Loneliness as a driver of allostatic load: mechanisms linking social disconnection to physiological dysregulation and health disparities

Document Type

Journal Article

Publication Date

12-31-2025

Journal

Stress (Amsterdam, Netherlands)

Volume

28

Issue

1

DOI

10.1080/10253890.2025.2594067

Keywords

Loneliness; allostatic load; inflammation; perceived isolation; social isolation; stress response

Abstract

Loneliness is increasingly recognized as a multisystem stressor that contributes to morbidity and premature mortality. This narrative review draws on searches of PubMed, PsycINFO, and Scopus (2000-2025), focusing on studies linking loneliness to neuroendocrine, immune, neural, and cardiometabolic pathways associated with allostatic load. Evidence is strongest in older adults and clinical subgroups, though emerging findings suggest relevance and mechanistic insight across community populations. Loneliness is associated with dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, elevated inflammatory biomarkers, altered amygdala reactivity, and cardiometabolic risk factors. These patterns highlight loneliness as both a psychological and biological risk factor. Limitations include heterogeneous measures and reliance on cross-sectional designs, underscoring the need for longitudinal and mechanistic studies. Addressing loneliness requires early detection through screening and implementation of evidence-based interventions, including psychosocial therapies (e.g. cognitive-behavioral and mindfulness-based approaches), social prescribing, and trauma-informed primary care. Reframing loneliness as a modifiable determinant of health underscores its importance for translational research, clinical care, and public health policy.

Department

Clinical Research and Leadership

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