Heightened risk: Childhood trauma and anticipatory grief exacerbate the impact of loneliness on depressive symptoms and LPS-stimulated cytokines in dementia caregivers

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

doi:10.1016/j.psyneuen.2025.107523

Heightened risk: Childhood trauma and anticipatory grief exacerbate the impact of loneliness on depressive symptoms and LPS-stimulated cytokines in dementia caregivers

Psychoneuroendocrinology. 2025 Jun 18:179:107523. doi: 10.1016/j.psyneuen.2025.107523. Online ahead of print.

Authors

Affiliations

¹ Department of Psychological Sciences, Rice University, USA; Institute of Health Resilience and Innovation, Rice University, USA. Electronic address: kb110@rice.edu.
² Department of Psychology, Portland State University, USA.
³ Department of Psychological Sciences, Rice University, USA.
⁴ Department of Psychological Sciences, Rice University, USA; Institute of Health Resilience and Innovation, Rice University, USA.
⁵ Department of Psychology, Texas Christian University, USA.
⁶ McGovern Medical School, University of Texas Health Science Center Houston, USA.
⁷ Department of Psychology, University of Houston, USA.
⁸ Department of Psychiatry, Cambridge Health Alliance, USA; Department of Psychiatry, Harvard Medical School, USA.
⁹ Department of Neurology, Baylor College of Medicine, USA; Institute of Health Resilience and Innovation, Rice University, USA.
¹⁰ Department of Psychological Sciences, Rice University, USA; Department of Psychiatry, Baylor College of Medicine, USA.
¹¹ Department of Psychological Sciences, Rice University, USA; Department of Psychology, University of Houston, USA; Department of Psychiatry, Baylor College of Medicine, USA; Department of Behavioral Science, MD Anderson Cancer Center, USA; Institute of Health Resilience and Innovation, Rice University, USA.

PMID: 40554993
DOI: 10.1016/j.psyneuen.2025.107523

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: Anticipatory grief; Childhood trauma; Dementia spousal caregivers; Inflammation; Loneliness; Sleep quality.