Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Prolonged grief disorder in later life: advancing our understanding of biopsychosocial mechanisms to guide future personalized interventions

Neuropsychopharmacology (2026)Cite this article

Subjects

Abstract

Grief is a near-universal yet profoundly traumatic human experience, symbolizing a testament to the depth of our emotional bonds while reminding us of life’s fragility. Although most individuals adapt to loss over time, 3-10% develop Prolonged Grief Disorder (PGD), a chronic and debilitating condition recognized in both the DSM-5-TR and ICD-11. Older adults are particularly vulnerable: PGD in later life poses significant public health risks, including adverse physical health outcomes, cognitive decline, and increased premature mortality, underscoring the urgent need for early identification and effective interventions in this population. This narrative review examines psychological, social, and neurobiological perspectives on grief, highlighting distinctions between acute, integrated, and PGD trajectories. We trace the evolution of PGD as a diagnostic entity and review its risk factors, clinical presentation, comorbidities, assessment, and current treatment approaches. We then propose a neurobiological model of late-life PGD, grounded in cognitive neuroscience and emphasizing the roles of key intrinsic brain networks: the Salience Network, Default Mode Network, and Executive Control Network. Finally, we outline future directions for the field, calling for neuroimaging studies that integrate biological markers with psychosocial factors to refine diagnosis and inform targeted interventions. This review advocates for a biopsychosocial framework to advance understanding and treatment of PGD in older adults.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Theoretical framework.
Fig. 2: Hypothesized Functional Neuroanatomy of Late-Life Prolonged Grief Disorder.
Fig. 3: Biopsychosocial Working Model of Late-Life Prolonged Grief Disorder.

Similar content being viewed by others

References

  1. Prigerson HG, Shear MK, Reynolds CF 3rd. Prolonged grief disorder diagnostic criteria-helping those with maladaptive grief responses. JAMA Psychiatry. 2022;79:277–78.

    Article  PubMed  Google Scholar 

  2. Simon NM, Shear MK. Prolonged grief disorder. N Engl J Med. 2024;391:1227–36.

    Article  PubMed  Google Scholar 

  3. Prigerson HG, Boelen PA, Xu JH, Smith KV, Maciejewski PK. Validation of the new DSM-5-TR criteria for prolonged grief disorder and the PG-13-Revised (PG-13-R) scale. World Psychiatry. 2021;20:96–106.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Prigerson HG, Bierhals AJ, Kasl SV, Reynolds CF 3rd, Shear MK, Day N, et al. Traumatic grief as a risk factor for mental and physical morbidity. Am J Psychiatry. 1997;154:616–23.

  5. Szanto K, Prigerson H, Houck P, Ehrenpreis L, Reynolds CF 3rd. Suicidal ideation in elderly bereaved: the role of complicated grief. Suicide Life Threat Behav. 1997;27:194–207.

    Article  CAS  PubMed  Google Scholar 

  6. Latham AE, Prigerson HG. Suicidality and bereavement: complicated grief as psychiatric disorder presenting greatest risk for suicidality. Suicide Life Threat Behav. 2004;34:350–62.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Szanto K, Shear MK, Houck PR, Reynolds CF 3rd, Frank E, Caroff K, Silowash R. Indirect self-destructive behavior and overt suicidality in patients with complicated grief. J Clin Psychiatry. 2006;67:233–9.

    Article  PubMed  Google Scholar 

  8. Stroebe M, Schut H, Stroebe W. Health outcomes of bereavement. Lancet. 2007;370:1960–73.

    Article  PubMed  Google Scholar 

  9. Perez HCS, Ikram MA, Direk N, Tiemeier H. Prolonged grief and cognitive decline: a prospective population-based study in middle-aged and older persons. Am J Geriatr Psychiatry. 2018;26:451–60.

    Article  PubMed  Google Scholar 

  10. Kaprio J, Koskenvuo M, Rita H. Mortality after bereavement: a prospective study of 95,647 widowed persons. Am J Public Health. 1987;77:283–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen JH, Bierhals AJ, Prigerson HG, Kasl SV, Mazure CM, Jacobs S. Gender differences in the effects of bereavement-related psychological distress in health outcomes. Psychol Med. 1999;29:367–80.

    Article  CAS  PubMed  Google Scholar 

  12. Shear MK, Simon N, Wall M, Zisook S, Neimeyer R, Duan N, et al. Complicated grief and related bereavement issues for DSM-5. Depress Anxiety. 2011;28:103–17.

    Article  PubMed  Google Scholar 

  13. Prigerson HG, Bridge J, Maciejewski PK, Beery LC, Rosenheck RA, Jacobs SC, et al. Influence of traumatic grief on suicidal ideation among young adults. Am J Psychiatry. 1999;156:1994–5.

    Article  CAS  PubMed  Google Scholar 

  14. Holland JM, Graves S, Klingspon KL, Rozalski V. Prolonged grief symptoms related to loss of physical functioning: examining unique associations with medical service utilization. Disabil Rehabil. 2016;38:205–10.

    Article  PubMed  Google Scholar 

  15. Simon NM, Pollack MH, Fischmann D, Perlman CA, Muriel AC, Moore CW, et al. Complicated grief and its correlates in patients with bipolar disorder. J Clin Psychiatry. 2005;66:1105–10.

    Article  PubMed  Google Scholar 

  16. Sung SC, Dryman MT, Marks E, Shear MK, Ghesquiere A, Fava M, et al. Complicated grief among individuals with major depression: prevalence, comorbidity, and associated features. J Affect Disord. 2011;134:453–8.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Parisi A, Sharma A, Howard MO, Blank Wilson A. The relationship between substance misuse and complicated grief: a systematic review. J Subst Abus Treat. 2019;103:43–57.

    Article  Google Scholar 

  18. Freud S. Mourning and Melancholia. The Standard edition of the complete psychological works of sigmund freud, volume XIV (1914-1916): on the history of the psycho-analytic movement, papers on metapsychology and other works. London: The Hogarth Press and the Institute of Psycho-analysis; 1917. p. 237–58.

  19. Lindemann E. Symptomatology and management of acute grief. Am J Psychiatry. 1944;101:141–48.

    Article  Google Scholar 

  20. Bowlby J. Attachment and loss. Loss, sadness and depression. New York, NY: Basic Books; 1980.

  21. Bowlby J. Processes of mourning. Int J Psychoanal. 1961;42:317–40.

    CAS  PubMed  Google Scholar 

  22. Bowlby J. Pathological mourning and childhood mourning. J Am Psychoanal Assoc. 1963;11:500–41.

    Article  CAS  PubMed  Google Scholar 

  23. Kubler-Ross E. On death and dying. New York: Macmillan; 1969.

  24. Worden JW. Grief counseling and grief therapy: a handbook for the mental health practitioner 5th ed. Springer: New York; 2018.

  25. Stroebe M, Schut H. The dual process model of coping with bereavement: a decade on. Omega. 2010;61:273–89.

    Article  PubMed  Google Scholar 

  26. Lazarus RS, Folkman S Stress, appraisal, and coping. New York: Springer; 1984.

  27. Stroebe M, Schut H. The dual process model of coping with bereavement: rationale and description. Death Stud. 1999;23:197–224.

