Time-Frequency Measures for Predicting Response to Antidepressants

描述（由申请人提供）：NIMH战略目标解决了个性化医疗的需求，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临床反应的预测因子带来了希望。然而，这些研究仅限于标准频段的EEG测量和听觉诱发电位（N1，P2）的常规测量。该RO 3应用程序建议对来自RO 1项目（MH 36295; G.布鲁德，PI），这将产生新的发现，有关潜在的时间和频率锁定的神经振荡，并可能加强这些电生理措施的预测价值。这些数据是在一项研究中获得的，该研究检查了电生理学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。电生理措施，包括静息脑电图，事件相关电位（ERP）在一个新奇的古怪的任务，和响度依赖性的听觉诱发电位（LDAEPs）显示的承诺，能够区分患者谁积极响应SSRI和那些谁不。这些措施在治疗前和治疗期间进行，以检查这些抗抑郁药的急性和慢性影响。拟议的分析将使用一种新的方法来获得TF组件的参考电流源密度的措施。我们将研究事件相关的振荡，并确定是否治疗反应者和无反应者之间的听觉ERP差异，以新颖的刺激导致事件相关的同步或相位锁定的中线θ活动，这被认为是涉及前扣带皮层的定向过程。除了检查theta活动，我们将测试LDAEP范式中事件相关γ的应答者和无应答者之间的预测差异。最后，我们将确定在使用SSRI、NDRI或两种抗抑郁药的双重治疗12周后，这些TF指标是否发生变化，并检查这些变化与抑郁症和认知功能改善的关系。一项临床前研究的结果表明，SSRI和NDRI抗抑郁药联合给药在增加5-羟色胺活性方面具有协同作用，预测双重治疗将比单独使用任一种抗抑郁药更能改善神经生理和认知功能。 公共卫生相关性：拟议的研究将提供新的分析，以扩展和澄清我们对SSRI和NDRI抗抑郁药应答者和非应答者的时间和频率锁定神经振荡的认识，并可能进一步加强这些电生理指标的预测价值。这可以转化为基于简单且具有成本效益的EEG记录为个体抑郁症患者选择治疗方法的临床辅助工具的开发。如果SSRI和NDRI抗抑郁药的联合治疗比单独使用任何一种抗抑郁药能更好地改善神经生理功能，这也具有临床意义。

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.