Heightened Risk: Childhood Trauma and Anticipatory Grief Exacerbate the Impact of Loneliness on Depressive Symptoms and Lps-Stimulated Cytokines in Dementia Caregivers

Authors

Kelly N Brice
Jensine Paoletti-Hatcher
E Lydia Wu-Chung
Vincent D Lai
Daniel L Argueta
Michelle A Chen
Itee Mahant
Bryan T Denny
Charles Green
Luis D Medina
Paul Schulz
Jennifer Stinson
Samantha K Henry
Cobi Heijnen
Christopher P Fagundes

Publication Date

9-1-2025

Journal

Psychoneuroendocrinology

DOI

10.1016/j.psyneuen.2025.107523

PMID

40554993

PMCID

PMC12273704

PubMedCentral® Posted Date

7-18-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Dementia spousal caregivers are at a disproportionate risk for adverse mental and physical health outcomes. Loneliness is associated with depressive symptoms and proinflammatory cytokine production among caregivers. Additionally, childhood trauma, anticipatory grief, and poor sleep quality are all associated with enhanced stress reactivity. This study used a cross-sectional design to investigate whether loneliness is associated with proinflammatory cytokine production and depressive symptoms in caregivers, and whether these relationships are strongest among caregivers who report high levels of childhood trauma, high amounts of anticipatory grief, or poor sleep quality. A sample of 111 dementia spousal caregivers provided blood samples and completed self-report measures of loneliness, childhood trauma, anticipatory grief, depression, and subjective sleep quality. We measured the ex vivo immune cell proinflammatory cytokine response to whole-blood LPS stimulation. Caregivers who reported greater loneliness exhibited elevated LPS-stimulated proinflammatory cytokine production and more depressive symptoms. The relationship between loneliness and proinflammatory cytokine production was stronger at higher levels of childhood trauma and higher levels of anticipatory grief. The association between loneliness and depressive symptoms was stronger at higher levels of childhood trauma and higher levels of anticipatory grief. These results suggest that loneliness could have more robust effects on adverse health outcomes for caregivers who have experienced more childhood trauma and anticipatory grief. This research contributes to the existing literature investigating the mechanisms that underlie individual differences in health outcomes among dementia spousal caregivers.

Keywords

Humans, Loneliness, Male, Female, Dementia, Caregivers, Depression, Grief, Middle Aged, Cross-Sectional Studies, Aged, Lipopolysaccharides, Cytokines, Adult, Adverse Childhood Experiences, Aged, 80 and over, Stress, Psychological

Published Open-Access

yes

Recommended Citation

Brice, Kelly N; Paoletti-Hatcher, Jensine; Wu-Chung, E Lydia; et al., "Heightened Risk: Childhood Trauma and Anticipatory Grief Exacerbate the Impact of Loneliness on Depressive Symptoms and Lps-Stimulated Cytokines in Dementia Caregivers" (2025). Faculty, Staff and Student Publications. 4990.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4990