    Article  CAS  PubMed  Google Scholar 

  28. Wortman CB, Silver RC. The myths of coping with loss. J Consult Clin Psychol. 1989;57:349–57.

    Article  CAS  PubMed  Google Scholar 

  29. Bonanno GA, Wortman CB, Lehman DR, Tweed RG, Haring M, Sonnega J, et al. Resilience to loss and chronic grief: a prospective study from preloss to 18-months postloss. J Pers Soc Psychol. 2002;83:1150–64.

    Article  PubMed  Google Scholar 

  30. Boerner K, Wortman CB, Bonanno GA. Resilient or at risk? A 4-year study of older adults who initially showed high or low distress following conjugal loss. J Gerontol B Psychol Sci Soc Sci. 2005;60:P67–73.

    Article  PubMed  Google Scholar 

  31. Maccallum F, Galatzer-Levy IR, Bonanno GA. Trajectories of depression following spousal and child bereavement: a comparison of the heterogeneity in outcomes. J Psychiatr Res. 2015;69:72–9.

    Article  PubMed  Google Scholar 

  32. Bonanno GA, Malgaroli M. Trajectories of grief: comparing symptoms from the DSM-5 and ICD-11 diagnoses. Depress Anxiety. 2020;37:17–25.

    Article  PubMed  Google Scholar 

  33. Bonanno GA, Kaltman S. Toward an integrative perspective on bereavement. Psychol Bull. 1999;125:760–76.

    Article  CAS  PubMed  Google Scholar 

  34. Bonanno GA, Kaltman S. The varieties of grief experience. Clin Psychol Rev. 2001;21:705–34.

    Article  CAS  PubMed  Google Scholar 

  35. Bonanno GA. Loss, trauma, and human resilience: Have we underestimated the human capacity to thrive after extremely aversive events?. Am Psychol. 2004;59:20–8.

    Article  PubMed  Google Scholar 

  36. Bonanno GA, Keltner D, Holen A, Horowitz MJ. When avoiding unpleasant emotions might not be such a bad thing: verbal-autonomic response dissociation and midlife conjugal bereavement. J Pers Soc Psychol. 1995;69:975–89.

    Article  CAS  PubMed  Google Scholar 

  37. Bonanno GA, Keltner D. Facial expressions of emotion and the course of conjugal bereavement. J Abnorm Psychol. 1997;106:126–37.

    Article  CAS  PubMed  Google Scholar 

  38. Bonanno GA, Grief and emotion: A social–functional perspective. In Handbook of bereavement research: consequences, coping, and care. Stroebe MS, Hansson RO, Stroebe W, Schut H, editors. American Psychological Association; 2001. pp. 493–515.

  39. Stroebe M, Boelen PA, van den Hout M, Stroebe W, Salemink E, van den Bout J. Ruminative coping as avoidance: a reinterpretation of its function in adjustment to bereavement. Eur Arch Psychiatry Clin Neurosci. 2007;257:462–72.

    Article  PubMed  Google Scholar 

  40. Maccallum F, Bryant RA. A cognitive attachment model of prolonged grief: integrating attachments, memory, and identity. Clin Psychol Rev. 2013;33:713–27.

    Article  PubMed  Google Scholar 

  41. Shear K, Shair H. Attachment, loss, and complicated grief. Dev Psychobiol. 2005;47:253–67.

    Article  PubMed  Google Scholar 

  42. Boelen PA, van den Bout J, van den Hout MA. Negative cognitions and avoidance in emotional problems after bereavement: a prospective study. Behav Res Ther. 2006;44:1657–72.

    Article  PubMed  Google Scholar 

  43. O’Connor MF, Seeley SH. Grieving as a form of learning: Insights from neuroscience applied to grief and loss. Curr Opin Psychol. 2022;43:317–22.

    Article  PubMed  Google Scholar 

  44. Shear K, Frank E, Houck PR, Reynolds CF 3rd. Treatment of complicated grief: a randomized controlled trial. JAMA. 2005;293:2601–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Shear MK, Wang Y, Skritskaya N, Duan N, Mauro C, Ghesquiere A. Treatment of complicated grief in elderly persons: a randomized clinical trial. JAMA Psychiatry. 2014;71:1287–95.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Shear MK, Reynolds CF 3rd, Simon NM, Zisook S, Wang Y,Mauro C, et al. Optimizing treatment of complicated grief: a randomized clinical trial. JAMA Psychiatry. 2016;73:685–94.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Horowitz MJ, Bonanno GA, Holen A. Pathological grief: diagnosis and explanation. Psychosom Med. 1993;55:260–73.

    Article  CAS  PubMed  Google Scholar 

  48. Horowitz MJ, Siegel B, Holen A, Bonanno GA, Milbrath C, Stinson CH. Diagnostic criteria for complicated grief disorder. Am J Psychiatry. 1997;154:904–10.

    Article  CAS  PubMed  Google Scholar 

  49. Prigerson HG, Frank E, Kasl SV, Reynolds CF 3rd, Anderson B, Zubenko GS, et al. Complicated grief and bereavement-related depression as distinct disorders: preliminary empirical validation in elderly bereaved spouses. Am J Psychiatry. 1995;152:22–30.

    Article  CAS  PubMed  Google Scholar 

  50. Prigerson HG, Maciejewski PK, Reynolds CF 3rd, Bierhals AJ, Newsom JT, Fasiczka A, et al. Inventory of complicated grief: a scale to measure maladaptive symptoms of loss. Psychiatry Res. 1995;59:65–79.

    Article  CAS  PubMed  Google Scholar 

  51. Prigerson HG, Shear MK, Jacobs SC, Reynolds CF 3rd, Maciejewski PK, Davidson JR, et al. Consensus criteria for traumatic grief. A preliminary empirical test. Br J Psychiatry J Ment Sci. 1999;174:67–73.

    Article  CAS  Google Scholar 

  52. Prigerson HG, Horowitz MJ, Jacobs SC, Parkes CM, Aslan M, Goodkin K, et al. Prolonged grief disorder: Psychometric validation of criteria proposed for DSM-V and ICD-11. PLoS Med. 2009;6:e1000121.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Cozza SJ, Fisher JE, Mauro C, Zhou J, Ortiz CD, Skritskaya N, et al. Performance of DSM-5 persistent complex bereavement disorder criteria in a community sample of bereaved military family members. Am J Psychiatry. 2016;173:919–29.

    Article  PubMed  Google Scholar 

  54. Maciejewski PK, Maercker A, Boelen PA, Prigerson HG. Prolonged grief disorder” and “persistent complex bereavement disorder”, but not “complicated grief”, are one and the same diagnostic entity: an analysis of data from the Yale Bereavement Study. World Psychiatry. 2016;15:266–75.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Maciejewski PK, Prigerson HG. Prolonged, but not complicated, grief is a mental disorder. Br J Psychiatry J Ment Sci. 2017;211:189–91.

    Article  Google Scholar 

  56. Boelen PA, van den Bout J. Complicated grief, depression, and anxiety as distinct postloss syndromes: a confirmatory factor analysis study. Am J Psychiatry. 2005;162:2175–7.

