Disrupted Large-Scale Brain Network Connectivity in Prolonged Grief Disorder: Relationship With Grief-Related Avoidance, Yearning, and Intrusive Thoughts

Nutta-On P Blair; Gyujoon Hwang; B Douglas Ward; Stacy A Claesges; Abigail R Webber; Keri R Hainsworth; Yang Wang; Charles F Reynolds 3rd; Elliot A Stein; Joseph S Goveas

doi:10.1016/j.bpsc.2025.07.011

Disrupted Large-Scale Brain Network Connectivity in Prolonged Grief Disorder: Relationship With Grief-Related Avoidance, Yearning, and Intrusive Thoughts

Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Aug 5:S2451-9022(25)00227-7. doi: 10.1016/j.bpsc.2025.07.011. Online ahead of print.

Affiliations

¹ Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
² Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
³ Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
⁴ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
⁵ National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland.
⁶ Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: jgoveas@mcw.edu.

PMID: 40769298
PMCID: PMC12346161 (available on 2026-08-05)
DOI: 10.1016/j.bpsc.2025.07.011

Abstract

Background: Large-scale brain network dysfunctions have been implicated in multiple neuropsychiatric disorders. Disrupted interactions between these networks may similarly underlie key symptoms in prolonged grief disorder (PGD).

Methods: In a cross-sectional functional magnetic resonance imaging study, resting-state functional connectivity (rsFC) between large-scale networks was compared in demographic- and time since loss-equated older adults with probable PGD (n = 42) and those with integrated grief (IG) (n = 45). Group independent component analysis revealed multiple networks, 8 of which (salience [SN], default mode [DMN], left and right executive control, ventral attention, dorsal attention, sensorimotor, and visual) were selected for further analyses, with rsFC strength between all network pairs computed. Networks with significant group differences were further assessed using fractional amplitude of low-frequency fluctuations (fALFF) to determine within-network differences. The relationships between connectivity measures and clinical symptoms were explored independently in the PGD and IG groups.

Results: Higher rsFC between SN and DMN was observed in the PGD group compared with the IG group (p_corrected = .014), which positively correlated with grief severity (p_corrected = .04) and grief-related avoidance (p_corrected = .04). In the PGD group, higher fALFF was observed in the DMN (p_uncorrected = .04), but not the SN. Principal component analysis revealed 4 symptom dimensions, with connectivity between multiple brain networks extending beyond the SN and DMN associated with an intrusive thoughts/yearning/avoidance component.

Conclusions: Aberrant connectivity between the SN and DMN appears to be a neurobiological correlate of grief severity and avoidance in PGD. Broader between-network connectivity disruptions correlate with intrusive thoughts, yearning, and avoidance, warranting further investigations into the mechanistic role of brain network dysfunction in PGD.

Keywords: Brain network; Depression; Grief; Older adults; Prolonged grief disorder; Resting-state fMRI.

Grants and funding

R01 MH122490/MH/NIMH NIH HHS/United States