Hwang Gyujoon, Blair Nutta-On P, Ward B Douglas, McAuliffe Timothy L, Claesges Stacy A, Webber Abigail R, Hainsworth Keri R, Wang Yang, Reynolds Charles F, Stein Elliot A, Goveas Joseph S
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Dec 24. doi: 10.1016/j.bpsc.2024.12.008.
Prolonged grief disorder (PGD) is a multidimensional condition with adverse health consequences. We hypothesized that enhanced negative emotional bias characterizes this disorder and underlies its key clinical symptoms.
In a cross-sectional design, chronically grieving older adults (age 61.5 ± 8.9 years) experiencing probable PGD (n = 33) were compared with demographic- and time since loss-equated integrated (adaptive) grief participants (n = 38). To probe generalized negative affective reactivity, participants performed an emotional face-matching task during functional magnetic resonance imaging scanning and completed demographic and clinical assessments. Contrast maps (fearful + angry faces [-] shapes) were generated to determine group differences in brain activity within hypothesized affective and regulatory processing regions (amygdala, anterior insula, dorsal anterior cingulate, dorsolateral prefrontal cortex) and in exploratory whole-brain regression analyses.
The PGD group showed higher right amygdala activation to negative emotional stimuli than the integrated grief group (p < .05), which positively correlated with intrusive thoughts. Generalized psychophysiological interaction analysis revealed lower task-dependent functional connectivity (FC) between the right amygdala and posterior cingulate cortex/precuneus in PGD (p < .05), which negatively correlated with avoidance of loss reminders. Resting-state FC between the identified right amygdala and thalamus was higher in PGD (p < .05), which negatively correlated with loneliness.
Dysregulated amygdala-centric neural activity and FC during processing of negative affective stimuli and at rest appear to differentiate prolonged from integrated grief in older adults. Future investigations that use interventions to target amygdala-centric neural circuit abnormalities may provide new insights into the role of enhanced negative bias and related mechanisms that underlie PGD and support treatment efficacy.
持续性悲伤障碍（PGD）是一种具有不良健康后果的多维度病症。我们假设增强的负性情绪偏向是该障碍的特征，并构成其关键临床症状的基础。
采用横断面设计，将经历可能的PGD的慢性悲伤老年人（年龄61.5±8.9岁，n = 33）与在人口统计学和丧失时间方面匹配的整合性（适应性）悲伤参与者（n = 38）进行比较。为了探究广义的负性情感反应性，参与者在功能磁共振成像扫描期间执行了一项情绪面孔匹配任务，并完成了人口统计学和临床评估。生成对比图（恐惧+愤怒面孔[-]形状）以确定假设的情感和调节处理区域（杏仁核、前岛叶、背侧前扣带回、背外侧前额叶皮层）内的大脑活动的组间差异，并进行探索性全脑回归分析。
PGD组对负性情绪刺激的右侧杏仁核激活高于整合性悲伤组（p <.05），这与侵入性思维呈正相关。广义心理生理交互作用分析显示，PGD组右侧杏仁核与后扣带回皮层/楔前叶之间的任务依赖性功能连接（FC）较低（p <.05），这与避免丧失提醒呈负相关。PGD组中确定的右侧杏仁核与丘脑之间的静息态FC较高（p <.05），这与孤独感呈负相关。
在处理负性情感刺激期间以及静息状态下，以杏仁核为中心的神经活动和FC失调似乎可区分老年人的持续性悲伤与整合性悲伤。未来使用干预措施针对以杏仁核为中心的神经回路异常的研究可能会为增强的负性偏向以及构成PGD基础的相关机制的作用提供新见解，并支持治疗效果。