    Article  PubMed  Google Scholar 

  57. Langner R, Maercker A. Complicated grief as a stress response disorder: evaluating diagnostic criteria in a German sample. J Psychosom Res. 2005;58:235–42.

    Article  PubMed  Google Scholar 

  58. Boelen PA, de Keijser J, van den Hout MA, van den Bout J. Treatment of complicated grief: a comparison between cognitive-behavioral therapy and supportive counseling. J Consult Clin Psychol. 2007;75:277–84.

    Article  PubMed  Google Scholar 

  59. Boelen PA, Prigerson HG. The influence of symptoms of prolonged grief disorder, depression, and anxiety on quality of life among bereaved adults: a prospective study. Eur Arch Psychiatry Clin Neurosci. 2007;257:444–52.

    Article  PubMed  Google Scholar 

  60. Boelen PA, Van Den Bout J. Examination of proposed criteria for complicated grief in people confronted with violent or non-violent loss. Death Stud. 2007;31:155–64.

    Article  PubMed  Google Scholar 

  61. Boelen PA, van de Schoot R, van den Hout MA, de Keijser J, van den Bout J. Prolonged Grief Disorder, depression, and posttraumatic stress disorder are distinguishable syndromes. J Affect Disord. 2010;125:374–8.

    Article  PubMed  Google Scholar 

  62. Killikelly C, Maercker A. Prolonged grief disorder for ICD-11: the primacy of clinical utility and international applicability. Eur J Psychotraumatol. 2017;8:1476441.

    Article  PubMed  Google Scholar 

  63. Cacciatore J, Francis A. DSM-5-TR turns normal grief into a mental disorder. Lancet Psychiatry. 2022;9:e32.

    Article  PubMed  Google Scholar 

  64. Eisma MC. Prolonged grief disorder in ICD-11 and DSM-5-TR: challenges and controversies. Aust N Z J Psychiatry. 2023;57:944–51.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Prigerson HG, Singer J, Killikelly C. Prolonged Grief disorder: addressing misconceptions with evidence. Am J Geriatr Psychiatry. 2024;32:527–34.

    Article  PubMed  Google Scholar 

  66. Shear MK. Getting straight about grief. Depress Anxiety. 2012;29:461–4.

    Article  PubMed  Google Scholar 

  67. Shear MK, Muldberg S, Periyakoil V. Supporting patients who are bereaved. BMJ. 2017;358:j2854.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Zisook S, Simon NM, Reynolds CF 3rd, Pies R, Lebowitz B, Young IT, et al. Bereavement, complicated grief, and DSM, part 2: complicated grief. J Clin Psychiatry. 2010;71:1097–8.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Shear MK. Grief and mourning gone awry: pathway and course of complicated grief. Dialogues Clin Neurosci. 2012;14:119–28.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Antonucci TC, Akiyama H, Takahashi K. Attachment and close relationships across the life span. Attach Hum Dev. 2004;6:353–70.

    Article  PubMed  Google Scholar 

  71. Verdery AM, Smith-Greenaway E, Margolis R, Daw J. Tracking the reach of COVID-19 kin loss with a bereavement multiplier applied to the United States. Proc Natl Acad Sci USA. 2020;117:17695–701.

    Article  PubMed  PubMed Central  Google Scholar 

  72. 2024 Older Americans Key Indicators of Well-being: Federal Interagency Forum on Aging-Related Statistics. https://agingstats.gov/docs/LatestReport/Older-Americans-2024-508-May-update.pdf. Accessed June 1 2025.

  73. Lenferink LI, Nickerson A, de Keijser J, Smid GE, Boelen PA. Trajectories of grief, depression, and posttraumatic stress in disaster-bereaved people. Depression anxiety. 2020;37:35–44.

    Article  PubMed  Google Scholar 

  74. Onrust SA, Cuijpers P. Mood and anxiety disorders in widowhood: a systematic review. Aging Ment Health. 2006;10:327–34.

    Article  CAS  PubMed  Google Scholar 

  75. Keyes KM, Pratt C, Galea S, McLaughlin KA, Koenen KC, Shear MK. The burden of loss: unexpected death of a loved one and psychiatric disorders across the life course in a national study. Am J Psychiatry. 2014;171:864–71.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Zisook S, Shuchter SR. Depression through the first year after the death of a spouse. Am J Psychiatry. 1991;148:1346–52.

    Article  CAS  PubMed  Google Scholar 

  77. Clayton PJ, Halikas JA, Maurice WL. The depression of widowhood. Br J Psychiatry J Ment Sci. 1972;120:71–7.

    Article  CAS  Google Scholar 

  78. Clayton PJ. Bereavement and depression. J Clin Psychiatry. 1990;51:34–8.

    PubMed  Google Scholar 

  79. Clayton P, Desmarais L, Winokur G. A study of normal bereavement. Am J Psychiatry. 1968;125:168–78.

    Article  CAS  PubMed  Google Scholar 

  80. Zisook S, Shuchter SR, Sledge PA, Paulus M, Judd LL. The spectrum of depressive phenomena after spousal bereavement. J Clin Psychiatry. 1994;55:29–36.

    PubMed  Google Scholar 

  81. Monk TH, Germain A, Reynolds CF. Sleep disturbance in Bereavement. Psychiatr Ann. 2008;38:671–75.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Martikainen P, Valkonen T. Mortality after the death of a spouse: rates and causes of death in a large Finnish cohort. Am J Public Health. 1996;86:1087–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Hart CL, Hole DJ, Lawlor DA, Smith GD, Lever TF. Effect of conjugal bereavement on mortality of the bereaved spouse in participants of the Renfrew/Paisley Study. J Epidemiol Community Health. 2007;61:455–60.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Mostofsky E, Maclure M, Sherwood JB, Tofler GH, Muller JE, Mittleman MA. Risk of acute myocardial infarction after the death of a significant person in one’s life: the Determinants of Myocardial Infarction Onset Study. Circulation. 2012;125:491–6.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Hoffmann BM, Blair NP, McAuliffe TL, Hwang G, Larson E, Claesges SA, et al. Neuropsychological correlates of early grief in bereaved older adults. Int Psychogeriatr. 2024;36:1064–69.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Grimby A, Johansson AK. Factors related to alcohol and drug consumption in Swedish widows. Am J Hosp Palliat Care. 2009;26:8–12.

    Article  PubMed  Google Scholar 

  87. Stahl ST, Schulz R. Changes in routine health behaviors following late-life bereavement: a systematic review. J Behav Med. 2014;37:736–55.

    Article  PubMed  Google Scholar 

  88. Jones MP, Bartrop RW, Forcier L, Penny R. The long-term impact of bereavement upon spouse health: a 10-year follow-up. Acta Neuropsychiatr. 2010;22:212–7.

    Article  PubMed  Google Scholar 

  89. van den Berg GJ, Lindeboom M, Portrait F. Conjugal bereavement effects on health and mortality at advanced ages. J Health Econ. 2011;30:774–94.

    Article  PubMed  Google Scholar 

  90. Knowles LM, Ruiz JM, O’Connor MF. A Systematic Review of the Association Between Bereavement and Biomarkers of Immune Function. Psychosom Med. 2019;81:415–33.

