Prolonged grief disorder (PGD) is a diagnostic entity now included in the International Classification of Diseases 11th Revision (ICD-11) and soon to appear in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text revision (DSM-5-TR). A characteristic feature of PGD is distressing, disabling yearning that persists a year or more after the loss. Other characteristic symptoms include disbelief and lack of acceptance of the loss, emotional detachment from others since the loss, loneliness, identity disturbance, and sense of meaninglessness. In this review, we detail psychiatric views on grief and their evolution over the twentieth century. We then discuss the development of diagnostic formulations for disordered grief, which culminated in PGD's status as a mental disorder in the DSM. After summarizing recent evidence that may suggest that PGD is linked to the neural reward system, we suggest further areas of research. In particular, we note the need for studies that extend the evidence base concerning PGD across cultural and sociodemographic boundaries and that investigate novel treatments. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 17 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Prolonged Grief Disorder (PGD) is a debilitating condition affecting between 7% and 10% of bereaved individuals. Past imaging and psychological studies have proposed links between PGD's characteristic symptoms -in particular, profound yearning -and the neural reward system. We conducted a systematic review to investigate this connection. On December 19, 2019, we searched six bibliographic databases for data on the neurobiology of grief and disordered grief. We excluded studies of the hypothalamic-pituitary-adrenal (HPA) axis, animal studies, and reviews. After abstract and full-text screening, twenty-four studies were included in the final review. We found diverse evidence for the activation of several reward-related regions of the brain in PGD. The data reviewed suggest that compared to normative grief, PGD involves a differential pattern of activity in the amygdala and orbitofrontal cortex (OFC); likely differential activity in the posterior cingulate cortex (PCC), rostral or subgenual anterior cingulate cortex (ACC), and basal ganglia overall, including the nucleus accumbens (NAc); and possible differential activity in the insula. It

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Background: Bereavement is associated with impaired mental health, increases in adverse health behaviors, and heightened risk of suicidal ideation, attempts, and death by suicide. The purpose of this literature review was to explore associations between cause of death and suicidal thoughts among bereaved individuals. Our aim was to compare incidence of suicidal ideation by cause of death and identify gaps in this literature to guide future research and clinical intervention. Methods: PRISMA-P guidelines were used to structure an electronic literature search in the PsycINFO, MEDLINE, and Web of Science databases. The search focused on English language studies that were published before February 2019 and sought to compare rates of suicidal ideation among bereaved people who lost a loved one to suicide, accidental overdose, cancer, dementia, cardiovascular disease, and HIV/AIDs. Results: Nine articles were identified with suicide as cause of death, zero articles for accidental overdose, zero articles for cardiovascular disease, seven articles for cancer, one article for dementia, and one article for HIV/AIDs. Given the limited number of articles generated by our search, a formal meta-analysis was not appropriate. However, a comparison of results did suggest that suicide bereavement was associated with the highest rates of suicide ideation (14.1% to 49%). Stigma, isolation, avoidance behaviors, and psychological distress were associated with suicidal thoughts among bereaved individuals, regardless of the deceased’s cause of death. Conclusions: Findings of this literature search revealed significant gaps in the literature, especially regarding thoughts of suicide in bereaved survivors of accidental overdose and cardiovascular disease. Results suggest that multiple causes of death are associated with suicidal ideation in bereavement, but that suicide bereavement may be the cause of death associated with the highest risk of suicidal ideation. More research is needed to understand the ways in which cause of death influences prevalence, risk, and protective factors associated with suicidal thoughts among bereaved individuals.

Background There is a lack of effective pharmacotherapy for prolonged grief disorder (PGD). Evidence suggests that the neurobiology of PGD involves the same circuitry as the reward pathway. Based upon this evidence, we hypothesize that PGD can be conceptualized as a disorder of addiction and therefore could benefit from being treated with medications that are currently used to treat such disorders. One such medication is naltrexone, which is currently used to treat alcohol and opioid dependence. Oral naltrexone was chosen for its mechanism of action, safety, and convenience. The primary aim of this study is to establish the efficacy of using oral naltrexone as a pharmacological treatment for PGD. Specifically, we hypothesize that participants receiving naltrexone will demonstrate reduced PGD symptoms when compared to placebo. Methods/design This is a randomized, placebo-controlled, triple-blinded (to healthcare professionals/study staff, participants, and data analysts) study in which we propose to enroll 48 participants who meet criteria for Prolonged Grief Disorder (PGD). Participants will be randomly assigned to the naltrexone 50 mg oral arm or placebo arm; medications will be over-encapsulated to appear identical. Participants will take their assigned medication for 8 weeks, with clinic visits every 4 weeks to assess symptom severity, social closeness, and adverse reactions. Weekly surveys of Prolonged Grief-13-Revised (PG-13-R) will be used to relate naltrexone use to changes in PGD symptom severity. Follow-up 4 weeks after their last visit will assess the longevity of treatment, as well as any lingering adverse reactions. Discussion This study is the first to investigate the use of oral naltrexone as pharmacological treatment for PGD. The acute and debilitating nature of the disorder, in addition to the increased risk of comorbidities, highlights the need for pharmacological treatment like naltrexone that can act more rapidly, may help those for whom psychotherapy may not be effective, and/or may augment psychotherapy to promote PGD symptom grief resolution. Trial registration ClinicalTrials.govNCT04547985. Registered on 8/31/2020.