Elsevier

Psychoneuroendocrinology

Volume 100, February 2019, Pages 190-197
Psychoneuroendocrinology

Grief, depressive symptoms, and inflammation in the spousally bereaved

https://doi.org/10.1016/j.psyneuen.2018.10.006Get rights and content

Highlights

  • Inflammatory markers can distinguish bereaved spouses higher on grief severity compared with bereaved spouses with lower grief severity.

  • Even in a population high on depressive symptoms, there is a positive relationship between depression and inflammation.

  • Similar to the general population, inflammation is an important marker of elevated levels of depression among bereaved spouses.

Abstract

Grief is conceptualized by strong negative emotions, which include longing, sadness, and preoccupations with thoughts, recollections, and images of the spouse. In the initial months after the loss of a spouse, those who are widowed are at risk for cardiovascular problems and premature mortality. In the general population, depression is characterized by chronic low-grade inflammation, a key predictor of cardiovascular problems, morbidity, and mortality. Although depression and grief share similarities, they are distinct constructs. We aimed to identify if grief was related to inflammation among those who had a spouse recently die. We also sought to determine if those who are widowed and already experience elevated levels of depressive symptoms compared with the general population had higher levels of inflammation compared with those who are widowed who report fewer depressive symptoms. Ninety-nine recently bereaved individuals (M = 84.74 days since passing, SD = 18.17) completed a blood draw and psychological assessments. Proinflammatory T cell-derived cytokines were assessed, which included interferon gamma (IFN-γ), interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL17-A, and IL-2. Bereaved individuals with a higher grief severity (using an established cut-score) had higher levels of the proinflammatory cytokines IFN-γ, IL-6, and TNF-α than those with less grief severity. Those who experienced higher levels of depression exhibited elevated levels of proinflammatory cytokines compared with those who had lower levels of depression (using a continuous measure of depressive symptoms, as well as an established cut score). This is the first study to demonstrate that inflammatory markers can distinguish those who are widowed based on grief severity such that those who are higher on grief severity have higher levels of inflammation compared with those who are lower on grief severity. These findings also add to the broader literature on depression and inflammation by showing that even in a population with high levels of depressive symptoms, there is a positive relationship between depression and inflammation.

Introduction

The loss of a spouse is an extremely stressful life event that puts people at risk for mental and physical health problems (Stahl et al., 2016). Bereavement is linked with an increased risk of cardiovascular disease (CVD), and premature mortality (Moon et al., 2013). Even after adjusting for established risk factors, the death of a spouse is associated with an increased rate of mortality from cardiovascular events (Hart et al., 2007). The first 3 months after the loss of a spouse puts people at the greatest risk for cardiovascular events (Shor et al., 2012). In a matched cohort study using a primary care database, sixteen percent of the bereaved group experienced a myocardial infarction (MI) or a stroke within 30 days after the loss compared with 0.08% of the non-bereaved controls during the same period (Carey et al., 2014). This association existed separately for MI, pulmonary embolisms, and acute coronary syndrome. Furthermore, at 90 days after the loss, bereaved individuals were still at considerable risk for non-MI acute coronary syndrome and a pulmonary embolism compared with non-bereaved comparisons (Carey et al., 2014).

Stressful life events, and the negative emotions they generate, can enhance inflammation through several neuroendocrine and autonomic nervous system pathways (Slavich and Irwin, 2014). Grief is conceptualized by strong negative emotions, which include shock and even denial that one’s spouse is gone (Shear, 2015). Grief consists of intense separation distress, longing, and sadness. It is common for those who are grieving to become preoccupied with thoughts, recollections, and images of the spouse (Shear, 2015). Grief is also focused on excessive avoidance of reminders of the loss (Shear, 2015). We do not know if grief severity is associated with elevated levels of inflammation.

Higher grief severity is associated with elevated levels of depressive symptoms; however, depression and grief are distinct constructs (Milic et al., 2017). Inflammation plays an important part in depression’s pathogenesis for a subcategory of depressed individuals; depression also primes or sensitizes larger cytokine responses to stress (Fagundes et al., 2013; Kiecolt-Glaser et al., 2015; Miller and Blackwell, 2006). However, the positive association between depression and inflammation has not been demonstrated in a population of bereaved adults; those who are widowed score above the clinical cut-off for depression much more often those than in the general population, especially during the first few months after the loss (Zisook and Shuchter, 1991). There is a possibility that a ceiling effect exists such that depression is already so elevated that there is no variance to detect a positive relationship between the “most depressed (those who have more depressive symptoms)” bereaved adults and bereaved adults who are “less depressed (those who have fewer depressive symptoms).”

In this study, we aimed to identify if grief was related to inflammation among those who had a spouse recently die. We also evaluated if depressive symptoms were associated with inflammation among bereaved adults. Given that bereaved individuals generally have high levels of depressive symptoms, it is unclear if there is still a gradient increase in inflammation as depressive symptoms rise in this population. Spousally bereaved individuals completed a blood draw and psychological assessments very shortly after the loss of their spouse. We hypothesized that those who had a higher degree of grief symptomology would have greater levels of inflammation, as well as more depressive symptoms, relative to those with lower grief symptoms post-loss. We also hypothesized that bereaved individuals with more depressive symptoms would have higher levels of inflammation compared with bereaved individuals with fewer depressive symptoms.

Section snippets

Study sample

Individuals who recently experienced the loss of their spouse were contacted and recruited from obituaries, support groups, flyer distribution, online postings, and community events. All recruitment strategies were approved by the local Institutional Review Board (IRB). Exclusion criteria included significant visual or auditory impairment, being pregnant or nursing (women), autoimmune and inflammatory diseases, having experienced bereavement due to loss of another loved one in the last year,

Results

First, we evaluated the association between inflammatory markers and grief using the case categorical approach. Using the composite index of each cytokine (IL-6, TNF-α, and IFN-γ, IL17-A, and IL-2), bereaved individuals who met or exceeded the grief cut-point had higher levels of the cytokine composite in the unadjusted (p =  .029; η2= 0.05) and adjusted models (p =  .035; η2= 0.05) relative to those who were below the cut-point (means are not meaningful and thus not reported because they are

Discussion

Bereaved individuals with higher grief severity, using a case categorical approach, had higher levels of proinflammatory T cell-mediated cytokine production (an important CVD risk factor) than those who did not. Those who experienced more depressive symptoms showed elevated levels of proinflammatory cytokines compared with those who had fewer depressive symptoms. Those who met the clinical cut-off for MDD also had higher levels of proinflammatory cytokine production than those who did not.

Conclusion

In conclusion, this study adds to our growing understanding of the mechanisms that underlie CVD among those who are bereaved. Specifically, it is (a) the first study to demonstrate that inflammatory markers can distinguish those with higher grief severity compared with those with lower grief severity, and (b) a relationship exists between depression and inflammation among bereaved individuals. Future longitudinal studies that examine links between grief and inflammation are an important next

Conflicts of interest

The authors have no conflicts of interest.

Acknowledgements

This work was supported by the National Heart, Lung, and Blood Institute (1R01HL127260-01). The technical assistance of Mr. Jia Liu is gratefully acknowledged. We are very grateful to Patricia Morales and Kristi Parker for project coordination. We appreciate Lani DuFresne for editing the manuscript.

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