Loneliness predicts pain, depression, and fatigue: understanding the role of immune dysregulation

Psychoneuroendocrinology. 2013 Aug;38(8):1310-7. doi: 10.1016/j.psyneuen.2012.11.016. Epub 2012 Dec 27.


Objective: The pain, depression, and fatigue symptom cluster is an important health concern. Loneliness is a common risk factor for these symptoms. Little is known about the physiological mechanisms linking loneliness to the symptom cluster; immune dysregulation is a promising candidate. Latent herpesvirus reactivation, which is reflected by elevated herpesvirus antibody titers, provides a window into immune dysregulation. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are two common herpesviruses.

Methods: Participants were 200 breast cancer survivors who were 2 months to 3 years post-treatment at the time of the study. They completed questionnaires and provided a blood sample that was assayed for CMV and EBV antibody titers.

Results: Lonelier participants experienced more pain, depression, and fatigue than those who felt more socially connected. Lonelier participants also had higher CMV antibody titers which, in turn, were associated with higher levels of the pain, depression, and fatigue symptom cluster. Contrary to expectations, EBV antibody titers were not associated with either loneliness or the symptom cluster.

Conclusions: The pain, depression, and fatigue symptom cluster is a notable clinical problem, especially among cancer survivors. Accordingly, understanding the risk factors for these symptoms is important. The current study suggests that loneliness enhances risk for immune dysregulation and the pain, depression, and fatigue symptom cluster. The present data also provide a glimpse into the pathways through which loneliness may impact health.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Breast Neoplasms / immunology
  • Breast Neoplasms / psychology
  • Cytomegalovirus / immunology*
  • Depression / complications
  • Depression / immunology*
  • Depression / psychology
  • Fatigue / complications
  • Fatigue / immunology*
  • Fatigue / psychology
  • Female
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Loneliness / psychology*
  • Middle Aged
  • Pain / complications
  • Pain / immunology*
  • Pain / psychology
  • Survivors / psychology


  • Antibodies, Viral