Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, One Bowdoin Square, Boston, MA 02114, USA.
Int J Neuropsychopharmacol. 2012 Jul;15(6):841-54. doi: 10.1017/S1461145711001246. Epub 2011 Aug 4.
Major depressive disorder (MDD) is a common medical illness affecting millions worldwide. Despite their widespread use since the 1950s and 1960s, the 'downstream' mechanism by which antidepressants ultimately exert their therapeutic effects remains elusive. In addition, except for a few exceptions such as episode severity and the presence of comorbid Axis-I or Axis-III disorders, biological or clinical characteristics which can accurately quantify the risk of poor treatment outcome are lacking, as are factors which could help patients and clinicians select treatment options that would result in superior outcome. The identification of such markers, termed 'surrogate' markers, could help shed further insights into what constitutes illness and recovery, help identify molecular targets for the development of future antidepressants, and lead the way to the design and refinement of a personalized medicine treatment model for MDD. In the following text, several major areas ('leads') where evidence exists regarding the presence of surrogate markers of efficacy outcome in MDD will be briefly reviewed. Leads include evidence from the role of demographic and clinical factors as surrogate markers, to the role of various biological markers including genotype, brain functional imaging, electroencephalography, dichotic listening, and molecular biology and immunology. The purpose of this work is to focus selectively on areas where there have been findings, as opposed to conducting an exhaustive literature review of studies which have failed to yield any significant breakthrough in our knowledge.
重度抑郁症（MDD）是一种常见的影响全球数百万人的医学疾病。尽管自 20 世纪 50 年代和 60 年代以来广泛使用，但抗抑郁药最终发挥治疗作用的“下游”机制仍然难以捉摸。此外，除了一些例外，如发作严重程度和共病轴 I 或轴 III 障碍的存在，缺乏能够准确量化治疗结果不良风险的生物学或临床特征，也缺乏可以帮助患者和临床医生选择治疗方案的因素，这些治疗方案将导致更好的结果。这些标志物被称为“替代”标志物，其鉴定可以帮助进一步了解疾病和康复的构成，有助于确定未来抗抑郁药开发的分子靶标，并为 MDD 的个性化医学治疗模式的设计和改进铺平道路。在下面的文本中，将简要回顾 MDD 中存在疗效替代标志物的几个主要领域（“线索”）。线索包括人口统计学和临床因素作为替代标志物的作用的证据，以及各种生物标志物的作用，包括基因型、脑功能成像、脑电图、双耳分听、分子生物学和免疫学。这项工作的目的是有选择地关注已经有发现的领域，而不是对那些未能在我们的知识中取得任何重大突破的研究进行详尽的文献综述。
