Department of Psychiatry, Columbia University Medical Center, New York, NY, 10032, USA.
Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, 10954, USA.
Neuropsychopharmacology. 2020 Aug;45(9):1411-1422. doi: 10.1038/s41386-020-0697-9. Epub 2020 May 6.
New treatment development for psychiatric disorders depends critically upon the development of physiological measures that can accurately translate between preclinical animal models and clinical human studies. Such measures can be used both as stratification biomarkers to define pathophysiologically homogeneous patient populations and as target engagement biomarkers to verify similarity of effects across preclinical and clinical intervention. Traditional "time-domain" event-related potentials (ERP) have been used translationally to date but are limited by the significant differences in timing and distribution across rodent, monkey and human studies. By contrast, neuro-oscillatory responses, analyzed within the "time-frequency" domain, are relatively preserved across species permitting more precise translational comparisons. Moreover, neuro-oscillatory responses are increasingly being mapped to local circuit mechanisms and may be useful for investigating effects of both pharmacological and neuromodulatory interventions on excitatory/inhibitory balance. The present paper provides a roadmap for development of neuro-oscillatory responses as translational biomarkers in neuropsychiatric treatment development.
精神障碍的新治疗方法的发展取决于能否开发出可以在临床前动物模型和临床人类研究之间进行准确转换的生理测量方法。这些方法可以用作分层生物标志物,以定义生理上同质的患者群体,也可以用作目标关联生物标志物,以验证临床前和临床干预的效果是否相似。传统的“时域”事件相关电位 (ERP) 迄今为止已被用于转化研究,但受到啮齿动物、猴子和人类研究中时间和分布显著差异的限制。相比之下,在“时频”域内分析的神经振荡反应在跨物种中相对保留,从而可以进行更精确的转化比较。此外,神经振荡反应越来越多地被映射到局部回路机制,并且可能有助于研究药物和神经调节干预对兴奋性/抑制性平衡的影响。本文提供了作为神经精神治疗开发中转译生物标志物的神经振荡反应的发展路线图。