Phillips Mary L, Chase Henry W, Sheline Yvette I, Etkin Amit, Almeida Jorge R C, Deckersbach Thilo, Trivedi Madhukar H
From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; the Department of Psychiatry, Massachusetts General Hospital, Boston; and the Department of Psychiatry, UT Southwestern Medical Center, Dallas.
Am J Psychiatry. 2015 Feb 1;172(2):124-38. doi: 10.1176/appi.ajp.2014.14010076.
Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder.
In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes.
The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression.
Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes.
尽管神经科学和治疗方法有了显著进展，但仍没有广泛认可的生物标志物可用于指导重度抑郁症患者的诊断或确定首选治疗方法。
在这篇批判性综述中，作者探讨了多模态神经成像技术在多大程度上能够识别反映抑郁症关键病理生理过程的生物标志物，以及这些生物标志物是否可以作为治疗反应的预测因子、调节因子和中介因子，从而基于对这些过程的更好理解促进个性化治疗的发展。
作者首先强调了抑郁症神经成像研究中使用不同技术得出的最一致的发现，包括两个平行神经回路中的结构和功能异常：以杏仁核和内侧前额叶皮质的不同区域为中心的血清素调节的内隐情绪调节回路；以及以腹侧纹状体和内侧前额叶皮质为中心的多巴胺调节的奖赏神经回路。然后，他们描述了相对较少的研究中的关键发现，这些研究表明这些神经回路中区域功能的特定测量指标，以及在较小程度上结构指标，可以预测抑郁症的治疗反应。
现有研究的局限性包括样本量小、仅使用一种神经成像模式，以及专注于识别预测因子而非不同治疗反应的调节因子和中介因子。通过解决这些局限性，最重要的是利用多模态神经成像的优势，未来的研究可以得出抑郁症治疗反应的调节因子和中介因子，以促进短期和长期临床及功能结果的显著改善。