    Article  PubMed  Google Scholar 

  91. Shah SM, Carey IM, Harris T, DeWilde S, Victor CR, Cook DG. Do good health and material circumstances protect older people from the increased risk of death after bereavement?. Am J Epidemiol. 2012;176:689–98.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Cozza SJ, Shear MK, Reynolds CF, Fisher JE, Zhou J, Maercker A, et al. Optimizing the clinical utility of four proposed criteria for a persistent and impairing grief disorder by emphasizing core, rather than associated symptoms. Psychol Med. 2020;50:438–45.

    Article  PubMed  Google Scholar 

  93. Smid GE, Boelen PA. Performance of Complicated Grief Criteria. Am J Psychiatry. 2016;173:1149.

    Article  PubMed  Google Scholar 

  94. Goveas JS, Shear MK. Grief and the COVID-19 Pandemic in Older Adults. Am J Geriatr Psychiatry. 2020;28:1119–25.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Lundorff M, Holmgren H, Zachariae R, Farver-Vestergaard I, O’Connor M. Prevalence of prolonged grief disorder in adult bereavement: A systematic review and meta-analysis. J Affect Disord. 2017;212:138–49.

    Article  PubMed  Google Scholar 

  96. Neria Y, Gross R, Litz B, Maguen S, Insel B, Seirmarco G, et al. Prevalence and psychological correlates of complicated grief among bereaved adults 2.5-3.5 years after September 11th attacks. J Trauma Stress. 2007;20:251–62.

    Article  PubMed  Google Scholar 

  97. Tal I, Mauro C, Reynolds CF 3rd, Shear MK, Simon N, Lebowitz B, et al. Complicated grief after suicide bereavement and other causes of death. Death Stud. 2017;41:267–75.

    Article  PubMed  Google Scholar 

  98. Djelantik A, Smid GE, Mroz A, Kleber RJ, Boelen PA. The prevalence of prolonged grief disorder in bereaved individuals following unnatural losses: Systematic review and meta regression analysis. J Affect Disord. 2020;265:146–56.

    Article  PubMed  Google Scholar 

  99. Na PJ, Fischer IC, Shear KM, Pietrzak RH. Prevalence, correlates, and psychiatric burden of Prolonged Grief disorder in U.S. Military Veterans: results from a nationally representative study. Am J Geriatr Psychiatry. 2023;31:543–48.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Buur C, Zachariae R, Komischke-Konnerup KB, Marello MM, Schierff LH, O’Connor M. Risk factors for prolonged grief symptoms: a systematic review and meta-analysis. Clin Psychol Rev. 2024;107:102375.

    Article  CAS  PubMed  Google Scholar 

  101. Lobb EA, Kristjanson LJ, Aoun SM, Monterosso L, Halkett GK, Davies A. Predictors of complicated grief: a systematic review of empirical studies. Death Stud. 2010;34:673–98.

    Article  PubMed  Google Scholar 

  102. Meert KL, Donaldson AE, Newth CJ, Harrison R, Berger J, Zimmerman J, et al. Complicated grief and associated risk factors among parents following a child’s death in the pediatric intensive care unit. Arch Pediatr Adolesc Med. 2010;164:1045–51.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Charney ME, Bui E, Sager JC, Ohye BY, Goetter EM, Simon NM. Complicated Grief Among Military Service Members and Veterans Who Served After September 11, 2001. J Trauma Stress. 2018;31:157–62.

    Article  PubMed  Google Scholar 

  104. Simon NM, O’Day EB, Hellberg SN, Hoeppner SS, Charney ME, Robinaugh DJ, et al. The loss of a fellow service member: Complicated grief in post-9/11 service members and veterans with combat-related posttraumatic stress disorder. J Neurosci Res. 2018;96:5–15.

    Article  CAS  PubMed  Google Scholar 

  105. Marques L, Bui E, LeBlanc N, Porter E, Robinaugh D, Dryman MT, et al. Complicated grief symptoms in anxiety disorders: prevalence and associated impairment. Depress Anxiety. 2013;30:1211–6.

    Article  PubMed  Google Scholar 

  106. Piper WE, Ogrodniczuk JS, Azim HF, Weideman R. Prevalence of loss and complicated grief among psychiatric outpatients. Psychiatr Serv. 2001;52:1069–74.

    Article  CAS  PubMed  Google Scholar 

  107. Patel SR, Cole A, Little V, Skritskaya NA, Lever E, Dixon LB, et al. Acceptability, feasibility and outcome of a screening programme for complicated grief in integrated primary and behavioural health care clinics. Fam Pr. 2019;36:125–31.

    Article  Google Scholar 

  108. Simon NM, Shear KM, Thompson EH, Zalta AK, Perlman C, Reynolds CF, et al. The prevalence and correlates of psychiatric comorbidity in individuals with complicated grief. Compr Psychiatry. 2007;48:395–9.

    Article  PubMed  Google Scholar 

  109. Simon NM, Wall MM, Keshaviah A, Dryman MT, LeBlanc NJ, Shear MK. Informing the symptom profile of complicated grief. Depress Anxiety. 2011;28:118–26.

    Article  PubMed  Google Scholar 

  110. Bui E, Horenstein A, Shah R, Skritskaya NA, Mauro C, Wang Y, et al. Grief-related panic symptoms in Complicated Grief. J Affect Disord. 2015;170:213–6.

    Article  PubMed  Google Scholar 

  111. Hall CA, Reynolds CF 3rd, Butters M, Zisook S, Simon N, Corey-Bloom J, et al. Cognitive functioning in complicated grief. J Psychiatr Res. 2014;58:20–5.

    Article  PubMed  Google Scholar 

  112. Nasreddine ZS, Phillips N, Chertkow H. Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sample. Neurology. 2012;78:765–6.

    Article  PubMed  Google Scholar 

  113. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168:1266–77.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Zisook S, Corruble E, Duan N, Iglewicz A, Karam EG, Lanouette N, et al. The bereavement exclusion and DSM-5. Depress Anxiety. 2012;29:425–43.

    Article  PubMed  Google Scholar 

  115. First MB, Williams JBW, Karg RS, Spitzer RL. Structured clinical interview for DSM-5_Research Version (SCID-5 for DSM-5, Research Version; SCID-5-RV, Version 1.0.0). Arlington, VA: American Psychiatric Association; 2015.

  116. Zisook S, Shear MK, Reynolds CF, Simon NM, Mauro C, Skritskaya NA, et al. Treatment of complicated grief in survivors of suicide loss: a HEAL report. J Clin Psychiatry. 2018;79:17m11592.

  117. Supiano KP, Luptak M. Complicated grief in older adults: a randomized controlled trial of complicated grief group therapy. Gerontologist. 2014;54:840–56.

    Article  PubMed  Google Scholar 

  118. Bryant RA, Kenny L, Joscelyne A, Rawson N, Maccallum F, Cahill C, et al. Treating prolonged grief disorder: a randomized clinical trial. JAMA Psychiatry. 2014;71:1332–9.

