Time-Frequency Measures for Predicting Response to Antidepressants

描述(由申请人提供)：NIMH的战略目标解决了对个性化药物的需求，即为给定的个人选择最佳治疗。电生理学研究的结果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测量和听觉诱发电位的常规测量(N1，P2)。这个R03应用程序建议对RO1项目(MH36295；G.Bruder，PI)的独特数据集进行广泛的时频(TF)分析，这将产生关于潜在的时间和频率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，该研究检验了电生理学和神经认知测量对预测SSRI抗抑郁剂(艾司匹兰)、NDRI抗抑郁剂(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，奇怪任务中的事件相关电位(ERPs)，以及听觉诱发电位(LDAEP)的响度依赖性，显示出能够区分对SSRI反应良好的患者和不对SSRI反应良好的患者。这些措施在治疗前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。建议的分析将使用一种新的方法来从无参考电流源密度测量中获得Tf分量。我们将检查事件相关振荡，并确定治疗应答者和对新刺激无反应者之间的听觉ERP差异是否源于中线theta活动的事件相关同步或相位锁定，这被认为涉及前扣带皮质的定向过程。除了检查theta活动外，我们还将在LDAEP范式中测试应答者和无应答者在事件相关伽马上的预测差异。最后，我们将确定在接受SSRI、NDRI或两种抗抑郁药物联合治疗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。在一项临床前研究中，联合使用SSRI和NDRI抗抑郁药在增加5-羟色胺活性方面具有协同作用，结果导致预测，双重治疗将比单独使用任何一种抗抑郁药在神经生理和认知功能方面的改善更大。 公共卫生相关性：拟议中的研究将提供新的分析，以扩展和澄清我们对SSRI和NDRI抗抑郁药物的应答者和无应答者的时间和频率锁定神经振荡的知识，并可能进一步加强这些电生理指标的预测价值。这可以转化为开发临床助手，根据简单且经济高效的脑电记录为个别抑郁症患者选择治疗方案。如果同时使用SSRI和NDRI抗抑郁药比单独使用任何一种抗抑郁药对神经生理功能的改善都更大，这也将具有临床重要性。

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.