Schneider Max, Elbau Immanuel G, Nantawisarakul Teachawidd, Pöhlchen Dorothee, Brückl Tanja, Czisch Michael, Saemann Philipp G, Lee Michael D, Binder Elisabeth B, Spoormaker Victor I
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Department of Cognitive Sciences, University of California, Irvine, CA 92697-5100, USA.
Brain Sci. 2020 Nov 25;10(12):906. doi: 10.3390/brainsci10120906.
Depression is a debilitating disorder with high prevalence and socioeconomic cost, but the brain-physiological processes that are altered during depressive states are not well understood. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. We translated these findings to human subjects with concomitant pupillometry/fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls. We could show that the upregulation and maintenance of arousal in anticipation of reward was disrupted in patients in a symptom-load dependent manner. We could further show that the failure to maintain reward anticipatory arousal showed state-marker properties, as it tracked the load and impact of depressive symptoms independent of prior diagnosis status. Further, group differences of anticipatory arousal and continuous correlations with symptom load were not traceable only at the level of pupillometric responses, but were mirrored also at the neural level within salience network hubs. The upregulation and maintenance of arousal during reward anticipation is a novel translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification and targeted interventions.
抑郁症是一种患病率高且社会经济成本高昂的致残性疾病，但人们对抑郁状态下发生改变的脑生理过程了解甚少。在此，我们基于猕猴最近的研究发现展开，这些发现表明在奖励预期期间瞳孔扩张与前扣带回皮层介导的唤醒之间存在直接因果关系。我们将这些发现应用于人类受试者，在一组被诊断为重度抑郁症的未用药参与者和健康对照样本中同时进行瞳孔测量/功能磁共振成像。我们能够证明，在奖励预期期间唤醒的上调和维持在患者中以症状负荷依赖的方式受到破坏。我们还能够进一步证明，无法维持奖励预期唤醒具有状态标记特性，因为它跟踪抑郁症状的负荷和影响，而与先前的诊断状态无关。此外，预期唤醒的组间差异以及与症状负荷的持续相关性不仅在瞳孔测量反应水平上可追溯，在突显网络枢纽的神经水平上也有体现。奖励预期期间唤醒的上调和维持是一个新的可转化且易于追踪的过程，可能为基于生理的患者分层和靶向干预提供一个有前景的途径。
