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Background: Prolonged Grief Disorder is a multidimensional condition with adverse health consequences. We hypothesized that enhanced negative emotional bias characterizes this disorder and underlies its key clinical symptoms., Methods: In a cross-sectional design, chronically grieving older adults (61.5±8.9 years old) experiencing probable Prolonged Grief Disorder (PGD; n=33) were compared with demographic- and time since loss-equated integrated (adaptive) grief participants (n=38). To probe generalized negative affective reactivity, participants performed an emotional face-matching task during fMRI scanning, and demographic and clinical assessments. Contrast maps (fearful + angry faces (-) shapes) were generated to determine group differences in brain activity within hypothesized affective and regulatory processing regions (amygdala, anterior insula, dorsal anterior cingulate, dorsolateral prefrontal cortex) and in exploratory whole-brain regression analyses., Results: The PGD group showed higher right amygdala activation to negative emotional stimuli, compared to the integrated grief group (p corr <0.05), which positively correlated with intrusive thoughts. Generalized psychophysiological interaction analysis revealed lower task-dependent functional connectivity between the right amygdala and posterior cingulate cortex/precuneus in PGD (p corr <0.05), which negatively correlated with avoidance of loss reminders. Resting-state functional connectivity between the identified right amygdala and thalamus was higher in PGD (p corr <0.05), which negatively correlated with loneliness., Conclusions: Dysregulated amygdala-centric neural activity and functional connectivity during processing of negative affective stimuli and at rest appear to differentiate prolonged from integrated grief in older adults. Future investigations using interventions to target amygdala-centric neural circuit abnormalities may provide new insights into the role of enhanced negative bias and related mechanisms underlying PGD and support treatment efficacy., (Copyright © 2024. Published by Elsevier Inc.)

Prolonged grief disorder (PGD) is associated with impairments in cognitive functioning, but the neuropsychological correlates of early grief in older adults are poorly understood. This preliminary study cross-sectionally examined neuropsychological functioning in bereaved adults with high and low grief symptoms and a non-bereaved comparison sample and further explored the relationship between multidomain cognitive measures and grief severity. A total of ninety-three nondemented older adults (high grief: n = 44; low grief: n = 49) within 12 months post-bereavement and non-bereaved comparison participants ( n = 43) completed neuropsychological battery including global and multiple domain-specific cognitive functioning. Linear regression models were used to analyze differences in multidomain cognitive measures between the groups and specifically examine the associations between cognitive performance and grief severity in the bereaved, after covariate adjustment, including depressive symptoms. Bereaved older adults with higher grief symptoms performed worse than those with lower symptoms and non-bereaved participants on executive functioning and attention and processing speed measures. In the bereaved, poorer executive functioning, attention and processing speed correlated with higher grief severity. Attention/processing speed-grief severity correlation was seen in those with time since loss ≤ 6 months, but not > 6 months. Intense early grief is characterised by poorer executive functioning, attention, and processing speed, resembling findings in PGD. The putative role of poorer cognitive functioning during early grief on the transition to integrated grief or the development of PGD remains to be elucidated.

Bereaved older adults experiencing high grief in the first year after an attachment loss is at increased risk for prolonged grief disorder (PGD) via unknown mechanisms. Yearning, a core grief symptom, is linked to the ventral striatal (VS) brain function, but the role of this neuronal system in late-life grief is poorly understood. As a first step, we examined the VS subregional abnormalities associated with multidimensional symptoms in bereaved elders during the first year post-loss. Sixty-five bereaved elders completed clinical assessments within 13 months post-loss. Ventral caudate (VCau) and nucleus accumbens (NAcc) functional connectivity (FC) was assessed using seed-based resting-state functional MRI. VCau and NAcc FC differences between high (inventory of complicated grief [ICG] score≥30; n = 35) and low (ICG score<30; n = 30) grief, and the relationships between ventral striatal subregional FC and clinical measures (yearning and depressive symptoms) were assessed after covariate adjustments (α < 0.05; 3dClustSim corrected). Relative to low grief participants, those with high grief showed higher FC between VCau and the medial prefrontal, orbitofrontal, and subgenual cingulate cortices. VCau FC abnormalities positively correlated with yearning (r 2  = 0.24, p < 0.001). In contrast, FC between VCau and temporoparietal junction negatively correlated with depressive symptoms, a commonly co-occurring symptom (r 2  = 0.37, p < 0.001). The FC between NAcc and insula/striatum positively correlated with yearning (r 2  = 0.35, p < 0.001); no other NAcc FC findings were seen in the full sample. In women, higher FC between the NAcc and bilateral posterior cingulate, precuneus, and visual areas were found in those with high, relative to low grief symptoms. Distinct VS subregional abnormalities associate with yearning and depressive symptoms in bereaved elders. Whether ventral striatal dysfunction correlates with PGD development and/or worsening depression remains to be elucidated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Loneliness is one of the most distressing grief symptoms and is associated with adverse mental health in bereaved older adults. The endocannabinoid signaling (ECS) system is stress-responsive and circulating endocannabinoid (eCB) concentrations are elevated following bereavement. This study examined the association between loneliness and circulating eCB concentrations in grieving older adults and explored the role of eCBs on the association between baseline loneliness and grief symptom trajectories. Methods: A total of 64 adults [grief with high loneliness: n = 18; grief with low loneliness: n = 26; and healthy comparison (HC): n = 20] completed baseline clinical assessments for the UCLA loneliness scale. In grief participants, longitudinal clinical assessments, including the Inventory of Complicated Grief and 17-item Hamilton Depression Rating scales, were collected over 6 months. Baseline circulating eCB [ N -arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG)] concentrations were quantified in the serum using isotope dilution, liquid chromatography-mass spectrometry; cortisol concentrations were measured in the same samples using radioimmunoassay. Results: Circulating AEA concentrations were higher in severely lonely grieving elders than in HC group; cortisol concentrations were not different among the groups. Cross-sectionally, loneliness scores were positively associated with AEA concentrations in grievers; this finding was not significant after accounting for depressive symptom severity. Grieving individuals who endorsed high loneliness and had higher 2-AG concentrations at baseline showed faster grief symptom resolution. Conclusions: These novel findings suggest that in lonely, bereaved elders, increased circulating eCBs, a reflection of an efficient ECS system, are associated with better adaptation to bereavement. Circulating eCBs as potential moderators and mediators of the loneliness-grief trajectory associations should be investigated., Competing Interests: CH has equity and is on the Scientific Advisory Board for Formulate Biosciences and is on the Scientific Advisory Board for Phytecs, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kang, Bohorquez-Montoya, McAuliffe, Claesges, Blair, Sauber, Reynolds, Hillard and Goveas.)

