Amygdala-centered emotional processing in Prolonged Grief Disorder: Relationship with clinical symptomatology

Gyujoon Hwang; Nutta-On P Blair; B Douglas Ward; Timothy L McAuliffe; Stacy A Claesges; Abigail R Webber; Keri R Hainsworth; Yang Wang; Charles F Reynolds; Elliot A Stein; Joseph S Goveas

doi:10.1016/j.bpsc.2024.12.008

Amygdala-centered emotional processing in Prolonged Grief Disorder: Relationship with clinical symptomatology

Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Dec 24:S2451-9022(24)00384-7. doi: 10.1016/j.bpsc.2024.12.008. Online ahead of print.

Affiliations

¹ Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
² Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
³ Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴ Department of Psychiatry, University of Pittsburgh School of Medicine, PA, USA.
⁵ National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA.
⁶ Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: [email protected].

PMID: 39725082
DOI: 10.1016/j.bpsc.2024.12.008

Abstract

Background: Prolonged Grief Disorder 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 (61.5±8.9 years old) experiencing probable Prolonged Grief Disorder (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 fMRI scanning, and 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, compared to the integrated grief group (p_corr<0.05), which positively correlated with intrusive thoughts. Generalized psychophysiological interaction analysis revealed lower task-dependent functional connectivity between the right amygdala and posterior cingulate cortex/precuneus in PGD (p_corr<0.05), which negatively correlated with avoidance of loss reminders. Resting-state functional connectivity between the identified right amygdala and thalamus was higher in PGD (p_corr<0.05), which negatively correlated with loneliness.

Conclusions: Dysregulated amygdala-centric neural activity and functional connectivity during processing of negative affective stimuli and at rest appear to differentiate prolonged from integrated grief in older adults. Future investigations using interventions to target amygdala-centric neural circuit abnormalities may provide new insights into the role of enhanced negative bias and related mechanisms underlying PGD and support treatment efficacy.