The neurobiological reward system in Prolonged Grief Disorder (PGD): A systematic review
Open accessAbstract
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 also appears that oxytocin signaling is altered in PGD, though the exact mechanism is unclear. Our findings appear to be consistent with, though not confirmative of, conceptualizing PGD as a disorder of reward, and identify directions for future research.
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There are links between characteristic symptoms of prolonged grief disorder, in particular profound yearning, and a differential pattern of activation of the neural reward system compared to normative grief.
“Research has started to shed light on the neural underpinnings of prolonged grief disorder, and this work has indicated links between characteristic symptoms of the disorder - in particular, profound yearning - and a differential pattern of activation of the neural reward system compared to normative grief 95 .”
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Biological mechanisms underlying widowhood's health consequences: Does diet play a role?
Fagundes, C. P., & Wu‐Chung, E. L. (2021) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2021.100058 · Cited by 15 · see citing works
Competitive neurocognitive processes following bereavement
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Lenferink, L. I. M., & O’Connor, M. (2023) · Psychological Medicine · doi:10.1017/s0033291723001101 · Cited by 12 · see citing works
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Sadino, J., & Donaldson, Z. (2024) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.15134 · Cited by 7 · see citing works
Prolonged grief symptoms and lingering attachment predict approach behavior toward the deceased
Eisma, M. C., de Lang, T. A., Christodoulou, K., Schmitt, L. O., Boelen, P. A., & de Jong, P. J. (2025) · Journal of Traumatic Stress · doi:10.1002/jts.23124 · Cited by 7 · see citing works
Grief, bereavement and prolonged grief disorder: scoping and mapping the evidence
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Exploring the role of empathy in prolonged grief reactions to bereavement
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The Iatrogenic Consequences of Medicalising Grief: Resetting the Research Agenda
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Narrative review of the potential for psychedelics to treat Prolonged Grief Disorder
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Grief and Prolonged Grief Disorder
(2023) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615379934 · Cited by 6 · see citing works
Sekowski, M. M., Ludwikowska-Świeboda, K., & Prigerson, H. G. (2024) · Psychiatria Polska · doi:10.12740/pp/159024 · Cited by 5 · see citing works
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Prolonged Grief Disorder: Treatment Approaches and the Spiritual Dimensions of Healing
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Is Prolonged Grief Disorder an Emotional Disorder?
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The nature of grief: implications for the neurobiology of emotion
Ratcliffe, M., & Velasco, P. (2024) · Neuroscience of Consciousness · doi:10.1093/nc/niae041 · Cited by 3 · see citing works
Chapter 7. Treatment of Prolonged Grief Disorder
Skritskaya, N. A., Charney, M. E., Simon, N. M., & Shear, M. K. (2023) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615379934.lg07 · Cited by 3 · see citing works
Les trajectoires du mourir et du deuil
Laflamme, D. (2020) · Frontières · doi:10.7202/1072748ar · Cited by 3 · see citing works
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A neurobiological perspective on prolonged grief disorder
Bryant, R. A., Breukelaar, I. A., & Korgaonkar, M. S. (2026) · Trends in Neurosciences · doi:10.1016/j.tins.2026.01.001 · Cited by 3 · see citing works
Clinical characteristics of patients with refractory non-epileptic seizures
Fullam, S., & Costello, D. J. (2024) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2024.109783 · Cited by 2 · see citing works
Symptoms of prolonged grief in chronic pain patients: Results of a cross-sectional study
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Unraveling the Neurobiology of Grief: Insights into Brain and Behavior–Narrative Review
Statharakos, N. (2025) · Brain Science Advances · doi:10.26599/bsa.2025.905001 · Cited by 1 · see citing works
Pedrinelli, V., Rimoldi, B., Conti, L., Bordacchini, A., Parrini, L., Betti, L., Giannaccini, G., Dell’Oste, V., & Carmassi, C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262411835 · Cited by 4 · see citing works
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Manevich, A., & Prigerson, H. G. (2026) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2026.08.021 · Cited by 1 · see citing works
Self-citationChambers, J. E. (2023) · Psychodynamic Psychiatry · doi:10.1521/pdps.2023.51.1.45 · Cited by 1 · see citing works
Goveas, J. S., Shear, M. K., & Simon, N. M. (2024) · Springer eBooks · doi:10.1007/978-3-030-51366-5_43 · Cited by 1 · see citing works
Chapter 2. Bereavement, Grief, and Prolonged Grief Disorder in Children and Adolescents
Cozza, S. J., & Ogle, C. M. (2023) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615379934.lg02 · Cited by 1 · see citing works
Cozza, S. J., & Fisher, J. E. (2023) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615379934.lg01 · Cited by 1 · see citing works
Chapter 4. Defining and Diagnosing Prolonged Grief Disorder
Maciejewski, P. K., & Prigerson, H. G. (2023) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615379934.lg04 · Cited by 1 · see citing works
Self-citationXiao, C., Zhu, B., & Wei, J. (2024) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2024.03.029 · Cited by 1 · see citing works
Appendix B. Structured Clinical Interview for Prolonged Grief Disorder
Prigerson, H. G., Viola, M., Lichtenthal, W. G., Rogers, M., Derry, H. M., She, W. J., Gordon-Elliott, J. S., & Maciejewski, P. K. (2023) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615379934.bm02 · Cited by 1 · see citing works
Self-citationWalter, H. (2021) · Nervenheilkunde · doi:10.1055/a-1650-2810
Scientism, Ethics and Evil: From Mens Rea to Cerebrum Reus
Palermo, M. T. (2022) · International Journal of Offender Therapy and Comparative Criminology · doi:10.1177/0306624x221104959
Being Through Loss: A Queer Performative Reckoning With Grief
Hansen, I. H. (2023) · doi:10.33540/1642
Goveas, J. S., Shear, M. K., & Simon, N. M. (2023) · Springer eBooks · doi:10.1007/978-3-030-42825-9_43-1
Closing in on Close Connections: A Reply to Thieleman et al.
