Boukezzi Sarah, Costi Sara, Shin Lisa M, Kim-Schulze Seunghee, Cathomas Flurin, Collins Abigail, Russo Scott J, Morris Laurel S, Murrough James W
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychology, Tufts University, Medford, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Brain Behav Immun. 2022 Aug;104:205-212. doi: 10.1016/j.bbi.2022.05.015. Epub 2022 May 27.
Depression is characterized by altered neurobiological responses to threat and inflammation may be involved in the development and maintenance of symptoms. However, the mechanistic pathways underlying the relationship between the neural underpinnings of threat, inflammation and depressive symptoms remain unknown.
Twenty participants with major depressive disorder (MDD) and 17 healthy controls (HCs) completed this study. Peripheral blood mononuclear cells (PBMCs) were collected and stimulated ex vivo with lipopolysaccharide (LPS). We then measured a broad array of secreted proteins and performed principal component analysis to compute an aggregated immune reactivity score. Subjects completed a well-validated emotional face processing task during functional magnetic resonance imaging (fMRI). Amygdala activation was measured during perception of threat for the main contrast of interest: fear > happy face. Participants completed the Mood and Anxiety Symptom Questionnaire (MASQ) and the Perceived Stress Scale (PSS). Correlation analyses between amygdala activation, the aggregate immune score, and symptom were computed across groups. A mediation analysis was also performed across groups to further explore the relationship between these three variables.
In line with our hypotheses and with prior work, the MDD group showed greater amygdala activation in response to threat compared to the HC group [t = -2.038, p = 0.049]. Internal consistency of amygdala activation to threat was found to be moderate. Response to an ex vivo immune challenge was greater in MDD than HC based on the computed immune reactivity score (PC1; t = 2.674, p = 0.011). Amygdala activation was positively correlated with the immune score (r = 0.331, p = 0.045). Moreover, higher amygdala activation was associated with greater anxious arousal measured by the MASQ (r = 0.390, p = 0.017). Exploring the role of stress, we found that higher perceived stress was positively associated with both inflammatory response (r = 0.367, p = 0.026) and amygdala response to threat (r = 0.325, p = 0.050). Mediation analyses showed that perceived stress predicted anxious arousal, but neither inflammation nor amygdala activation fully accounted for the effect of perceived stress on anxious arousal.
These data highlight the potential importance of threat circuitry hyperactivation in MDD, consistent with prior reports. We found that higher levels of inflammatory biomarkers were associated with higher amygdala activation, which in turn was associated with anxious arousal. Future research utilizing larger sample sizes are needed to replicate these preliminary results.
抑郁症的特征是对威胁的神经生物学反应改变，炎症可能参与症状的发生和维持。然而，威胁、炎症和抑郁症状之间关系的潜在机制尚不清楚。
20名重度抑郁症（MDD）患者和17名健康对照者（HCs）完成了本研究。采集外周血单核细胞（PBMC），并在体外使用脂多糖（LPS）进行刺激。然后，我们测量了一系列分泌蛋白，并进行主成分分析以计算综合免疫反应性评分。受试者在功能磁共振成像（fMRI）期间完成了一项经过充分验证的情绪面孔加工任务。在对主要感兴趣的对比（恐惧>快乐面孔）进行威胁感知期间测量杏仁核激活。参与者完成了情绪和焦虑症状问卷（MASQ）和感知压力量表（PSS）。计算两组间杏仁核激活、综合免疫评分和症状之间的相关性分析。还对两组进行了中介分析，以进一步探讨这三个变量之间的关系。
与我们的假设和先前的研究一致，MDD组在面对威胁时杏仁核激活程度高于HC组[t = -2.038，p = 0.049]。发现杏仁核对威胁的激活内部一致性为中等。根据计算的免疫反应性评分（PC1；t = 2.674，p = 0.011），MDD组对体外免疫挑战的反应比HC组更大。杏仁核激活与免疫评分呈正相关（r = 0.331，p = 0.045）。此外，杏仁核激活程度越高，通过MASQ测量的焦虑唤醒程度越高（r = 0.390，p = 0.017）。在探索压力的作用时，我们发现较高的感知压力与炎症反应（r = 0.367，p = 0.026）和杏仁核对威胁的反应均呈正相关（r = 0.325，p = 0.050）。中介分析表明，感知压力可预测焦虑唤醒，但炎症和杏仁核激活均不能完全解释感知压力对焦虑唤醒的影响。
这些数据突出了MDD中威胁回路过度激活的潜在重要性，与先前的报道一致。我们发现较高水平的炎症生物标志物与较高的杏仁核激活相关，而杏仁核激活又与焦虑唤醒相关。需要未来使用更大样本量的研究来重复这些初步结果。
