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A Systematic Review of the Association Between Bereavement and Biomarkers of Immune Function

Knowles, Lindsey M., MA; Ruiz, John M., PhD; O'Connor, Mary-Frances, PhD

doi: 10.1097/PSY.0000000000000693

Objective Bereavement is associated with increased risk for morbidity and all-cause mortality across epidemiological, meta-analytic, and case-control studies. The body of research examining the association between bereavement and immune function, beginning in 1977, has yet to be reviewed. The current systematic review clarifies these findings, identifies limitations of the diverse literature, and suggests a model and directions for future research.

Methods The PRISMA guidelines for systematic reviews were used to synthesize 41 years of research. Compared with a meta-analysis, a systematic review is appropriate given the heterogeneous nature of the studies. We used the National Heart, Lung, and Blood Institute Study Quality Assessment Tool to assess the quality of select studies.

Results Thirty-three publications met inclusion criteria. Most studies support the association between bereavement and maladaptive changes in immune parameters in adults, with mixed findings on bereavement-related changes in cellular immunity. A handful of recent, good-quality studies show bereaved people demonstrate higher levels of systemic inflammation, maladaptive immune cell gene expression, and lower antibody response to vaccination compared with nonbereaved controls. Individual differences in psychological response to bereavement (e.g., depression, grief) seem to influence the association between bereavement and immune function.

Conclusions Research examining the association between bereavement and biomarkers of immune function is heterogeneous in methods and quality. Despite these limitations, there is evidence supporting maladaptive changes in immune function after bereavement. The research area would benefit from longitudinal research with larger sample sizes, advanced immunological methods, and incorporating measures of psychological responses to bereavement. The field is poised to refine and scale up its investigation of this common and important phenomenon.

From the Department of Psychology (Knowles, Ruiz, O'Connor), University of Arizona, Tucson.

Address correspondence to Lindsey M. Knowles, MA, Department of Psychology, University of Arizona, 1503 E University Blvd, P.O. Box 210068, Tucson, AZ 85721. E-mail:

Supplemental Content

Received for publication February 22, 2018; revision received February 6, 2019.

Online date: April 4, 2019

Copyright © 2019 by American Psychosomatic Society
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