Relationship Between Social Isolation, Loneliness, and Systemic Inflammation: A Scoping Review of Biological Signatures and Clinical Outcomes.
4 affiliations
- 1School of Medicine, University of Crete, 71003 Heraklion, Greece.
- 2School of Medicine, University Hospital and University of Crete, 70013 Heraklion, Greece.
- 3Department of Social Medicine, School of Medicine, University of Crete, 70013 Heraklion, Greece.
- 4Community Pharmacists Association of Heraklion, 71201 Heraklion, Greece.
Abstract
Background
Social isolation and loneliness are established social determinants of health, associated with 25-30% higher mortality risk, yet their relationship with systemic inflammation and broader biological and clinical outcomes has not been comprehensively synthesized across life stages.Methods
PubMed/MEDLINE, Scopus, and ScienceDirect were searched (2015-2025), supplemented by citation searching and a targeted supplementary search, for human studies linking social isolation, loneliness, or social connectedness to inflammatory biomarkers or biological/clinical outcomes. PRISMA-ScR guidance was followed; findings were synthesized narratively across five thematic axes as an evidence map.Results
Of 3351 records identified, 73 studies were included. Isolation was most often associated with CRP and fibrinogen, and loneliness with IL-6. Isolation predicted sarcopenia, venous thromboembolism, pancreatic cancer, and cardiovascular disease, with inflammatory or metabolic markers mediating a modest (≈5-19%) share. Proteomic (n = 42,062) and epigenetic analyses linked loneliness to inflammatory, antiviral, and complement-pathway proteins and to accelerated epigenetic ageing; Mendelian randomization supported causal involvement of several proteins. Social connectedness and relationship quality tracked with lower IL-6 and better functional indices. Evidence was strongest in midlife and older cohorts.Conclusions
Social disconnection shows biologically plausible but heterogeneous associations with inflammatory and molecular signatures; harmonized measurement and prospective, hypothesis-free omics designs are needed to clarify causality and inform targeted screening.
Related
- Social isolation, self-perceived loneliness, and the 7-year trajectories of depression and cognitive decline: a prospective cohort study
- Chronic loneliness and isolation phenotypes and physical and mental health in older adults
- The underlying neurobiology of social isolation and loneliness in middle-older adults: A systematic review.
- Social isolation, loneliness and subsequently developing risk for autoimmune diseases: A prospective study from UK Biobank
- Emotion Regulation Difficulties and Rumination as Serial Mediators in the Relationship Between Psychological Resilience and Loneliness
BibTeX
@article{bechliouli2026relationship,
title = {{Relationship Between Social Isolation, Loneliness, and Systemic Inflammation: A Scoping Review of Biological Signatures and Clinical Outcomes.}},
author = {Aimilia Bechliouli and Dimitrios Stylianakis and Marios Spanakis and Christos Lionis and Emmanouil K Symvoulakis},
journal = {Diseases (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/diseases14100388},
url = {https://europepmc.org/article/MED/42930015},
note = {CC BY},
}
RIS
TY - JOUR
TI - Relationship Between Social Isolation, Loneliness, and Systemic Inflammation: A Scoping Review of Biological Signatures and Clinical Outcomes.
AU - Aimilia Bechliouli
AU - Dimitrios Stylianakis
AU - Marios Spanakis
AU - Christos Lionis
AU - Emmanouil K Symvoulakis
PY - 2026
DA - 2026/10/21
JO - Diseases (Basel, Switzerland)
DO - 10.3390/diseases14100388
UR - https://europepmc.org/article/MED/42930015
AB - Background Social isolation and loneliness are established social determinants of health, associated with 25-30% higher mortality risk, yet their relationship with systemic inflammation and broader biological and clinical outcomes has not been comprehensively synthesized across life stages.Methods PubMed/MEDLINE, Scopus, and ScienceDirect were searched (2015-2025), supplemented by citation searching and a targeted supplementary search, for human studies linking social isolation, loneliness, or social connectedness to inflammatory biomarkers or biological/clinical outcomes. PRISMA-ScR guidance was followed; findings were synthesized narratively across five thematic axes as an evidence map.Results Of 3351 records identified, 73 studies were included. Isolation was most often associated with CRP and fibrinogen, and loneliness with IL-6. Isolation predicted sarcopenia, venous thromboembolism, pancreatic cancer, and cardiovascular disease, with inflammatory or metabolic markers mediating a modest (≈5-19%) share. Proteomic (n = 42,062) and epigenetic analyses linked loneliness to inflammatory, antiviral, and complement-pathway proteins and to accelerated epigenetic ageing; Mendelian randomization supported causal involvement of several proteins. Social connectedness and relationship quality tracked with lower IL-6 and better functional indices. Evidence was strongest in midlife and older cohorts.Conclusions Social disconnection shows biologically plausible but heterogeneous associations with inflammatory and molecular signatures; harmonized measurement and prospective, hypothesis-free omics designs are needed to clarify causality and inform targeted screening.
SN - 2079-9721
ER -