Yale-NUS College, Singapore 637551, Singapore.
Institute of Molecular and Cell Biology (IMCB), Singapore 637551, Singapore.
Int J Mol Sci. 2020 Sep 7;21(18):6525. doi: 10.3390/ijms21186525.
Depression impacts the lives and daily activities of millions globally. Research into the neurobiology of lateral habenula circuitry and the use of psychedelics for treating depressive states has emerged in the last decade as new directions to devise interventional strategies and therapies. Several clinical trials using deep brain stimulation of the habenula, or using ketamine, and psychedelics that target the serotonergic system such as psilocybin are also underway. The promising early results in these fields require cautious optimism as further evidence from experiments conducted in animal systems in ecologically relevant settings, and a larger number of human studies with improved spatiotemporal neuroimaging, accumulates. Designing optimal methods of intervention will also be aided by an improvement in our understanding of the common genetic and molecular factors underlying disorders comorbid with depression, as well as the characterization of psychedelic-induced changes at a molecular level. Advances in the use of cerebral organoids offers a new approach for rapid progress towards these goals. Here, we review developments in these fast-moving areas of research and discuss potential future directions.
抑郁症影响着全球数百万人的生活和日常活动。过去十年， lateral habenula 电路的神经生物学研究和使用迷幻剂治疗抑郁状态已成为设计干预策略和治疗方法的新方向。目前也有几项临床试验使用了 habenula 的深部脑刺激，或使用氯胺酮和作用于血清素能系统的迷幻剂，如裸盖菇素。这些领域的早期结果令人鼓舞，需要保持谨慎的乐观态度，因为在生态相关环境中进行的动物系统实验以及更多的具有改进时空神经影像学的人类研究积累了更多证据。随着对与抑郁共病相关的常见遗传和分子因素的理解的提高，以及对迷幻剂诱导的分子水平变化的特征描述的提高，设计最佳的干预方法也将得到帮助。大脑类器官的使用进展为实现这些目标提供了一种新方法。在这里，我们回顾了这些快速发展的研究领域的最新进展，并讨论了潜在的未来方向。
