Depression Task Force, Hope for Depression Research Foundation, New York, NY 10019, United States; University of Michigan, United States.
Depression Task Force, Hope for Depression Research Foundation, New York, NY 10019, United States; Columbia University, United States; New York State Psychiatric Institute, United States.
Neurosci Biobehav Rev. 2018 Jan;84:272-288. doi: 10.1016/j.neubiorev.2017.08.019. Epub 2017 Aug 30.
An estimated 50% of depressed patients are inadequately treated by available interventions. Even with an eventual recovery, many patients require a trial and error approach, as there are no reliable guidelines to match patients to optimal treatments and many patients develop treatment resistance over time. This situation derives from the heterogeneity of depression and the lack of biomarkers for stratification by distinct depression subtypes. There is thus a dire need for novel therapies. To address these known challenges, we propose a multi-scale framework for fundamental research on depression, aimed at identifying the brain circuits that are dysfunctional in several animal models of depression as well the changes in gene expression that are associated with these models. When combined with human genetic and imaging studies, our preclinical studies are starting to identify candidate circuits and molecules that are altered both in models of disease and in patient populations. Targeting these circuits and mechanisms can lead to novel generations of antidepressants tailored to specific patient populations with distinctive types of molecular and circuit dysfunction.
据估计，有 50%的抑郁症患者接受现有干预措施的治疗效果并不理想。即使最终康复，许多患者也需要反复尝试，因为没有可靠的指南来将患者与最佳治疗方法相匹配，而且许多患者随着时间的推移会产生治疗抵抗。这种情况源于抑郁症的异质性和缺乏用于区分不同抑郁症亚型的生物标志物。因此，非常需要新的治疗方法。为了解决这些已知的挑战，我们提出了一个针对抑郁症的基础研究的多尺度框架，旨在确定几种抑郁症动物模型中功能失调的大脑回路，以及与这些模型相关的基因表达变化。当与人类遗传和影像学研究相结合时，我们的临床前研究开始确定候选回路和分子，这些回路和分子在疾病模型和患者群体中都发生了改变。针对这些回路和机制可以为具有不同分子和回路功能障碍类型的特定患者群体带来量身定制的新一代抗抑郁药。
