Time-Frequency Measures for Predicting Response to Antidepressants

描述（由申请人提供）：NIMH战略目标解决个性化医疗的需求，即为特定个体选择最佳治疗。电生理学研究的发现为确定抗抑郁药物临床反应的预测因素带来了希望。然而，这些研究仅限于标准频段的脑电图测量和听觉诱发电位的常规测量（N1, P2）。该RO3应用程序建议对来自RO1项目（MH36295； G. Bruder， PI）的独特数据集进行广泛的时频（TF）分析，这将产生关于潜在时频锁定神经振荡的新发现，并可能加强这些电生理测量的预测价值。这些数据是在一项研究中获得的，该研究检查了电生理和神经认知测量对预测SSRI抗抑郁药（艾司西酞普兰）、NDRI抗抑郁药（安非他酮）或这些治疗组合的临床反应的价值。电生理测量，包括静息脑电图、新奇古怪任务期间的事件相关电位（ERPs）和听觉诱发电位（LDAEPs）的响度依赖性，显示出能够区分对SSRI有良好反应和没有反应的患者的希望。这些措施在预处理阶段和治疗期间再次实施，以检查这些抗抑郁药的急性和慢性影响。提出的分析将使用一种新的方法，从无参考电流源密度测量中推导出TF分量。我们将研究与事件相关的振荡，并确定对新刺激有反应者和无反应者之间的听觉ERP差异是否来自与事件相关的同步或中线θ波活动的锁相，这被认为涉及前扣带皮层的定向过程。除了检查θ波活动外，我们还将在LDAEP范式中测试反应者和无反应者在事件相关γ波中的预测差异。最后，我们将确定在接受SSRI、NDRI或两种抗抑郁药物双重治疗12周后，这些TF指标是否有变化，并检查这些变化与抑郁和认知功能改善的关系。一项临床前研究结果显示，SSRI和NDRI抗抑郁药联合使用在增加血清素活性方面具有协同作用，因此预测双重治疗比单独使用任何一种抗抑郁药更能改善神经生理和认知功能。

DESCRIPTION (provided by applicant): An NIMH Strategic Objective addresses the need for personalized medicine, that is, choosing the best treatment for a given individual. Findings of electrophysiologic studies have raised hopes for identifying predictors of clinical response to antidepressants. These studies have, however, been limited to EEG measures in standard frequency bands and conventional measures of auditory evoked potentials (N1, P2). This RO3 application proposes to do extensive time-frequency (TF) analyses of a unique data set from an RO1 project (MH36295; G. Bruder, PI), which will generate new findings concerning underlying time- and frequency-locked neural oscillations and may strengthen the predictive value of these electrophysiologic measures. The data were obtained in a study examining the value of electrophysiologic and neurocognitive measures for predicting clinical response to an SSRI antidepressant (escitalopram), an NDRI antidepressant (bupropion), or a combination of these treatments. The electrophysiologic measures, including resting EEG, event-related potentials (ERPs) during a novelty oddball task, and loudness dependency of auditory evoked potentials (LDAEPs) show promise of being able to differentiate patients who respond favorably to an SSRI and those who do not. These measures were administered in a pretreatment session and again during treatment to examine acute and chronic effects of these antidepressants. The proposed analyses will use a new approach to derive TF components from reference-free current source density measures. We will examine event-related oscillations and determine whether auditory ERP differences between treatment responders and nonresponders to novel stimuli result from event-related synchronization or phase-locking of midline theta activity, which is thought to involve orienting processes in anterior cingulate cortex. In addition to examining theta activity, we will test for predicted differences between responders and nonresponders in event-related gamma in the LDAEP paradigm. Lastly, we will determine whether there are changes in these TF measures following 12 weeks of treatment with an SSRI, NDRI or dual therapy with both antidepressants and examine the relation of these changes to improvement of depression and cognitive function. Results from a preclinical study, in which combined administration of SSRI and NDRI antidepressants had synergistic effects in increasing serotonin activity, led to the prediction that dual therapy will result in greater improvements in neurophysiologic and cognitive function than either antidepressant alone. PUBLIC HEALTH RELEVANCE: The proposed study will provide new analyses to extend and clarify our knowledge of time- and frequency-locked neural oscillations in responders and nonresponders to SSRI and NDRI antidepressants and may further strengthen the predictive value of these electrophysiologic measures. This could translate into development of clinical aides for selecting treatments for individual depressed patients based on simple and cost-effective EEG recordings. It would also be of clinical importance if it were shown that combined treatment with both SSRI and NDRI antidepressants results in greater improvement in neurophysiologic function than either antidepressant alone.