The neurobiological reward system in Prolonged Grief Disorder (PGD): A systematic review

S E Kakarala, K E Roberts, M Rogers, T Coats, F Falzarano, J Gang, M Chilov, J Avery, P K Maciejewski, W G Lichtenthal, H G Prigerson, S E Kakarala, K E Roberts, M Rogers, T Coats, F Falzarano, J Gang, M Chilov, J Avery, P K Maciejewski, W G Lichtenthal, H G Prigerson

Abstract

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.

Keywords: Bereavement; Complicated Grief (CG); Neuroimaging; Nneurobiology; Prolonged Grief Disorder (PGD).

Conflict of interest statement

Conflicts of Interest Statement

Declarations of interest: none.

Copyright © 2020 Elsevier B.V. All rights reserved.

Figures

Figure 1:
Figure 1:
Key areas and pathways involved in neural reward signaling. (Image: JG, adapted from Wikimedia Commons. [Arias-Carrión O., Stamelou M., Murillo-Rodríguez E., Menéndez-González M., Pöppel E., 2010. Dopaminergic reward system: a short integrative review International Archives of Medicine 3, 24. doi:10.1186/1755-7682-3-24.])
Figure 2:
Figure 2:
PRISMA flow diagram outlining the systematic review process.

References

    1. Acosta H, Jansen A, Nuscheler B, Kircher T, 2018. A voxel-based morphometry study on adult attachment style and affective loss. Neuroscience 392, 219–229. doi: 10.1016/j.neuroscience.2018.06.045.
    1. Arias-Carrión O, Stamelou M, Murillo-Rodríguez E, Menéndez-González M, Pöppel E, 2010. Dopaminergic reward system: a short integrative review International Archives of Medicine 3, 24. doi:10.1186/1755-7682-3-24.
    1. Arizmendi B, 2018. The effect of intranasal oxytocin on neural functioning in widow(er)s. Dissertation Abstracts International: Section B: The Sciences and Engineering.
    1. Arizmendi B, Kaszniak AW, O’Connor MF, 2016. Disrupted prefrontal activity during emotion processing in complicated grief: An fMRI investigation. NeuroImage 124, 968–976. doi: 10.1016/j.neuroimage.2015.09.054.
    1. Berridge KC, Kringelbach ML, 2015. Pleasure systems in the brain. Neuron 86, 646–664. doi:10.1016/j.neuron.2015.02.018.
    1. Blandini F, Nappi G, Tassorelli C, Martignoni E, 2000. Functional changes of the basal ganglia circuitry in Parkinson’s disease. Prog Neurobio 62, 63–68. doi: 10.1016/s0301-0082(99)00067-2.
    1. Boelen PA, Prigerson HG, 2007. 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. 257, 444–52.
    1. Bosch OJ, Dabrowska J, Modi ME, Johnson ZV, Keebaugh AC, Barrett CE, Ahern TH, Guo J, Grinevich V, Rainnie DG, Neumann ID, Young LJ, 2016. Oxytocin in the nucleus accumbens shell reverses CRFR2-evoked passive stress-coping after partner loss in monogamous male prairie voles. Psychoneuroendocrinology 64: 66–78. doi: 10.1016/j.psyneuen.2015.11.011.
    1. Bosch OJ, Nair HP, Ahern TH, Neumann ID, Young LJ, 2009. The CRF system mediates increased passive stress-coping behavior following the loss of a bonded partner in a monogamous rodent. Neuropsychopharmacology 34(6): 1406–1415. doi: 10.1038/npp.2008.154.
    1. Bosch OJ, Young LJ, 2017. Oxytocin and Social Relationships: From Attachment to Bond Disruption In: Hurlemann R, Grinevich V (eds) Behavioral Pharmacology of Neuropeptides: Oxytocin. Current Topics in Behavioral Neurosciences, vol 35 Springer, Cham.
    1. Bowlby J, 1973. Attachment and Loss, volume II: Separation Anxiety and Anger. Basic Books.
    1. Bramer WM, Giustini D, de Jonge GB, Holland L, Bekhuis T, 2017. De-duplication of database search results for systematic reviews in EndNote [published correction appears in J Med Libr Assoc 105, 1]. J Med Libr Assoc 104, 240–243. doi:10.3163/1536-5050.104.3.014.
    1. Bryant RA, Andrew E, Korgaonkar MS, 2020. Distinct neural mechanisms of emotional processing in prolonged grief disorder. Psychological Medicine 2020, 1–9. doi: 10.1017/S0033291719003507.
    1. Bui E, Nadal-Vicens M, Simon NM, 2012. Pharmacological approaches to the treatment of complicated grief: rationale and a brief review of the literature. Dialogues Clin Neurosci 14, 149–57.
