Mark J Niciu, Daniel C Mathews, Dawn F Ionescu, Erica M Richards, Maura L Furey, Peixiong Yuan, Allison C Nugent, Ioline D Henter, Rodrigo Machado-Vieira, Carlos A Zarate
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引用次数: 10
Abstract
Background: Recently, surrogate neurobiological biomarkers that correlate with target engagement and therapeutic response have been developed and tested in early phase studies of mood disorders.
Objective: The identification of biomarkers could help develop personalized psychiatric treatments that may impact public health.
Methods: These biomarkers, which are associated with clinical response post-treatment, can be directly validated using multimodal approaches including genetic tools, proteomics/metabolomics, peripheral measures, neuroimaging, biostatistical predictors, and clinical predictors.
Results: To date, early phase biomarker studies have sought to identify measures that can serve as "biosignatures", or biological patterns of clinical response. These studies have also sought to identify clinical predictors and surrogate outcomes associated with pathophysiological domains consistently described in the National Institute of Mental Health's (NIMH) new Research Domain Criteria (RDoC). Using the N-methyl-D-aspartate (NMDA) antagonist ketamine as an example, we identified changes in several domains (clinical, cognitive, and neurophysiological) that predicted ketamine's rapid and sustained antidepressant effects in individuals with treatment-resistant major depressive disorder (MDD) or bipolar depression.
Discussion: These approaches may ultimately provide clues into the neurobiology of psychiatric disorders and may have enormous impact Backon the development of novel therapeutics.
背景:最近,与靶标参与和治疗反应相关的替代神经生物学生物标志物已经被开发出来,并在情绪障碍的早期研究中进行了测试。目的:鉴定生物标志物有助于开发个性化的精神病学治疗,可能影响公众健康。方法:这些与治疗后临床反应相关的生物标志物可以使用多种方法直接验证,包括遗传工具、蛋白质组学/代谢组学、外周测量、神经影像学、生物统计学预测因子和临床预测因子。结果:迄今为止,早期阶段的生物标志物研究已经试图确定可以作为“生物特征”的措施,或临床反应的生物学模式。这些研究还试图确定与国家精神卫生研究所(NIMH)新研究领域标准(RDoC)一致描述的病理生理领域相关的临床预测因素和替代结果。以n -甲基- d -天冬氨酸(NMDA)拮抗剂氯胺酮为例,我们确定了几个领域(临床、认知和神经生理)的变化,这些变化预测了氯胺酮对难治疗的重度抑郁症(MDD)或双相抑郁症患者的快速和持续的抗抑郁作用。讨论:这些方法可能最终为精神疾病的神经生物学提供线索,并可能对新疗法的发展产生巨大影响。
期刊介绍:
The mission of the Archives of Clinical Psychiatry is to provide relevant clinical information and clinically oriented research, including also basic research, whose results have potential implications for clinical practice. The scope of the journal encompasses: Human Sciences, Basic and Clinical Neuroscience, and Clinical Psychiatry. The Archives of Clinical Psychiatry strives to inform and to educate mental health care professionals and to stimulate debates and further exploration into the nature, causes, treatment, and public health importance of mental health issues.