Identifying response and predictive biomarkers for Transcranial magnetic stimulation outcomes: protocol and rationale for a mechanistic study of functional neuroimaging and behavioral biomarkers in veterans with Pharmacoresistant depression.
Identifying response and predictive biomarkers for Transcranial magnetic stimulation outcomes: protocol and rationale for a mechanistic study of functional neuroimaging and behavioral biomarkers in veterans with Pharmacoresistant depression.
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识别经颅磁刺激结果的反应和预测生物标志物：对患有抗药性抑郁症的退伍军人进行功能性神经成像和行为生物标志物机制研究的方案和原理。
DOI：
10.1186/s12888-020-03030-z
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发表时间：
2021-01-13
期刊：
影响因子：
4.4
通讯作者：
Holtzheimer PE
中科院分区：
文献类型：
--
作者：
Williams LM;Coman JT;Stetz PC;Walker NC;Kozel FA;George MS;Yoon J;Hack LM;Madore MR;Lim KO;Philip NS;Holtzheimer PE
尽管重复经颅磁刺激（“TMS”）正在成为治疗耐药性抑郁症的金标准，但我们缺乏神经靶标生物标志物来识别谁最有可能对 TMS 做出反应以及原因。为了解决这一知识差距，我们评估了由背外侧前额叶皮层锚定的认知控制回路的激活和功能连接、默认模式网络和注意回路的区域以及与膝下前扣带回的相互作用定义的神经目标。我们评估这些目标及其之间的相互作用是否以剂量依赖性方式发生变化，这些神经目标的变化是否对应于认知行为表现的变化，以及神经目标和认知行为表现的基线和早期变化是否可以预测随后的症状严重程度、自杀性和生活质量结果。这项研究是与退伍军人健康管理局国家临床 TMS 计划合作进行的一项务实、机械性试验。目标招募对象包括 100 名患有耐药性重度抑郁症 (MDD) 的退伍军人。所有退伍军人都将接受 TMS 临床课程，并将在 TMS 开始前的“基线”、TMS 开始后的“第一周”（目标为 5 个疗程）和 TMS 完成时的“治疗后”（目标为 30 个疗程）进行评估。退伍军人将使用功能磁共振成像（fMRI）、认知行为表现电池和制定的问卷进行评估。多元线性混合模型将用于评估神经靶标是否随 TMS 作为剂量的函数而变化（目标 1），神经靶标的范围和变化是否与行为表现的程度相关并预测行为表现的程度（目标 3），以及神经靶标变化的程度是否预测症状严重程度、自杀性和生活质量的改善（目标 3）。对于这三个目标，我们还将评估生物性别和年龄等基线调节因素的贡献。据我们所知，我们的研究将是第一个实用的、机制性的观察试验，使用功能磁共振成像和认知行为表现作为耐药性 MDD 的 TMS 治疗反应的生物标志物。该试验的结果将使提供者能够选择合适的 TMS 治疗候选者，并通过评估基线和早期治疗期间的回路连接和认知行为表现来更好地预测治疗反应。 ClinicalTrials.gov NCT04663481，2020 年 12 月 5 日，回顾注册。第一位退伍军人于 2020 年 10 月 30 日入伍。
Although repetitive transcranial magnetic stimulation (‘TMS’) is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge we evaluate neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate. We evaluate whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes. This study is designed as a pragmatic, mechanistic trial partnering with the National Clinical TMS Program of the Veteran’s Health Administration. Target enrollment consists of 100 veterans with pharmacoresistant Major Depressive Disorder (MDD). All veterans will receive a clinical course of TMS and will be assessed at ‘baseline’ pre-TMS commencement, ‘first week’ after initiation of TMS (targeting five sessions) and ‘post-treatment’ at the completion of TMS (targeting 30 sessions). Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires. Multivariate linear mixed models will be used to assess whether neural targets change with TMS as a function of dose (Aim 1), whether extent and change of neural target relates to and predicts extent of behavioral performance (Aim 3), and whether extent of neural target change predicts improvement in symptom severity, suicidality, and quality of life (Aim 3). For all three aims, we will also assess the contribution of baseline moderators such as biological sex and age. To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD. The results of this trial will allow providers to select suitable candidates for TMS treatment and better predict treatment response by assessing circuit connectivity and cognitive-behavioral performance at baseline and during early treatment. ClinicalTrials.gov NCT04663481, December 5th, 2020, retrospectively registered. The first veteran was enrolled October 30th, 2020.
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影响因子：
5.7
作者：
Fox MD;Liu H;Pascual-Leone A
通讯作者：
Pascual-Leone A
影响因子：
5.7
作者：
Dosenbach NUF;Koller JM;Earl EA;Miranda-Dominguez O;Klein RL;Van AN;Snyder AZ;Nagel BJ;Nigg JT;Nguyen AL;Wesevich V;Greene DJ;Fair DA
通讯作者：
Fair DA
DOI：
10.1001/jama.2017.3826
发表时间：
2017-04-18
期刊：
JAMA
影响因子：
--
作者：
Friedrich, M J
通讯作者：
Friedrich, M J
影响因子：
2.6
作者：
Bilder, Robert M.;Postal, Karen S.;Woodhouse, Jonathan
通讯作者：
Woodhouse, Jonathan
DOI：
10.1177/1073858414525995
发表时间：
2014-12
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Cole MW;Repovš G;Anticevic A
通讯作者：
Anticevic A