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Amygdala-Centered Emotional Processing in Prolonged Grief Disorder: Relationship With Clinical Symptomatology
Gyujoon Hwang1, Nutta-On P Blair1, B Douglas Ward1
1Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Background:
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.
Methods:
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.
Results:
The PGD group showed higher right amygdala activation to negative emotional stimuli than the integrated grief group (pcorrected < .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 (pcorrected < .05), which negatively correlated with avoidance of loss reminders. Resting-state FC between the identified right amygdala and thalamus was higher in PGD (pcorrected < .05), which negatively correlated with loneliness.
Conclusions:
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.
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