Mood and Anxiety Division and Research Imaging Centre, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Clin Pharmacol Ther. 2012 Feb;91(2):201-14. doi: 10.1038/clpt.2011.285. Epub 2012 Jan 4.
It is estimated that 15% of all individuals will experience a major depressive episode (MDE) during their lifetime and that treatment response is inadequate in 40% of these cases. To address this, neuroimaging is being used to identify MDE subtypes and mechanisms of onset as well as to optimize target occupancy of novel treatments. Neuroimaging of monoamine oxidase-A (MAO-A) binding; glutamate levels; indexes of 5-HT(2A), 5-HTT, 5-HT(1A), and 5-HT(1B) receptors; levels of dopamine transporters D(1) and D(2); and hippocampal volume are described here. Three themes emerge. First, symptoms such as pessimism, motor retardation, anxiety disorder, and verbal memory deficits best indicate the subtype of depression. Second, measures related to mechanisms of monoamine loss, particularly elevated MAO-A binding in prefrontal and anterior cingulate cortex, are present in MDE and in high-risk states for MDE. Third, clinical trials show a consistent 80% 5-HTT occupancy of selective serotonin reuptake inhibitors at doses sufficient to distinguish from placebo in clinical trials (although in vitro affinities vary 100-fold), thereby supporting the need for further occupancy studies to accelerate therapeutic development.
据估计，所有个体中有 15%会在其一生中经历一次重度抑郁发作（MDE），而这些病例中有 40%的治疗反应不足。为了解决这个问题，神经影像学被用于识别 MDE 亚型和发病机制，以及优化新型治疗的靶区占有率。本文描述了单胺氧化酶-A（MAO-A）结合；谷氨酸水平；5-HT（2A）、5-HTT、5-HT（1A）和 5-HT（1B）受体的指数；多巴胺转运体 D（1）和 D（2）的水平；以及海马体积的神经影像学。有三个主题出现。首先，悲观、运动迟缓、焦虑障碍和言语记忆缺陷等症状最能表明抑郁症的亚型。其次，与单胺丢失机制相关的措施，特别是前额叶和前扣带皮层中升高的 MAO-A 结合，在 MDE 和 MDE 的高风险状态中存在。第三，临床试验显示，选择性 5-羟色胺再摄取抑制剂在足以与安慰剂区分的剂量下，其 5-HTT 占有率一致达到 80%（尽管体外亲和力相差 100 倍），因此需要进一步的占有率研究来加速治疗的发展。
