Behavioral ERP and EEG Asymmetry in Affective Disorders

描述(申请人提供)：研究已经发现抑郁症患者存在两分听、电生理(EEG/ERP)和神经认知异常的证据，这与抗抑郁药物的临床反应有关。测量大脑半球的不对称性、α/theta频段的定量脑电和听觉事件相关电位(ERPs)的强度依赖性显示出特别有希望预测选择性5-羟色胺再摄取抑制剂(SSRI)的反应。然而，在大多数研究中，样本量很小，对SSRI抗抑郁药预测因素的特异性知之甚少。即将进行的双重疗法临床试验提供了一个进行前瞻性研究的理想机会，以评估这些电生理和认知指标作为SSRI爱司匹兰(ESC)与去甲肾上腺素/多巴胺再摄取抑制剂(NDRI)安非他酮(BUP)治疗反应的预测指标的价值。患者被随机分配到ESC、BUP或这些抗抑郁药的组合(ESC+BUP)治疗12周。未经药物治疗的抑郁症患者和健康对照组将在一系列测试中进行基线测试，包括静息脑电、听觉事件相关电位的强度依赖、新奇古怪任务、双耳听力和神经认知测试。患者在治疗1周后再次进行脑电和听觉事件相关电位测试，并在12周后再次进行测试，对照组在相同的时间间隔进行再次测试。这将使我们能够检查这些电生理指标是否在治疗过程中发生变化，或者是稳定的、状态独立的标记物。一项临床前研究发现，联合应用ESC和BUP后，中缝背核5-羟色胺神经元的放电频率显著增加，但单独使用任何一种药物后均不明显，这可能是这种双重治疗更快、更有效的原因。如果这适用于人类，ESC+BUP将被预测对EEG和听觉ERP测量有急性和慢性影响，这两种药物单独使用时都看不到。此外，我们还将研究脑电和听觉事件相关电位的急性变化是否可以预测哪些患者在综合治疗后症状会有所缓解。该项目的长期目标是促进电生理和行为测试的发展，帮助临床医生选择最有利于抑郁症患者的抗抑郁药物。公共卫生相关性：一项比较SSRI、安非他酮或联合治疗的临床试验提供了一个理想的机会，可以对电生理和神经认知测试作为这些抗抑郁药物治疗反应预测指标的价值进行前瞻性研究。这项研究可以转化为为个别抑郁症患者选择治疗方案的临床辅助工具的开发。

DESCRIPTION (provided by applicant): Studies have found evidence of dichotic listening, electrophysiologic (EEG/ERP), and neurocognitive abnormalities in depressed patients, which are related to clinical response to antidepressants. Measures of hemispheric asymmetry, quantitative EEG in alpha/theta bands and intensity-dependence of auditory event-related potentials (ERPs) show particular promise of being predictive of response to a selective serotonin reuptake inhibitor (SSRI). Sample size in most studies has, however, been small and little is known about the specificity of predictors to SSRI antidepressants. An upcoming dual therapy clinical trial offers an ideal opportunity to conduct a prospective study to assess the value of these electrophysiologic and cognitive measures as predictors of therapeutic response to the SSRI escitalopram (ESC) as opposed to the noradrenaline/dopamine reuptake inhibitor (NDRI) bupropion (BUP). Patients are randomly assigned to 12 weeks of treatment with ESC, BUP or a combination of these antidepressants (ESC + BUP). Unmedicated depressed patients and healthy controls will be tested at baseline on a battery of tests, including resting EEG, intensity-dependence of auditory ERPs, novelty oddball task, dichotic listening, and neurocognitive tests. Patients are retested on the EEG and auditory ERP measures after 1 week of treatment and again after 12 weeks, and controls are retested at the same intervals. This will enable us to examine whether these electrophysiologic measures change during treatment or are stable, state-independent markers. A preclinical study found that firing rates of serotonin neurons in the dorsal raphi nucleus were markedly increased after combined administration of ESC + BUP, but not after either drug alone, which could account for the more rapid and increased benefit of this dual treatment. If this translates to humans, ESC + BUP would be predicted to have acute and chronic effects on EEG and auditory ERP measures not seen for either antidepressant alone. Moreover, we will examine whether acute changes in EEG and auditory ERPs predict which patients will show remission of symptoms with combined treatment. The long-range goal of this project is to contribute toward the development of electrophysiologic and behavioral tests that could aid the clinician in choosing antidepressants that will most benefit a depressed patient. PUBLIC HEALTH RELEVANCE: A clinical trial comparing treatment with an SSRI, bupropion or combined therapy offers an ideal opportunity to do a prospective study of the value of electrophysiologic and neurocognitive tests as predictors of therapeutic response to these antidepressants. This research could translate into development of clinical aides for selecting treatments for individual depressed patients.