Neuroendocrine mechanisms of grief and bereavement: A systematic review and implications for future interventions

Abstract

Bereavement is associated with many negative behavioural, psychological and physiological consequences and leads to an increased risk of mortality and morbidity. However, studies specifically examining neuroendocrine mechanisms of grief and bereavement have yet to be reviewed. This systematic review is a synthesis of the latest evidence in this field and aims to draw conclusions about the implications of neurobiological findings on the development of new interventions. PRISMA guidelines for systematic reviews were used to search for articles assessing neuroendocrine correlates of grief. Findings were qualitatively summarised. The National Heart, Lung, and Blood Institute Study Assessment Tool was used to assess the quality of the included studies. Out of 460 papers, 20 met the inclusion criteria. However, most were of fair quality only. As a neuroendocrine marker, the majority of the studies reported cortisol as the outcome measure and found elevated mean cortisol levels, flattened diurnal cortisol slopes and higher morning cortisol in bereaved subjects. Cortisol alterations were moderated by individual differences such as emotional reaction to grief, depressive symptoms, grief severity, closeness to the deceased and age or gender. Research on neuroendocrine mechanisms of grief is still in its early stages regarding grief measures and the use and timing of neuroendocrine assessments. Most of the studies focus on cortisol as outcome, and only limited data exist on other biomarkers such as oxytocin. Future research might consider assessing a broader range of neuroendocrine markers and use longitudinal designs with a focus on the psychobiological reactions to loss. Based on this, individually tailored psychosocial interventions, possibly in the palliative care context, might be developed to prevent prolonged grief disorder.

The brain oxytocin and corticotropin-releasing factor systems in grieving mothers: What we know and what we need to learn

“…Furthermore, morning and daytime cortisol levels were higher in participants with PGD than in normal grieving or non-grieving participants, the latter two being no different from each other [178]. In a recent review, it emerged that the loss of a loved one can be associated with neuroendocrine alterations both in the early / acute stage and in the late / chronic stage of bereavement [27]. In general, people with PGD have flattened daytime cortisol curves and reduced morning cortisol levels when compared to people in normal bereavement.…”

“…The neurobiology of grief is an emerging research field that is constantly growing but unfortunately, scientific research has been influenced by a strong sex J o u r n a l P r e -p r o o f bias that has created a lack of knowledge of female physiology [22], thereby also leading to the little we know about grieving mothers' neurophysiology and emotionality. Hence, we aim to review the current literature on the neurobiological impact of losing a child on the mother with focus on neuropeptide systems known to facilitate (oxytocin; OXT) or to hinder (corticotropin-releasing factor; CRF) adequate mothering ( [23]; [24]; [25]; [26]) (for a more general review of neuroendocrine mechanisms in grief and bereavement see [27]). Given the severe paucity of scientific research in this field, we decided to include examples of relevant studies on repeated forced mother-offspring separation.…”

Interactions between theκopioid system, corticotropin-releasing hormone and oxytocin in partner loss

“…elevated KORs in the NAcc that respond to separation from the partner. Prairie voles may also demonstrate a higher sensitivity to manipulation of the κ opioid system than rats or mice, with higher levels of KOR agonist-stimulated [ 35 S]GTPγS binding in forebrain areas-which could also be theoretically related to the capacity for demonstrating separation distress [98]. For additional reading on OT and opioid interactions in the context of their relation to pair-bond formation in prairie voles, we recommend the recent review [99].…”

“…In humans, the cingulate cortex [ 29 ] and nucleus accumbens (NAcc) [ 30 ], as well as the amygdala [ 31 ] and insula [ 32 , 33 ], have been implicated in bereavement in functional magnetic resonance imaging studies [ 34 ]. The vast majority of studies on the endocrine correlates of prolonged grief in humans have focused on cortisol and the HPA axis, with substantial evidence that grief is associated with higher cortisol levels [ 35 ]. In humans, relationship distress is often associated with elevated plasma OT [ 36 ], particularly in women [ 37 , 38 ], and specifically in prolonged grief [ 36 ].…”

Loneliness and diurnal cortisol levels during COVID-19 lockdown: the roles of living situation, relationship status and relationship quality

“…Divorced and widowed individuals show significantly higher loneliness scores than married individuals 44-46 . Furthermore, partner loss is accompanied by altered HPA axis functioning, resulting in elevated cortisol levels and flattened diurnal cortisol slopes 47 .…”