Duman Ronald S, Aghajanian George K, Sanacora Gerard, Krystal John H
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Nat Med. 2016 Mar;22(3):238-49. doi: 10.1038/nm.4050.
Depression is a common, devastating illness. Current pharmacotherapies help many patients, but high rates of a partial response or no response, and the delayed onset of the effects of antidepressant therapies, leave many patients inadequately treated. However, new insights into the neurobiology of stress and human mood disorders have shed light on mechanisms underlying the vulnerability of individuals to depression and have pointed to novel antidepressants. Environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology, resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function. Although current antidepressants, such as serotonin-reuptake inhibitors, produce subtle changes that take effect in weeks or months, it has recently been shown that treatment with new agents results in an improvement in mood ratings within hours of dosing patients who are resistant to typical antidepressants. Within a similar time scale, these new agents have also been shown to reverse the synaptic deficits caused by stress.
抑郁症是一种常见的、具有毁灭性的疾病。目前的药物疗法帮助了许多患者，但部分缓解或无反应的比例很高，而且抗抑郁疗法的效果起效延迟，导致许多患者未得到充分治疗。然而，对压力和人类情绪障碍神经生物学的新见解揭示了个体易患抑郁症的潜在机制，并指向了新型抗抑郁药。环境事件和其他风险因素通过汇聚的分子和细胞机制导致抑郁症，这些机制会破坏神经元功能和形态，从而导致对情绪调节和认知功能至关重要的神经回路功能障碍。尽管目前的抗抑郁药，如血清素再摄取抑制剂，会产生在数周或数月内起效的细微变化，但最近有研究表明，对于对典型抗抑郁药耐药的患者，使用新型药物治疗能在给药数小时内改善情绪评分。在类似的时间范围内，这些新型药物也已被证明能逆转由压力引起的突触缺陷。
