Circulating endocannabinoid concentrations in grieving adults

Abstract

Bereavement is one of the most intense, distressing, and traumatic events an elderly person will experience. The symptom responses to bereavement vary, particularly during the first year. However, the neurobiology underlying the symptom variance in grief is poorly understood. The endocannabinoid signaling (ECS) system is stress-responsive; mounting evidence implicates the central ECS in psychopathology. The current study aimed to investigate the hypothesis that the ECS is abnormal in grief, using circulating eCB concentrations as a biomarker of central ECS. A predominantly older sample of grief participants, within 13 months following the death of a loved one, and healthy comparison (HC) participants were studied. Associations of circulating eCBs with symptom variance in grievers were also examined. A total of 61 (grief: n = 44; HC: n = 17) adults completed cross-sectional clinical assessments and a fasting blood draw. Assessments included the Inventory of Complicated Grief scale; the 17-item Hamilton Depression Rating Scale; and the Hamilton Anxiety scale. Serum eCB concentrations (i.e., N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol [2-AG]) were quantified using isotope dilution, liquid chromatography-mass spectrometry. Relative to HC participants, grievers had significantly elevated serum AEA but similar 2-AG concentrations. In grievers, serum AEA concentrations were positively associated with depressive and anxiety symptoms, but only in those with low grief symptoms. These novel findings indicate that elevated circulating eCB concentrations are found following bereavement. The eCB signaling response varies based on the degree of grief severity. Circulating eCB measures may have the potential to serve as biomarkers of prolonged grief disorder.

Keywords: Bereavement; Endocannabinoid signaling system; Endocannabinoids; Grief; Older adults; Prolonged grief disorder.

Fig. 1

Circulating endocannabinoid concentration differences between grief and healthy comparison participants. Illustration of serum (a) AEA and (b) 2-AG group differences. In the boxplot, data indicated by circles and asterisks are 1.5 and 3.0 interquartile range beyond the third quartile, respectively. Abbreviations. AEA: N-arachidonoylethanolamine or anandamide; 2-AG: 2-arachidonoylglycerol.

Fig. 2

Relationship between serum AEA concentrations and multidomain clinical variables. Illustration of age, gender, and time since bereavement adjusted (a) HAM-D, (b) HAM-A, and (c) ICG scores in grief. Fig. 2a–c show the residuals after adjusting for age, gender, and time since bereavement and the linear regression line. Abbreviations. adj: adjusted; AEA: N-arachidonoylethanolamine or anandamide; HAM-D: 17-item Hamilton Depression Rating Scale; HAM-A: 14-item Hamilton Anxiety Scale; ICG: Inventory of Complicated Grief Scale.

Fig. 3

Relationship of serum AEA concentrations with (a) depressive and (b) anxiety symptoms according to the degree of grief symptom severity. Fig. 3a,b show the residuals after adjusting for age, gender, and time since bereavement and the linear regression line for each group. The high (i.e., ICG > 30) and low (i.e., ICG < 30) grief symptom groups are depicted by solid blue and dashed red lines respectively. Participants included in the high and low grief groups are presented as filled blue diamond and open red circles respectively. Abbreviations. adj: adjusted; AEA: N-arachidonoylethanolamine or anandamide; HAM-D: 17-item Hamilton Depression Rating Scale; HAM-A: 14-item Hamilton Anxiety Scale; ICG: Inventory of Complicated Grief Scale (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).