PDF(Pubmed)
Abstract：
Brain serotonergic (5-HT) signaling is posited to modulate neural responses to emotional stimuli. Dysfunction in 5-HT signaling is implicated in major depressive disorder (MDD), a disorder associated with significant disturbances in emotion processing. In MDD, recent evidence points to altered 5-HT4 receptor (5-HT4R) levels, a promising target for antidepressant treatment. However, how these alterations influence neural processing of emotions in MDD remains poorly understood. This is the first study to examine the association between 5-HT4R binding and neural responses to emotions in patients with MDD and healthy controls. The study included one hundred and thirty-eight participants, comprising 88 outpatients with MDD from the NeuroPharm clinical trial (ClinicalTrials.gov identifier: NCT02869035) and 50 healthy controls. Participants underwent an [11C]SB207145 positron emission tomography (PET) scan to quantify 5-HT4R binding (BPND) and a functional magnetic resonance imaging (fMRI) scan during which they performed an emotional face matching task. We examined the association between regional 5-HT4R binding and corticolimbic responses to emotional faces using a linear latent variable model, including whether this association was moderated by depression status. We observed a positive correlation between 5-HT4R BPND and the corticolimbic response to emotional faces across participants (r = 0.20, p = 0.03). This association did not differ between groups (parameter estimate difference = 0.002, 95% CI = -0.008: 0.013, p = 0.72). Thus, in the largest PET/fMRI study of associations between serotonergic signaling and brain function, we found a positive association between 5-HT4R binding and neural responses to emotions that appear unaltered in MDD. Future clinical trials with novel pharmacological agents targeting 5-HT4R are needed to confirm whether they ameliorate emotion processing biases in MDD.
摘要：
脑5-羟色胺能（5-HT）信号传导被认为可以调节对情绪刺激的神经反应。5-HT信号的功能障碍与重度抑郁症（MDD）有关，与情绪处理中的显著障碍相关的障碍。在MDD中，最近的证据表明5-HT4受体（5-HT4R）水平改变，抗抑郁治疗的一个有希望的目标。然而,这些改变如何影响MDD中情绪的神经处理仍然知之甚少。这是第一项研究5-HT4R结合与MDD患者和健康对照者对情绪的神经反应之间的关联。这项研究包括一百三十八名参与者，包括来自NeuroPharm临床试验的88名MDD门诊患者（ClinicalTrials.gov标识符：NCT02869035）和50名健康对照。参与者进行了[11C]SB207145正电子发射断层扫描（PET）扫描以量化5-HT4R结合（BPND）和功能磁共振成像（fMRI）扫描，在此期间他们执行了情感面部匹配任务。我们使用线性潜在变量模型检查了区域5-HT4R结合与皮质对情绪面孔的反应之间的关联，包括这种关联是否受到抑郁状态的影响.我们观察到5-HT4RBPND与参与者对情绪面孔的皮质胶质反应之间呈正相关（r=0.20，p=0.03）。组间的这种关联没有差异(参数估计差异=0.002,95%CI=-0.008:0.013,p=0.72)。因此，在最大的PET/fMRI研究中，血清素能信号与脑功能之间的关联，我们发现5-HT4R结合和对情绪的神经反应呈正相关,而这些情绪在MDD中似乎没有改变.需要针对5-HT4R的新型药物的未来临床试验，以确认它们是否可以改善MDD中的情绪处理偏见。