    Article  PubMed  Google Scholar 

  119. Bryant RA, Azevedo S, Yadav S, Cahill C, Kenny L, Maccallum F, et al. Cognitive behavior therapy vs mindfulness in treatment of prolonged grief disorder: a randomized clinical trial. JAMA Psychiatry. 2024;81:646–54.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Acierno R, Kauffman B, Muzzy W, Tejada MH, Lejuez C. Behavioral activation and therapeutic exposure vs. cognitive therapy for grief among combat veterans: a randomized clinical trial of bereavement interventions. Am J Hosp Palliat Care. 2021;38:1470–78.

    Article  PubMed  Google Scholar 

  121. Rosner R, Pfoh G, Kotoucova M, Hagl M. Efficacy of an outpatient treatment for prolonged grief disorder: a randomized controlled clinical trial. J Affect Disord. 2014;167:56–63.

    Article  PubMed  Google Scholar 

  122. Kaiser J, Nagl M, Hoffmann R, Linde K, Kersting A. Therapist-assisted web-based intervention for prolonged grief disorder after cancer bereavement: randomized controlled trial. JMIR Ment Health. 2022;9:e27642.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Komischke-Konnerup KB, Zachariae R, Boelen PA, Marello MM, O’Connor M. Grief-focused cognitive behavioral therapies for prolonged grief symptoms: a systematic review and meta-analysis. J Consult Clin Psychol. 2024;92:236–48.

    Article  PubMed  Google Scholar 

  124. Knowles LM, Jovel KS, Mayer CM, Bottrill KC, Kaszniak AW, Sbarra DA, et al. A controlled trial of two mind-body interventions for grief in widows and widowers. J Consult Clin Psychol. 2021;89:640–54.

    Article  PubMed  Google Scholar 

  125. Stahl ST, Emanuel J, Albert SM, Dew MA, Schulz R, Robbins-Welty G, et al. Design and rationale for a technology-based healthy lifestyle intervention in older adults grieving the loss of a spouse. Contemp Clin Trials Commun. 2017;8:99–105.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Lichtenthal WG, Catarozoli C, Masterson M, Slivjak E, Schofield E, Roberts KE, et al. An open trial of meaning-centered grief therapy: rationale and preliminary evaluation. Palliat Support Care. 2019;17:2–12.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Huberty J, Sullivan M, Green J, Kurka J, Leiferman J, Gold K, et al. Online yoga to reduce post traumatic stress in women who have experienced stillbirth: a randomized control feasibility trial. BMC Complement Med Ther. 2020;20:173.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Williams J, Shorter GW, Howlett N, Zakrzewski-Fruer J, Chater AM. Can physical activity support grief outcomes in individuals who have been bereaved? A systematic review. Sports Med Open. 2021;7:26.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Davidow JB, Zide BS, Levin LL, Biddle KD, Urizar JC, Donovan NJ. A Scoping Review of Interventions for Spousal Bereavement in Older Adults. Am J Geriatr Psychiatry. 2022;30:404–18.

    Article  PubMed  Google Scholar 

  130. Uneno Y, Kotera Y, Kikuchi K, Yamada M, Sugitani M, Terado S, et al. Self-compassion-based online group psychotherapy for bereavement-related grief: the COMPACT feasibility trial. Gen Hosp Psychiatry. 2024;90:116–23.

    Article  PubMed  Google Scholar 

  131. Calderon A, Irwin M, Simon NM, Shear MK, Mauro C, Zisook S, et al. Depression is associated with treatment response trajectories in adults with Prolonged Grief Disorder: a machine learning analysis. J Affect Disord. 2025;388:119536.

    Article  PubMed  Google Scholar 

  132. Gang J, Kocsis J, Avery J, Maciejewski PK, Prigerson HG. Naltrexone treatment for prolonged grief disorder: study protocol for a randomized, triple-blinded, placebo-controlled trial. Trials. 2021;22:110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Thieleman K, Cacciatore J, Thomas S. Impairing social connectedness: the dangers of treating grief with naltrexone. J Humanist Psychol. 2023;63:267–75.

    Article  Google Scholar 

  134. Goveas JS, O’Connor MF. Prolonged Grief Disorder: unveiling neurobiological mechanisms for a shared path forward. Am J Geriatr Psychiatry. 2024;32:535–38.

    Article  PubMed  Google Scholar 

  135. Sridharan D, Levitin DJ, Menon V. A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proc Natl Acad Sci USA. 2008;105:12569–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011;15:483–506.

    Article  PubMed  Google Scholar 

  137. McTeague LM, Goodkind MS, Etkin A. Transdiagnostic impairment of cognitive control in mental illness. J Psychiatr Res. 2016;83:37–46.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Tadayonnejad R, Ajilore O. Brain network dysfunction in late-life depression: a literature review. J Geriatr Psychiatry Neurol. 2014;27:5–12.

    Article  PubMed  Google Scholar 

  139. Andreescu C, Ajilore O, Aizenstein HJ, Albert K, Butters MA, Landman BA, et al. Disruption of neural homeostasis as a model of relapse and recurrence in late-life depression. Am J Geriatr Psychiatry. 2019;27:1316–30.

  140. Bressler SL, Menon V. Large-scale brain networks in cognition: emerging methods and principles. Trends Cogn Sci. 2010;14:277–90.

    Article  PubMed  Google Scholar 

  141. Menon V. The triple network model, insight, and large-scale brain organization in autism. Biol Psychiatry. 2018;84:236–38.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Menon B. Towards a new model of understanding—the triple network, psychopathology and the structure of the mind. Med Hypotheses. 2019;133:109385.

    Article  PubMed  Google Scholar 

  143. Menon V. Brain networks and cognitive impairment in psychiatric disorders. World Psychiatry. 2020;19:309–10.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007;27:2349–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Craig AD. How do you feel-now? The anterior insula and human awareness. Nat Rev Neurosci. 2009;10:59–70.

    Article  CAS  PubMed  Google Scholar 

  146. Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci. 2000;4:215–22.

    Article  CAS  PubMed  Google Scholar 

  147. Blair NP, Hwang G, Ward BD, Claesges SA, Webber AR, Hainsworth KR, et al. Disrupted large-scale brain network connectivity in prolonged grief disorder: relationship with grief-related avoidance, yearning, and intrusive thoughts. Biol Psychiatry Cogn Neurosci Neuroimaging. 2025;S2451-9022:00227–7.

  148. Hofer MA. On the nature and consequences of early loss. Psychosom Med. 1996;58:570–81.

    Article  CAS  PubMed  Google Scholar 

  149. Insel TR. Is social attachment an addictive disorder?. Physiol Behav. 2003;79:351–7.

    Article  CAS  PubMed  Google Scholar 

  150. Wise RA. Drug-activation of brain reward pathways. Drug Alcohol Depend. 1998;51:13–22.

    Article  CAS  PubMed  Google Scholar 

  151. Haber SN, Knutson B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology. 2010;35:4–26.

    Article  PubMed  Google Scholar 

  152. Wang KS, Smith DV, Delgado MR. Using fMRI to study reward processing in humans: past, present, and future. J Neurophysiol. 2016;115:1664–78.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Suckling J, Nestor LJ. The neurobiology of addiction: the perspective from magnetic resonance imaging present and future. Addiction. 2017;112:360–69.

    Article  PubMed  Google Scholar 

  154. O’Connor MF, Wellisch DK, Stanton AL, Eisenberger NI, Irwin MR, Lieberman MD. Craving love? Enduring grief activates brain’s reward center. Neuroimage. 2008;42:969–72.

