Whole Blood Serotonin Levels in Healthy Elderly are Negatively Associated with the Functional Activity of Emotion-related Brain Regions

Understanding the role of neuromodulators of socio-affective processing is important to ensure psychological wellbeing during older years. To assess the potential implication of serotonin levels in socio-affective processing in older adults, this study investigated the link between peripheral measures of serotonin (i.e., whole blood) and brain and behavioral responses to emotional information in healthy elderly (N =119). A priori regions of interest (ROI) were selected due to both their role in emotion processing and their dense serotonergic innervation (i.e., amygdalae, insulae, dorsal anterior cingulate cortex and subgenual cingulate gyrus). Brain responses to emotional information were computed as the ROI-specific difference between in functional brain activity to high vs. low emotional videos. The same procedure was carried out for the subsequent resting periods. Zero-order and partial correlation analyses were performed between these ROI-specific increases in brain activations and whole blood serotonin levels. Significant negative associations were observed between serotonin and functional activity for the bilateral insula, dorsal anterior cingulate cortex and subgenual gyrus. The results were replicated by confirmatory voxel-wise analyses, highlighting the specificity of the findings. These effects were only present during the videos, but not in the resting periods. There were no associations between 5-HT levels and behavioral measures of socio-affective functions. Our results mirror pharmacological and genetic studies showing that changes in the serotonergic system may lead to enhanced emotional brain responses. Given the involvement of serotonin in a wide range of age-related changes, our study sets the basis for future research aiming to characterize the role of this endogenous modulator in emotion processing of elderly populations.阐明社会情感加工的神经调节因子的作用，对于保障老年人的心理健康福祉至关重要。为评估5-羟色胺(serotonin)水平对老年人社会情感加工的潜在影响，本研究针对119名健康老年人，探究了5-羟色胺的外周检测指标（即全血样本）与情绪信息刺激下的脑活动及行为反应之间的关联。本研究预先选定了感兴趣区(ROI)，这些脑区既参与情绪加工，同时也接受密集的5-羟色胺能神经支配，具体包括双侧杏仁核、双侧脑岛、背侧前扣带回皮层与扣带回下膝部皮层。针对情绪信息的脑活动反应，通过计算各感兴趣区在高情绪唤醒度与低情绪唤醒度视频刺激下的脑功能活动差值得到。后续的静息态扫描时段也采用了相同的处理流程。本研究针对各感兴趣区的脑激活增幅与全血5-羟色胺水平，开展了零阶相关与偏相关分析。研究发现，双侧脑岛、背侧前扣带回皮层以及扣带回下膝部皮层的脑功能活动与5-羟色胺水平之间存在显著负相关。验证性逐体素分析重复了上述结果，进一步凸显了本研究发现的特异性。上述效应仅在视频刺激时段显著，静息态时段未观察到相关关联。全血5-羟色胺水平与社会情感功能的行为学评估指标之间未发现显著关联。本研究结果与此前药理学及遗传学研究的结论相互印证，后者表明5-羟色胺能系统的改变可能会增强情绪相关的脑活动反应。鉴于5-羟色胺参与多种年龄相关的生理与心理变化，本研究为后续探索该内源性调节因子在老年群体情绪加工中的作用奠定了坚实基础。