Biological markers of grief in bereaved family members: A systematic review of cortisol, inflammatory and cardiovascular studies.

Bereavement is among life's most stressful events, and a minority of mourners develop prolonged and disabling grief. Biological markers have been proposed as signals of this risk, but no systematic review has examined them across bereaved family members or asked how well bereaved parents (parents who have lost a child) are represented. We systematically reviewed observational studies linking a cortisol/HPA-axis, inflammatory/immune, or cardiovascular/autonomic biomarker to a validated measure of coping or grief in bereaved family members of any age or relationship to the deceased (PROSPERO CRD420261446539). Five databases were searched, with citation searching of a related review. Eighteen studies met inclusion criteria across the three domains. More severe grief was linked to blunted or flatter diurnal cortisol in three of five cortisol studies. Bereavement and greater grief were linked to raised inflammatory markers (IL-6, IL-1RA, and related cytokines), although five of seven inflammatory studies appear to come from one research programme, and one study found divergent Type I interferon gene transcription in complicated relative to uncomplicated grief. Cardiovascular and autonomic findings were mixed and depended on moderators such as coping style and childhood adversity. Some cortisol associations weakened with time since loss, so they may not be stable markers of grief severity. Only one participant across all 18 studies was an identifiable bereaved parent. Biological markers show domain-specific associations with grief, but the evidence is exploratory, and bereaved parents are largely absent from it. They should be a priority for future prospective work.