    Article  PubMed  Google Scholar 

  155. Kakarala SE, Roberts KE, Rogers M, Coats T, Falzarano F, Gang J, et al. The neurobiological reward system in Prolonged Grief Disorder (PGD): a systematic review. Psychiatry Res Neuroimaging. 2020;303:111135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Blair NP, Cohen AD, Ward BD, Claesges SA, Agarwal M, Wang Y, et al. Ventral striatal subregional dysfunction in late-life grief: relationships with yearning and depressive symptoms. J Psychiatr Res. 2022;156:252–60.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Eisma MC, Stroebe MS. Emotion regulatory strategies in complicated grief: a systematic review. Behav Ther. 2021;52:234–49.

    Article  PubMed  Google Scholar 

  158. Pessoa L, Adolphs R. Emotion processing and the amygdala: from a ‘low road’ to ‘many roads’ of evaluating biological significance. Nat Rev Neurosci. 2010;11:773–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Cahill L, McGaugh JL. Mechanisms of emotional arousal and lasting declarative memory. Trends Neurosci. 1998;21:294–9.

    Article  CAS  PubMed  Google Scholar 

  160. Hamann S. Cognitive and neural mechanisms of emotional memory. Trends Cogn Sci. 2001;5:394–400.

    Article  CAS  PubMed  Google Scholar 

  161. Fernandez-Alcantara M, Verdejo-Roman J, Cruz-Quintana F, Perez-Garcia M, Catena-Martinez A, Fernandez-Avalos MI, et al. Increased amygdala activations during the emotional experience of death-related pictures in complicated grief: an fMRI study. J Clin Med. 2020;9:851.

  162. Hwang G, Blair NP, Ward BD, McAuliffe TL, Claesges SA, Webber AR, et al. Amygdala-centered emotional processing in prolonged grief disorder: relationship with clinical symptomatology. Biol Psychiatry Cogn Neurosci Neuroimaging. 2025;10:1284–93.

  163. Raichle ME, Snyder AZ. A default mode of brain function: a brief history of an evolving idea. Neuroimage. 2007;37:1083–90.

    Article  PubMed  Google Scholar 

  164. Raichle ME. The brain’s default mode network. Annu Rev Neurosci. 2015;38:433–47.

    Article  CAS  PubMed  Google Scholar 

  165. Menon V. 20 years of the default mode network: a review and synthesis. Neuron. 2023;111:2469–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Niendam TA, Laird AR, Ray KL, Dean YM, Glahn DC, Carter CS. Meta-analytic evidence for a superordinate cognitive control network subserving diverse executive functions. Cogn Affect Behav Neurosci. 2012;12:241–68.

    Article  PubMed  PubMed Central  Google Scholar 

  167. Cole MW, Schneider W. The cognitive control network: Integrated cortical regions with dissociable functions. Neuroimage. 2007;37:343–60.

    Article  PubMed  Google Scholar 

  168. Chen G, Ward BD, Claesges SA, Li SJ, Goveas JS. Amygdala functional connectivity features in grief: a pilot longitudinal study. Am J Geriatr Psychiatry. 2020;28:1089–101.

    Article  PubMed  PubMed Central  Google Scholar 

  169. McConnell MH, Killgore WDS, O’Connor MF. Yearning predicts subgenual anterior cingulate activity in bereaved individuals. Heliyon. 2018;4:e00852.

    Article  PubMed  PubMed Central  Google Scholar 

  170. Gundel H, O’Connor MF, Littrell L, Fort C, Lane RD. Functional neuroanatomy of grief: an FMRI study. Am J Psychiatry. 2003;160:1946–53.

    Article  PubMed  Google Scholar 

  171. O’Connor MF, Gundel H, McRae K, Lane RD. Baseline vagal tone predicts BOLD response during elicitation of grief. Neuropsychopharmacology. 2007;32:2184–9.

    Article  PubMed  Google Scholar 

  172. Kersting A, Ohrmann P, Pedersen A, Kroker K, Samberg D, Bauer J, et al. Neural activation underlying acute grief in women after the loss of an unborn child. Am J Psychiatry. 2009;166:1402–10.

    Article  PubMed  Google Scholar 

  173. Freed PJ, Yanagihara TK, Hirsch J, Mann JJ. Neural mechanisms of grief regulation. Biol Psychiatry. 2009;66:33–40.

    Article  PubMed  PubMed Central  Google Scholar 

  174. Schneck N, Haufe S, Tu T, Bonanno GA, Ochsner K, Sajda P, et al. Tracking Deceased-Related Thinking with Neural Pattern Decoding of a Cortical-Basal Ganglia Circuit. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017;2:421–29.

    PubMed  PubMed Central  Google Scholar 

  175. Schneck N, Tu T, Bonanno GA, Shear MK, Sajda P, Mann JJ. Self-generated Unconscious Processing of Loss Linked to Less Severe Grieving. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019;4:271–79.

    PubMed  Google Scholar 

  176. Schneck N, Tu T, Haufe S, Bonanno GA, GalfaIvy H, Ochsner KN, et al. Ongoing monitoring of mindwandering in avoidant grief through cortico-basal-ganglia interactions. Soc Cogn Affect Neurosci. 2019;14:163–72.

    Article  PubMed  Google Scholar 

  177. Schneck N, Tu T, Michel CA, Bonanno GA, Sajda P, Mann JJ. Attentional Bias to Reminders of the Deceased as Compared With a Living Attachment in Grieving. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:107–15.

    PubMed  Google Scholar 

  178. Michel CA, Mann JJ, Schneck N. Neural correlates of deceased-related attention during acute grief in suicide-related bereavement. J Affect Disord. 2024;347:285–92.

    Article  PubMed  Google Scholar 

  179. Arizmendi B, Kaszniak AW, O’Connor MF. Disrupted prefrontal activity during emotion processing in complicated grief: An fMRI investigation. Neuroimage. 2016;124:968–76.

    Article  PubMed  Google Scholar 

  180. Bryant RA, Andrew E, Korgaonkar MS. Distinct neural mechanisms of emotional processing in prolonged grief disorder. Psychol Med. 2021;51:587–95.

    Article  PubMed  Google Scholar 

  181. Shi Y, Shi G, Zhao S, Wang B, Yang Y, Li H, et al. Atrophy in the supramarginal gyrus associated with impaired cognitive inhibition in grieving Chinese Shidu parents. Eur J Psychotraumatol. 2024;15:2403250.

    Article  PubMed  PubMed Central  Google Scholar 

  182. Kim JW, Byun MS, Lee JH, Yi D, Kim MJ, Jung G, et al. Spouse bereavement and brain pathologies: A propensity score matching study. Psychiatry Clin Neurosci. 2022;76:490–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Saavedra, Perez HC, Ikram MA, Direk N, Prigerson HG, Freak-Poli R, et al. Cognition, structural brain changes and complicated grief. A population-based study. Psychol Med. 2015;45:1389–99.

    Article  Google Scholar 

  184. Acosta H, Jansen A, Kircher T. Larger bilateral amygdalar volumes are associated with affective loss experiences. J Neurosci Res. 2021;99:1763–79.

