Benedetti Francesco, Smeraldi Enrico
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milano, Italy.
Curr Pharm Des. 2009;15(22):2637-49. doi: 10.2174/138161209788957447.
Despite confirmed evidences about some neurochemical effects of antidepressant treatments, there is still a high level of uncertainty about which biological changes are needed to recover from a major depressive episode. Changes of monoaminergic neurotransmission are paralleled by profound changes in brain metabolism, neural responses to stimuli, sleep architecture, biological rhythms, and, at the intracellular level, neuronal signaling pathways regulating gene expression, neuroplasticity, and neurotrophic mechanisms. Sleep deprivation targets the biological mechanisms which are responsible for the possibility, unique to mood disorders, of rapid switching between depression, euthymia, and mania. The rapidity of action of sleep deprivation enables the study of the correlates of antidepressant response at close time points, providing a good model to study the biological basis of the antidepressant response and of the pathophysiology of affective illness. Current knowledge suggests that multiple neurobiological effects of sleep deprivation are responsible for the clinical mood amelioration, suggesting a multi-target mechanism of action. An impressive group of brain imaging studies using different brain imaging techniques (positron emission tomography, single photon emission tomography, functional magnetic resonance imaging, proton spectroscopy, arterial spin labeling) showed that clinical response is associated with changes in the functioning of specific brain areas. The combination of these new methodological acquisitions with the classical neurobiological and pharmacogenetic perspective provides an evolving knowledge about brain changes associated with antidepressant response, and will then help to identify the real targets of antidepressant treatment.
尽管有确凿证据表明抗抑郁治疗具有某些神经化学效应，但对于从重度抑郁发作中恢复需要哪些生物学变化，仍存在高度不确定性。单胺能神经传递的变化伴随着脑代谢、对刺激的神经反应、睡眠结构、生物节律以及细胞内水平上调节基因表达、神经可塑性和神经营养机制的神经元信号通路的深刻变化。睡眠剥夺针对的是那些导致情绪障碍特有的在抑郁、心境正常和躁狂之间快速转换可能性的生物学机制。睡眠剥夺起效迅速，能够在相近时间点研究抗抑郁反应的相关因素，为研究抗抑郁反应的生物学基础和情感性疾病的病理生理学提供了一个良好模型。目前的知识表明，睡眠剥夺的多种神经生物学效应导致了临床情绪改善，提示其作用机制为多靶点机制。一组令人印象深刻的脑成像研究使用了不同的脑成像技术（正电子发射断层扫描、单光子发射断层扫描、功能磁共振成像、质子磁共振波谱、动脉自旋标记），结果显示临床反应与特定脑区功能的变化有关。这些新方法与经典神经生物学和药物遗传学观点相结合，为与抗抑郁反应相关的脑变化提供了不断发展的知识，进而有助于确定抗抑郁治疗的真正靶点。