Loneliness is associated with adverse mental health outcomes in older adults. Bereavement triggers intense feelings of loneliness. This pilot study explored the association between baseline loneliness and grief symptom trajectories in bereaved elders and explored if this association is moderated by depressive symptom changes. 56 individuals aged 50 years and older, within 13-months following bereavement, completed assessments. Loneliness was measured at baseline using the UCLA loneliness scale-version 3. Grief and depressive symptoms were measured over 26 weeks using the inventory of complicated grief (ICG) and the 17-item Hamilton Depressive Rating (HAM-D) scales, respectively. Linear regression explored the cross-sectional association between loneliness and grief symptoms, after adjusting for covariates including depressive symptoms. A mixed-effects linear model tested whether baseline loneliness was related to grief symptom trajectory over 26 weeks, after accounting for depressive symptom changes. Loneliness was associated with grief symptom severity at baseline; however, this cross-sectional association was not significant after adjusting for depressive symptoms. Longitudinally, baseline loneliness was positively associated with grief symptom trajectories; however, depressive symptom changes moderated this association. Depressive symptom alterations appear to weaken the loneliness-grief symptom change association. These exploratory findings point to opportunities for interventions targeting loneliness and depression that may reduce grief intensity over time in bereaved elders., Competing Interests: Declarations of interest: None Conflicts of Interest: Cecilia J Hillard is on the Scientific Advisory Boards of Phytecs, Inc and Formulate Biosciences and has equity in Formulate Biosciences. These companies are developing cannabis-based drugs. Other authors have no conflicts of interest to report.

Objective: Acute grief, in an important minority of older adults, can become protracted, intense, and debilitating, leading to the development of complicated grief (CG). However, the neurobiologic mechanisms underlying a maladaptive grief response after an attachment loss are unknown. The current study aimed to examine the amygdala brain network features that cross-sectionally explain the symptom variance and longitudinally relate to grief symptom trajectories after an attachment loss., Methods: Baseline amygdala functional connectivity (Fc) was assessed using a seed-based resting-state functional magnetic resonance imaging method in 35 adults who were within 1-year after death of a loved one and 21 healthy comparison (HC) participants. Magnetic resonance imaging scans were obtained at baseline, and clinical assessments, including the inventory of complicated grief (ICG) were completed at weeks 0, 8, 16, and 26 (endpoint)., Results: Relative to HC participants, grief participants showed increased amygdala Fc in the posterior default mode (bilateral medial temporal lobes and left precuneus) and thalamus. Amygdala Fc in the default mode and ventral affective regions positively correlated with ICG scores at baseline. Furthermore, increased baseline amygdala functional connections with the dorsal frontal executive control and salience network regions correlated with worsening ICG scores over time. These longitudinal findings persisted after controlling for covariates, including baseline depressive and anxiety symptoms., Conclusion: These results provide novel preliminary evidence suggesting amygdala-based brain network measures to cross-sectionally explain symptom variance and longitudinally correlate with grief symptom trajectories in grievers. Amygdala brain network function measures may have the potential to serve as biomarkers of CG., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)