Psychiatry Research Unit, University of Fribourg, Fribourg Network of Mental Health, Chemin du Cardinal-Journet 3, 1752 Villars-sur-Glâne, Switzerland; Department of Neuroscience, Institute of Psychiatry, Catholic University Medical School, Largo Francesco Vito 1, 00168 Rome, Italy.
Psychiatry Research Unit, University of Fribourg, Fribourg Network of Mental Health, Chemin du Cardinal-Journet 3, 1752 Villars-sur-Glâne, Switzerland.
Neurosci Biobehav Rev. 2022 Nov;142:104906. doi: 10.1016/j.neubiorev.2022.104906. Epub 2022 Oct 4.
The monoamine hypothesis has dominated research on the pathophysiology of mood disorders as well as the development of therapeutic drugs by over half a century. Nowadays a change of perspective is taking place. The glutamate system is increasingly implicated in the pathophysiology of mood disorders. The evidence spans from animal, post-mortem, imaging, pharmacological and genome-wide association studies. Bipolar disorder has been recently re-conceptualized as a synaptic plasticity-related disorder rather than simply as a result of deficits or excesses in individual neurotransmitters. A paradigm shift from a monoamine hypothesis to a neuroplasticity hypothesis focused on glutamate may represent a substantial advancement in the research for new drugs and therapies. In this review we summarize data from clinical and pre-clinical studies that have addressed glutamatergic alterations in bipolar disorder. Along with an in-depth discussion of glutamatergic alterations in bipolar disorder, we also report available data on the neuroprotective and neuroplastic potential of the classic mood stabilizers, ketamine, and psychedelics. The glutamatergic mechanisms underlying the efficacy of these drugs are described and discussed.
单胺假说主导了对心境障碍的病理生理学以及治疗药物的开发研究已有半个多世纪。如今，这种观点正在发生变化。谷氨酸系统越来越多地与心境障碍的病理生理学有关。从动物、尸检、成像、药理学和全基因组关联研究都有证据支持。双相情感障碍最近被重新概念化为与突触可塑性相关的疾病，而不仅仅是由于单个神经递质的缺乏或过多导致的。从单胺假说到专注于谷氨酸的神经可塑性假说的范式转变，可能是新药物和治疗方法研究的重大进展。在这篇综述中，我们总结了来自临床和临床前研究的数据，这些研究探讨了双相情感障碍中的谷氨酸能改变。除了深入讨论双相情感障碍中的谷氨酸能改变外，我们还报告了经典心境稳定剂、氯胺酮和迷幻药的神经保护和神经可塑性潜力的现有数据。描述并讨论了这些药物疗效的谷氨酸能机制。