    Article  CAS  PubMed  Google Scholar 

  185. Yoshiike T, Benedetti F, Moriguchi Y, Vai B, Aggio V, Asano K, et al. Exploring the role of empathy in prolonged grief reactions to bereavement. Sci Rep. 2023;13:7596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Liu W, Liu H, Wei D, Sun J, Yang J, Meng J, et al. Abnormal degree centrality of functional hubs associated with negative coping in older Chinese adults who lost their only child. Biol Psychol. 2015;112:46–55.

    Article  PubMed  Google Scholar 

  187. Seeley SH, Andrews-Hanna JR, Allen JJB, O’Connor MF. Dwelling in prolonged grief: Resting state functional connectivity during oxytocin and placebo administration. Hum Brain Mapp. 2023;44:245–57.

    Article  PubMed  Google Scholar 

  188. Maccallum F, Bryant RA. Attentional bias in complicated grief. J Affect Disord. 2010;125:316–22.

    Article  PubMed  Google Scholar 

  189. Mancini AD, Bonanno GA. The persistence of attachment: complicated grief, threat, and reaction times to the deceased’s name. J Affect Disord. 2012;139:256–63.

    Article  PubMed  PubMed Central  Google Scholar 

  190. Maccallum F, Bryant RA. Impaired autobiographical memory in complicated grief. Behav Res Ther. 2010;48:328–34.

    Article  PubMed  Google Scholar 

  191. Maccallum F, Bryant RA. Imagining the future in complicated grief. Depress Anxiety. 2011;28:658–65.

    Article  PubMed  Google Scholar 

  192. Maccallum F, Bonanno GA. The economics of losing a loved one: delayed reward discounting in prolonged grief. Clin Psychol Sci. 2016;4:683–90.

    Article  Google Scholar 

  193. Maccallum F, Bonanno GA. Social trust and the discounting of gains and losses in prolonged grief. J Psychiatr Res. 2022;147:148–53.

    Article  PubMed  Google Scholar 

  194. Maccallum F, Sawday S, Rinck M, Bryant RA. The push and pull of grief: Approach and avoidance in bereavement. J Behav Ther Exp Psychiatry. 2015;48:105–9.

    Article  PubMed  Google Scholar 

  195. Eisma MC, de Lang TA, Christodoulou K, Schmitt LO, Boelen PA, de Jong PJ. Prolonged grief symptoms and lingering attachment predict approach behavior toward the deceased. J Trauma Stress. 2025;38:284–95.

    Article  PubMed  PubMed Central  Google Scholar 

  196. Eisma MC, Rinck M, Stroebe MS, Schut HA, Boelen PA, Stroebe W, et al. Rumination and implicit avoidance following bereavement: an approach avoidance task investigation. J Behav Ther Exp Psychiatry. 2015;47:84–91.

    Article  PubMed  Google Scholar 

  197. Dosenbach NUF, Raichle ME, Gordon EM. The brain’s action-mode network. Nat Rev Neurosci. 2025;26:158–68.

    Article  CAS  PubMed  Google Scholar 

  198. Corbetta M, Shulman GL. Control of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci. 2002;3:201–15.

    Article  CAS  PubMed  Google Scholar 

  199. Petersen SE, Posner MI. The attention system of the human brain: 20 years after. Annu Rev Neurosci. 2012;35:73–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106:1125–65.

    Article  PubMed  Google Scholar 

  201. Singer J, Goveas JS, Elliott L, Parmar H, Mary-Frances O. Personalized fMRI tasks for grief severity in bereaved individuals: Emotional counting Stroop and grief elicitation protocols. Psychiatry Res Neuroimaging. 2024;345:111902.

    Article  PubMed  Google Scholar 

  202. Buckley T, Mihailidou AS, Bartrop R, McKinley S, Ward C, Morel-Kopp MC, et al. Haemodynamic changes during early bereavement: potential contribution to increased cardiovascular risk. Heart Lung Circ. 2011;20:91–8.

    Article  PubMed  Google Scholar 

  203. Buckley T, Stannard A, Bartrop R, McKinley S, Ward C, Mihailidou AS, et al. Effect of early bereavement on heart rate and heart rate variability. Am J Cardiol. 2012;110:1378–83.

    Article  PubMed  Google Scholar 

  204. Chen MA, Suchting R, Thayer JF, Fagundes CP. Resilience to stress across the lifespan: childhood maltreatment, heart rate variability, and bereavement. Psychol Aging. 2023;38:247–62.

    Article  PubMed  PubMed Central  Google Scholar 

  205. Irwin M, Daniels M, Risch SC, Bloom E, Weiner H. Plasma cortisol and natural killer cell activity during bereavement. Biol Psychiatry. 1988;24:173–8.

    Article  CAS  PubMed  Google Scholar 

  206. Buckley T, Bartrop R, McKinley S, Ward C, Bramwell M, Roche D, et al. Prospective study of early bereavement on psychological and behavioural cardiac risk factors. Intern Med J. 2009;39:370–8.

    Article  CAS  PubMed  Google Scholar 

  207. Richardson VE, Bennett KM, Carr D, Gallagher S, Kim J, Fields N. How does bereavement get under the skin? The effects of late-life spousal loss on cortisol levels. J Gerontol B Psychol Sci Soc Sci. 2015;70:341–7.

    Article  PubMed  Google Scholar 

  208. Saavedra Perez HC, Direk N, Milic J, Ikram MA, Hofman A, Tiemeier H. The impact of complicated grief on diurnal cortisol levels two years after loss: a population-based study. Psychosom Med. 2017;79:426–33.

    Article  CAS  PubMed  Google Scholar 

  209. O’Connor MF, Wellisch DK, Stanton AL, Olmstead R, Irwin MR. Diurnal cortisol in Complicated and Non-Complicated Grief: slope differences across the day. Psychoneuroendocrinology. 2012;37:725–8.

    Article  PubMed  Google Scholar 

  210. Bosch OJ, Young LJ. Oxytocin and social relationships: from attachment to bond disruption. Curr Top Behav Neurosci. 2018;35:97–117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Bui E, Hellberg SN, Hoeppner SS, Rosencrans P, Young A, Ross RA, et al. Circulating levels of oxytocin may be elevated in complicated grief: a pilot study. Eur J Psychotraumatol. 2019;10:1646603.

    Article  PubMed  PubMed Central  Google Scholar 

  212. Arizmendi BJ, Seeley SH, Allen JJB, Killgore WDS, Andrews-Hanna J, Weihs K, et al. A pull to be close: The differentiating effects of oxytocin and grief stimulus type on approach behavior in complicated grief. Eur J Trauma Dissociation. 2023;7:100339.

  213. Jacobs SC, Mason JW, Kosten TR, Wahby V, Kasl SV, Ostfeld AM. Bereavement and catecholamines. J Psychosom Res. 1986;30:489–96.

    Article  CAS  PubMed  Google Scholar 

  214. O’Connor MF, Shear MK, Fox R, Skritskaya N, Campbell B, Ghesquiere A, et al. Catecholamine predictors of complicated grief treatment outcomes. Int J Psychophysiol. 2013;88:349–52.

