Institute of Pharmacology & Toxicology, University of Zürich, Zürich, Switzerland.
Biol Psychiatry. 2013 Jan 15;73(2):161-8. doi: 10.1016/j.biopsych.2012.07.030. Epub 2012 Sep 7.
Sleep deprivation (wake therapy) provides rapid clinical relief in many patients with major depressive disorder (MDD). Changes in glutamatergic neurotransmission may contribute to the antidepressant response, yet the exact underlying mechanisms are unknown. Metabotropic glutamate receptors of subtype 5 (mGluR5) are importantly involved in modulating glutamatergic neurotransmission and neuronal plasticity. The density of these receptors is reduced in the brain of patients with MDD, particularly in brain structures involved in regulating wakefulness and sleep. We hypothesized that prolonged wakefulness would increase mGluR5 availability in human brain.
Metabotropic glutamate receptor subtype 5 binding was quantified with positron emission tomography in 22 young healthy men who completed two experimental blocks separated by 1 week. Two positron emission tomography examinations were conducted in randomized, crossover fashion with the highly selective radioligand, ¹¹C-ABP688, once after 9 hours (sleep control) and once after 33 hours (sleep deprivation) of controlled wakefulness. ¹¹C-ABP688 uptake was quantified in 13 volumes of interest with high mGluR5 expression and presumed involvement in sleep-wake regulation.
Sleep deprivation induced a global increase in mGluR5 binding when compared with sleep control (p<.006). In anterior cingulate cortex, insula, medial temporal lobe, parahippocampal gyrus, striatum, and amygdala, this increase correlated significantly with the sleep deprivation-induced increase in subjective sleepiness.
This molecular imaging study demonstrates that cerebral functional mGluR5 availability is increased after a single night without sleep. Given that mGluR5 density is reduced in MDD, further research is warranted to examine whether this mechanism is involved in the potent antidepressant effect of wake therapy.
睡眠剥夺（清醒治疗）可使许多重度抑郁症（MDD）患者迅速获得临床缓解。谷氨酸能神经传递的变化可能有助于抗抑郁反应，但确切的潜在机制尚不清楚。代谢型谷氨酸受体 5 型（mGluR5）亚型在调节谷氨酸能神经传递和神经元可塑性方面起着重要作用。这些受体在 MDD 患者的大脑中的密度降低，特别是在参与调节觉醒和睡眠的大脑结构中。我们假设长时间清醒会增加人类大脑中的 mGluR5 可用性。
通过正电子发射断层扫描（PET）在 22 名年轻健康男性中量化代谢型谷氨酸受体亚型 5 的结合，这些男性在 1 周内完成了两个实验块。在随机、交叉设计中，以高度选择性放射性配体¹¹C-ABP688，在 9 小时（睡眠对照）和 33 小时（睡眠剥夺）的清醒控制后，进行了两次 PET 检查。¹¹C-ABP688 摄取量在 13 个具有高 mGluR5 表达和睡眠-觉醒调节参与假定的感兴趣区进行了量化。
与睡眠对照相比，睡眠剥夺诱导了 mGluR5 结合的全局增加（p<.006）。在前扣带回皮质、岛叶、内侧颞叶、海马旁回、纹状体和杏仁核中，这种增加与睡眠剥夺引起的主观嗜睡增加显著相关。
这项分子成像研究表明，在一夜无眠后，大脑功能 mGluR5 的可用性增加。鉴于 MDD 中 mGluR5 的密度降低，需要进一步研究以检查该机制是否参与清醒治疗的强大抗抑郁作用。