Prigerson, H. G., Singer, J. P., & Killikelly, C. (2024) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2024.01.223
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Ione, A. (2024) · Springer eBooks · doi:10.1007/978-3-031-55440-7_1
Chapter 5. Clinically Relevant Correlates of Prolonged Grief Disorder
Maciejewski, P. K., & Prigerson, H. G. (2023) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615379934.lg05
Self-citationReynolds, C. F., Cozza, S. J., Maciejewski, P. K., Prigerson, H. G., Shear, M. K., Simon, N. M., Zisook, S., & Skritskaya, N. A. (2023) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615379934.lg08
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Chapter 3. Clinical Management of Bereaved Patients With and Without Prolonged Grief Disorder
Iglewicz, A., Clark, A., & Zisook, S. (2023) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615379934.lg03
Chapter 6. Epidemiology of Prolonged Grief Disorder
Maciejewski, P. K., & Prigerson, H. G. (2023) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615379934.lg06
Self-citationSpezifisch Belastungs-assoziierte Störungen
Hölzel, L. P., Röpke, S., Cionek-Szpak, E., & Ehring, T. W. (2024) · Springer eBooks · doi:10.1007/978-3-662-67687-5_10
(2025) · Elsevier eBooks · doi:10.1016/b978-3-437-21835-4.00116-5
Grief, trauma and pain: A conceptual framework and empirical investigation
Kokou‐Kpolou, C. K., Fernández‐Alcántara, M., & Piché, M. (2025) · European Journal of Trauma & Dissociation · doi:10.1016/j.ejtd.2025.100549
Motivational and Self-Regulatory Factors Associated With Yearning and Prolonged Grief Symptoms
Williams, J. L., Henschel, A. V., & Hardt, M. M. (2025) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0000000000001833
Dsouza, V. F., Reardon, B., & Giscombé, C. L. W. (2025) · Geriatric Nursing · doi:10.1016/j.gerinurse.2025.103438
Grief and Belief: Relationships Between Prolonged Grief, Existential Nihilism, and Well/Illbeing
Kaur, J., Halliday, S., & van Antwerpen, N. (2025) · Journal of Loss and Trauma · doi:10.1080/15325024.2025.2583190 · Cited by 1 · see citing works
When perception meets grief: how the brain reconstructs person networks in response to absence
Nowacka, A., Shapiro, A., Douglas, K. M., & Corballis, P. M. (2025) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsaf117
Brain-heart interactions in prolonged grief disorder
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A Bigger Type of Sadness: How Grief Changes the Brain
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Adaptation mechanisms to bereavement in elderly
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Neurobiology of Pet Loss Grief: A Review from a One Health Perspective
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- Authors
- Kakarala, S. E., Roberts, K. E., Rogers, M., Coats, T., Falzarano, F., Gang, J., Chilov, M., Avery, J., Maciejewski, P. K., Lichtenthal, W. G., & Prigerson, H. G.
- Affiliations
- Weill Cornell Medicine (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Prigerson, H.G.
- ORCID
- Venue
- Psychiatry Research: Neuroimaging
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 303
- Pages
- 111135
- ISSN
- 0925-4927 (ISSN-L)
- PMC
- PMC7442719
- OpenAlex
- W3040354786
- Cited by
- 85
- References
- 107
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 16 · 2023: 25 · 2022: 8 · 2021: 10 · 2020: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Psychiatry Research Neuroimaging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Social Sciences › Psychology › Clinical Psychology › Grief, Bereavement, and Mental Health
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Social Psychology › Death Anxiety and Social Exclusion
- Keywords
- prolonged grief disorder, reward systems, longing, amygdala, orbitofrontal cortex, posterior cingulate cortex, anterior cingulate cortex, nucleus accumbens, basal ganglia, insula, oxytocin signaling, bereavement
- MeSH terms
- Bereavement, Brain, Grief, Humans, Reward, Time Factors
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