    Article  PubMed  Google Scholar 

  215. Bartrop RW, Luckhurst E, Lazarus L, Kiloh LG, Penny R. Depressed lymphocyte function after bereavement. Lancet. 1977;1:834–6.

    Article  CAS  PubMed  Google Scholar 

  216. Phillips AC, Carroll D, Burns VE, Ring C, Macleod J, Drayson M. Bereavement and marriage are associated with antibody response to influenza vaccination in the elderly. Brain Behav Immun. 2006;20:279–89.

    Article  PubMed  Google Scholar 

  217. Vitlic A, Khanfer R, Lord JM, Carroll D, Phillips AC. Bereavement reduces neutrophil oxidative burst only in older adults: role of the HPA axis and immunesenescence. Immun Ageing. 2014;11:13.

    Article  PubMed  PubMed Central  Google Scholar 

  218. Buckley T, Morel-Kopp MC, Ward C, Bartrop R, McKinley S, Mihailidou AS, et al. Inflammatory and thrombotic changes in early bereavement: a prospective evaluation. Eur J Prev Cardiol. 2012;19:1145–52.

    Article  PubMed  Google Scholar 

  219. Gerra G, Monti D, Panerai AE, Sacerdote P, Anderlini R, Avanzini P, et al. Long-term immune-endocrine effects of bereavement: relationships with anxiety levels and mood. Psychiatry Res. 2003;121:145–58.

    Article  CAS  PubMed  Google Scholar 

  220. Schultze-Florey CR, Martinez-Maza O, Magpantay L, Breen EC, Irwin MR, Gundel H, et al. When grief makes you sick: bereavement induced systemic inflammation is a question of genotype. Brain Behav Immun. 2012;26:1066–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Fagundes CP, Murdock KW, LeRoy A, Baameur F, Thayer JF, Heijnen C. Spousal bereavement is associated with more pronounced ex vivo cytokine production and lower heart rate variability: Mechanisms underlying cardiovascular risk?. Psychoneuroendocrinology. 2018;93:65–71.

    Article  CAS  PubMed  Google Scholar 

  222. Fagundes CP, Brown RL, Chen MA, Murdock KW, Saucedo L, LeRoy A, et al. Grief, depressive symptoms, and inflammation in the spousally bereaved. Psychoneuroendocrinology. 2019;100:190–97.

    Article  PubMed  Google Scholar 

  223. Brown RL, LeRoy AS, Chen MA, Suchting R, Jaremka LM, Liu J, et al. Grief symptoms promote inflammation during acute stress among bereaved spouses. Psychol Sci. 2022;33:859–73.

    Article  PubMed  PubMed Central  Google Scholar 

  224. Chen MA, Brown RL, Chen JY, de Dios MA, Green CE, Heijnen CJ, et al. Childhood maltreatment, subjective social status, and health disparities in bereavement. Psychoneuroendocrinology. 2022;135:105595.

    Article  PubMed  Google Scholar 

  225. O’Connor MF, Irwin MR, Wellisch DK. When grief heats up: pro-inflammatory cytokines predict regional brain activation. Neuroimage. 2009;47:891–6.

    Article  PubMed  Google Scholar 

  226. Hillard CJ. Stress regulates endocannabinoid-CB1 receptor signaling. Semin Immunol. 2014;26:380–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Morena M, Patel S, Bains JS, Hill MN. Neurobiological Interactions Between Stress and the Endocannabinoid System. Neuropsychopharmacology. 2016;41:80–102.

    Article  CAS  PubMed  Google Scholar 

  228. Harfmann EJ, McAuliffe TL, Larson ER, Claesges SA, Sauber G, Hillard CJ, et al. Circulating endocannabinoid concentrations in grieving adults. Psychoneuroendocrinology. 2020;120:104801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Kang M, Bohorquez-Montoya L, McAuliffe T, Claesges SA, Blair NO, Sauber G, et al. Loneliness, circulating endocannabinoid concentrations, and grief trajectories in bereaved older adults: a longitudinal study. Front Psychiatry. 2021;12:783187.

    Article  PubMed  PubMed Central  Google Scholar 

  230. Simmons TC, Singh ALK, Bales KL. Effects of systemic endocannabinoid manipulation on social and exploratory behavior in prairie voles (Microtus ochrogaster). Psychopharmacol (Berl). 2021;238:293–304.

    Article  CAS  Google Scholar 

  231. Huang FY, Hsu AL, Chao YP, Shang CM, Tsai JS, Wu CW. Mindfulness-based cognitive therapy on bereavement grief: Alterations of resting-state network connectivity associate with changes of anxiety and mindfulness. Hum Brain Mapp. 2021;42:510–20.

    Article  PubMed  Google Scholar 

  232. Iyengar Yoga for Prolonged Grief Disorder. https://clinicaltrials.gov/study/NCT05026827. Accessed June 2 2025.

  233. Goveas JS, Hwang G, McAuliffe TL, Blair NP, Webber A, Claesges SA, et al. Iyengar yoga and health education interventions for prolonged grief disorder in later life: feasibility of a randomized controlled pilot trial. Sci Rep. 2025;15:44604.

  234. Dulberg Z, Dubey R, Cohen JD. Adapting to loss: a computational model of grief. Psychol Rev. https://doi.org/10.1037/rev0000567. 2025.

  235. Malgaroli M, Maccallum F, Bonanno GA. Machine yearning: How advances in computational methods lead to new insights about reactions to loss. Curr Opin Psychol. 2022;43:13–17.

    Article  PubMed  Google Scholar 

  236. Huys QJ, Maia TV, Frank MJ. Computational psychiatry as a bridge from neuroscience to clinical applications. Nat Neurosci. 2016;19:404–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Huys QJM, Browning M, Paulus MP, Frank MJ. Advances in the computational understanding of mental illness. Neuropsychopharmacology. 2021;46:3–19.

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported in part by grants from the National Institute of Mental Health (R01MH122490), Advancing Healthier Wisconsin (00003864), Costigan Foundation, and Sexton Family Foundation to JSG.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Joseph S. Goveas, Gyujoon Hwang & Nutta-on P. Blair

  2. National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA

    Elliot A. Stein

  3. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Charles F. Reynolds

Authors
  1. Joseph S. Goveas
    View author publications

    Search author on:PubMed Google Scholar

  2. Gyujoon Hwang
    View author publications

    Search author on:PubMed Google Scholar

  3. Nutta-on P. Blair
    View author publications

    Search author on:PubMed Google Scholar

  4. Elliot A. Stein
    View author publications

    Search author on:PubMed Google Scholar

  5. Charles F. Reynolds
    View author publications

    Search author on:PubMed Google Scholar

Contributions

All authors made substantive contributions to this review, including the conceptualization of the review and compilation of research articles and their interpretation. JSG wrote the initial draft; all authors were involved in revising it critically for important intellectual content and are accountable for the manuscript’s content.

Corresponding author

Correspondence to Joseph S. Goveas.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Goveas, J.S., Hwang, G., Blair, No.P. et al. Prolonged grief disorder in later life: advancing our understanding of biopsychosocial mechanisms to guide future personalized interventions. Neuropsychopharmacol. (2026). https://doi.org/10.1038/s41386-026-02329-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41386-026-02329-x

Search

Advanced search

Quick links