Salt Lake City Veterans Affairs Medical Center and Department of Psychiatry, Salt Lake City, Utah, USA.
Biol Psychiatry. 2013 Jun 15;73(12):1213-21. doi: 10.1016/j.biopsych.2013.02.008. Epub 2013 Mar 27.
Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals with treatment-resistant depression. The neural mechanisms underlying this effect remain unknown.
In this preliminary study, 20 unmedicated participants with treatment-resistant MDD underwent positron emission tomography to measure regional cerebral glucose metabolism at baseline and following ketamine infusion (single dose of .5mg/kg intravenous over 40minutes). Metabolic data were compared between conditions using a combination of region-of-interest and voxelwise analyses, and differences were correlated with the associated antidepressant response.
Whole-brain metabolism did not change significantly following ketamine. Regional metabolism decreased significantly under ketamine in the habenula, insula, and ventrolateral and dorsolateral prefrontal cortices of the right hemisphere. Metabolism increased postketamine in bilateral occipital, right sensorimotor, left parahippocampal, and left inferior parietal cortices. Improvement in depression ratings correlated directly with change in metabolism in right superior and middle temporal gyri. Conversely, clinical improvement correlated inversely with metabolic changes in right parahippocampal gyrus and temporoparietal cortex.
Although preliminary, these results indicate that treatment-resistant MDD subjects showed decreased metabolism in the right habenula and the extended medial and orbital prefrontal networks in association with rapid antidepressant response to ketamine. Conversely, metabolism increased in sensory association cortices, conceivably related to the illusory phenomena sometimes experienced with ketamine. Further studies are needed to elucidate how these functional anatomical changes relate to the molecular mechanisms underlying ketamine's rapid antidepressant effects.
多项证据表明，谷氨酸能系统在重度抑郁症（MDD）的病理生理学中起作用。氯胺酮是一种 N-甲基-D-天冬氨酸拮抗剂，可迅速改善治疗抵抗性抑郁症患者的抑郁症状。其作用的神经机制尚不清楚。
在这项初步研究中，20 名未经治疗的治疗抵抗性 MDD 患者接受正电子发射断层扫描，以在基线和氯胺酮输注后（静脉内 0.5mg/kg 单次剂量，40 分钟内输注完毕）测量区域性脑葡萄糖代谢。使用感兴趣区域和体素分析的组合比较两种条件下的代谢数据，并将差异与相关的抗抑郁反应相关联。
氯胺酮治疗后全脑代谢没有明显变化。在右侧大脑的缰核、岛叶、腹外侧和背外侧前额叶皮质下，氯胺酮治疗下的局部代谢显著降低。氯胺酮治疗后双侧枕叶、右侧感觉运动、左侧海马旁回和左侧顶下小叶的代谢增加。抑郁评分的改善与右侧颞上和中回代谢变化直接相关。相反，临床改善与右侧海马旁回和颞顶叶皮质的代谢变化呈负相关。
尽管初步研究结果表明，治疗抵抗性 MDD 患者的右侧缰核和扩展的内侧和眶额前皮质网络的代谢降低与氯胺酮快速抗抑郁反应有关。相反，感觉联想皮质的代谢增加，这可能与氯胺酮有时引起的幻觉现象有关。需要进一步的研究来阐明这些功能解剖学变化与氯胺酮快速抗抑郁作用的分子机制之间的关系。
