFC or left DLPFC; b) to a disconfirmation arm receiving rTMS targeting the opposite site; and c) to a third arm receiving FDA-cleared, standard-of-care 10 HZ rTMS targeting the left DLFPC, regardless of biotype. All patients will be tested before and after treatment on a battery of fMRI, behavioral, and clinical assessments, grounded in RDoC-informed measures of emotion regulation and effort valuation, which will enable us to validate downstream brain circuit treatment targets and test for target engagement, in conjunction with state-of-the-art, anatomically realistic electric field modeling and fiber tractography. The primary goal is to confirm the efficacy of a novel RSFC biomarker-guided approach to differential treatment selection in treatment resistant depression, with the potential for significantly enhanced efficacy compared to the current standard-of-care.

重度抑郁症（MDD）是全球残疾的主要原因，约占MDD的30％ 患者对常规抗抑郁药疗法具有抗性。重复的经颅磁 左下角前额叶皮层（DLPFC）的刺激（RTMS）是FDA清除干预措施 抗治疗抑郁症的效率，但只有30-40％ 课程。其他研究表明，针对背部PFC（DMPFC）的RTMS相当有效， 但是用于告知目标现场选择和预测差异治疗反应的生物标志物不是 目前可用。诊断异质性一直是生物标志物发现工作的主要障碍。 最近，我们开发了一种诊断四种新型MDD亚型或“生物型”的方法 由价值系统电路中的不同静止状态功能连接（RSFC）模式定义 在单个级别对靶向DMPFC的RTMS上预测不同的抗抑郁反应。这 确认性效率试验将测试一种新型生物型引导的治疗选择策略 假设个体患者对左DLFPC响应DLFPC与DMPFC RTMS的可能性是在 一部分是由单个差异的部分。 下游杏仁核，纹状体和显着性网络目标完成了价系统的各个方面；和2） 可以通过刺激左DLPFC或DMPFC来调节这些目标中功能障碍的程度。 受试者（n = 405）将被随机接收a）针对DMPFC或左的生物型引导的10 Hz RTM DLPFC; b）接收针对相对位置的RTM的脱节臂； c）接收第三臂 FDA清除，标准的10 Hz RTM，靶向左DLFPC，无论生物型如何。所有患者将是 通过fMRI，行为和临床评估进行治疗前后测试， 情绪调节和努力价值的RDOC信息衡量标准，这将使我们能够验证 下游脑电路治疗目标和测试目标参与以及最先进的 解剖学上逼真的电场建模和纤维拖拉机。主要目标是确认效率 一种新型的RSFC生物标志物引导的方法，用于抗治疗中的差异治疗选择 抑郁症，与当前的护理标准相比，效率显着提高。