Udina Marc, Moreno-España José, Capuron Lucile, Navinés Ricard, Farré Magí, Vieta Eduard, Martín-Santos Rocio
Department of Psychiatry, Hospital Clínic, IDIBAPS, CIBERSAM; and Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Catalonia, Spain. Villarroel, 170; 08036-Barcelona, Catalonia, Spain.
CNS Neurol Disord Drug Targets. 2014;13(6):1066-74. doi: 10.2174/1871527313666140612121921.
Current treatments of depression include psychological, pharmacological and physical approaches. Pharmacological interventions to treat depression have previously focused on modifying dysfunctional neurotransmitter systems. Overall, these treatments have demonstrated an ability to manage major depression but otucomes continue to be poor in many patients, especially those with long term illness or with previous multiple relapses. This may be due to the fact that depression is a systemic and neuroprogressive illness involving multiple biological pathways such as immunological factors. There is substantial evidence that cytokine therapies induce depressive symptoms in clinical populations. The model of cytokine-induced depression has provided important information relative to the risk factors and biological pathways involved in the etiology of depressive symptoms and, most importantly, the identification and knowledge of these factors has allowed new treatment targets to be explored. When an exogenous cytokine such as interferon-alpha is administered, proinflammatory cytokines are activated, leading to alterations in neurotransmission and endocrine pathways and producing neurotoxicity. Several new treatments for depression acting through pathways other than amine neurotransmission have emerged in recent years. The regulation of the inflammatory response, the decrease in the activity of the hypothalamic-pituitary-adrenal axis and the prevention of neurotoxicity are potential targets for new drugs. Though these drugs are mostly at the proof-of-concept stage, some of them have already shown promising results for the treatment of depression.
目前抑郁症的治疗方法包括心理、药物和物理方法。以往治疗抑郁症的药物干预主要集中在调节功能失调的神经递质系统。总体而言，这些治疗方法已显示出治疗重度抑郁症的能力，但许多患者的治疗效果仍然不佳，尤其是那些患有长期疾病或既往有多次复发的患者。这可能是因为抑郁症是一种全身性的神经进行性疾病，涉及多种生物学途径，如免疫因素。有大量证据表明，细胞因子疗法会在临床人群中诱发抑郁症状。细胞因子诱导的抑郁症模型提供了与抑郁症状病因相关的危险因素和生物学途径的重要信息，最重要的是，对这些因素的识别和了解使得能够探索新的治疗靶点。当给予外源性细胞因子如α干扰素时，促炎细胞因子被激活，导致神经传递和内分泌途径改变并产生神经毒性。近年来出现了几种通过胺类神经传递以外的途径治疗抑郁症的新方法。调节炎症反应、降低下丘脑-垂体-肾上腺轴的活性以及预防神经毒性是新药的潜在靶点。尽管这些药物大多处于概念验证阶段，但其中一些已显示出治疗抑郁症的 promising results。 （注：原文中“otucomes”应改为“outcomes”，“promising results”直译为“有希望的结果”，结合语境这里可灵活翻译为“有前景的效果”等更通顺的表达，这里保留了原文的错误单词和不太符合中文习惯的表述方式）
