Behavioral ERP and EEG Asymmetry in Affective Disorders

描述（由申请人提供）：研究发现抑郁症患者存在双耳分听、电生理（EEG/ERP）和神经认知异常的证据，这些证据与抗抑郁药的临床反应有关。半球的不对称性，定量脑电图在α/θ波段和强度依赖性的听觉事件相关电位（ERP）的措施显示特别的承诺是预测的响应选择性5-羟色胺再摄取抑制剂（SSRI）。然而，大多数研究的样本量都很小，对SSRI抗抑郁药预测因子的特异性知之甚少。即将进行的双重治疗临床试验提供了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艾司西酞普兰（ESC）治疗反应预测因子的价值，而不是去甲肾上腺素/多巴胺再摄取抑制剂（NDRI）安非他酮（BUP）。患者被随机分配到12周的治疗与ESC，BUP或这些抗抑郁药的组合（ESC + BUP）。将在基线时对未用药的抑郁患者和健康对照进行一系列测试，包括静息EEG、听觉ERP的强度依赖性、新奇古怪任务、双耳分听和神经认知测试。在治疗1周后和12周后再次对患者进行EEG和听觉ERP测量，并以相同的间隔对对照进行重新测试。这将使我们能够检查这些电生理测量是否在治疗过程中发生变化，或者是稳定的、不依赖于状态的标记。一项临床前研究发现，在ESC + BUP联合给药后，中缝背核中5-羟色胺神经元的放电率显著增加，但单独使用任一种药物后均未增加，这可能是这种双重治疗更快速和获益增加的原因。如果这转化为人类，ESC + BUP将被预测对EEG和听觉ERP测量具有急性和慢性影响，这在单独使用抗抑郁药时未见。此外，我们还将研究脑电图和听觉ERP的急性变化是否能预测哪些患者在联合治疗后症状会缓解。本项目的长期目标是促进电生理和行为测试的发展，这些测试可以帮助临床医生选择最有利于抑郁症患者的抗抑郁药。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治疗反应预测因子的价值进行前瞻性研究。这项研究可以转化为临床辅助工具的发展，为个别抑郁症患者选择治疗方法。

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.