Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
Transl Psychiatry. 2023 May 11;13(1):165. doi: 10.1038/s41398-023-02440-3.
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-HT receptor (5-HTR) 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-HTR 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 [C]SB207145 positron emission tomography (PET) scan to quantify 5-HTR binding (BP) and a functional magnetic resonance imaging (fMRI) scan during which they performed an emotional face matching task. We examined the association between regional 5-HTR 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-HTR BP 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-HTR binding and neural responses to emotions that appear unaltered in MDD. Future clinical trials with novel pharmacological agents targeting 5-HTR are needed to confirm whether they ameliorate emotion processing biases in MDD.
脑内 5-羟色胺（5-HT）信号被认为可以调节对情绪刺激的神经反应。5-HT 信号功能障碍与重度抑郁症（MDD）有关，MDD 患者存在明显的情绪处理障碍。在 MDD 中，最近的证据表明 5-HT 受体（5-HTR）水平改变，这是抗抑郁治疗的一个有希望的靶点。然而，这些改变如何影响 MDD 患者的情绪神经处理仍知之甚少。这是第一项研究，旨在检查 MDD 患者和健康对照组中 5-HTR 结合与情绪神经反应之间的关系。该研究纳入了 138 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 名健康对照者。参与者接受了 [C]SB207145 正电子发射断层扫描（PET）扫描，以量化 5-HTR 结合（BP），并进行功能磁共振成像（fMRI）扫描，在此期间他们执行了情绪面孔匹配任务。我们使用线性潜在变量模型检查了区域 5-HTR 结合与皮质边缘系统对情绪面孔的反应之间的关系，包括这种关系是否受到抑郁状态的调节。我们观察到，在所有参与者中，5-HTR BP 与皮质边缘系统对情绪面孔的反应之间存在正相关（r=0.20，p=0.03）。在两组之间，这种相关性没有差异（参数估计差异=0.002，95%CI=-0.008：0.013，p=0.72）。因此，在最大的 5-HT 信号与大脑功能之间关联的 PET/fMRI 研究中，我们发现 5-HTR 结合与对情绪的神经反应之间存在正相关，而在 MDD 中，这种相关性似乎没有改变。需要新的针对 5-HTR 的药理学药物进行临床试验，以确认它们是否能改善 MDD 患者的情绪处理偏差。