    1. Bui E, Hellberg SN, Hoeppner SS, Rosencrans P, Young A, Ross RA et al., 2019. Circulating levels of oxytocin may be elevated in complicated grief: A pilot study. European Journal of Psychotraumatology 10, 1646603. doi: 10.1080/20008198.2019.1646603.
    1. Chawarski MC, Zhou W, Schottenfeld RS, 2011. Behavioral drug and HIV risk reduction counseling (BDRC) in MMT programs in Wuhan, China: A pilot randomized clinical trial. Drug Alcohol Depend 115, 237–239. doi: 10.1016/j.drugalcdep.2010.09.024.
    1. Chen CY, Yen JY, Wang PW, Liu GC, Yen CF, Ko CH, 2016. Altered Functional Connectivity of the Insula and Nucleus Accumbens in Internet Gaming Disorder: A Resting State fMRI Study. European Addiction Research 22, 192–200. doi: 10.1159/000440716.
    1. Clark GA, 1995. Emotional learning: Fear and loathing in the amygdala. Current Biology 5, 246–248. doi: 10.1016/S0960-9822(95)00050-9.
    1. Coan JA, Schaefer HS, Davidson RJ, 2006. Lending a Hand: Social Regulation of the Neural Response to Threat. Psychological Science 17, 1032–1039. doi: 10.1111/j.1467-9280.2006.01832.x.
    1. Cooney RE, Joormann J,, Eugène F, Dennis EL, Gotlib IH, 2010. Neural correlates of rumination in depression. Cogn Affect Behav Neurosci 10, 77–100. doi: 10.3758/CABN.10.4.470
    1. Droutman V, Read SJ, Bechara A, 2015. Revisiting the role of the insula in addiction. Trends Cogn Sci 19, 414–420. doi: 10.1016/j.tics.2015.05.005.
    1. Dugosh K, Abraham A, Seymour B, McLoyd K, Chalk M, Festinger D, 2016. A Systematic Review on the Use of Psychosocial Interventions in Conjunction With Medications for the Treatment of Opioid Addiction. J Addict Med 10, 93–103. doi: 10.1097/ADM.0000000000000193.
    1. Eklund A, Nichols TE, Knutsson H 2016. Cluster failure: why fMRI inferences for spatial extent have inflated false-positive rates. Proc. Natl. Acad. Sci. U.S.A 113, 7900–7905. 10.1073/pnas.1602413113
    1. Edwards S, Koob GF, 2010. Neurobiology of dysregulated motivational systems in drug addiction. Future Neurol. 5, 393–401. doi: 10.2217/fnl.10.14.
    1. Eisma MC, Schut HAW, Stroebe MS, Boelen PA, van den Bout J, Stroebe W, 2015. Adaptive and maladaptive rumination after loss: A three‐wave longitudinal study. Br J Clin Psychol 54, 163–180. doi:10.1111/bjc.12067
    1. Fernández-Alcántara M, Verdejo-Román J, Cruz-Quintana F, Pérez-García M, Catena-Martínez A, Fernández-Ávalos MI et al., 2020. Increased amygdala activations during the emotional experience of death-related pictures in complicated grief: an fMRI study. Journal of Clinical Medicine 9, 851. doi: 10.3390/jcm9030851.
    1. Fernando AB, Murray JE, Milton AL, 2013. The amygdala: securing pleasure and avoiding pain. Front Behav Neurosci 7, 190. doi:10.3389/fnbeh.2013.00190.
    1. Field M, Munafò MR, Franken IH, 2009. A meta-analytic investigation of the relationship between attentional bias and subjective craving in substance abuse. Psychological bulletin 135, 589–607. doi: 10.1037/a0015843.
    1. Fisher HE, Brown LL, Aron A, Strong G, Mashek D, 2010. Reward, Addiction, and Emotion Regulation Systems Associated With Rejection in Love. Journal of Neurophysiology 104, 51–60. doi: 10.1152/jn.00784.2009.
    1. Floresco SB, 2015. The nucleus accumbens: an interface between cognition, emotion, and action. Annual Review of Psychology 66: 25–52. doi: 10.1146/annurev-psych-010213-115159
    1. Fogel A, Garvey A, 2007. Alive communication. Infant Behavior and Development 30, 251–257. doi: 10.1016/j.infbeh.2007.02.007.
    1. Fredriksson I, Jayaram-Lindström N, Wirf M et al., 2015. Evaluation of guanfacine as a potential medication for alcohol use disorder in long-term drinking rats: behavioral and electrophysiological findings. Neuropsychopharmacology 40, 1130–1140. doi: 10.1038/npp.2014.294
    1. Freed PJ, Yanagihara TK, Hirsch J, Mann JJ, 2009. Neural mechanisms of grief regulation. Biological Psychiatry 66, 33–40. doi: 10.1016/j.biopsych.2009.01.019.
    1. Goldstein RZ, Volkow ND, 2011. Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat Rev Neurosci 12, 652–669. doi: 10.1038/nrn3119.
    1. Gündel H, O’Connor MF, Littrell L, Fort C, Lane RD, 2003. Functional neuroanatomy of grief: An FMRI study. American Journal of Psychiatry 160, 1946–1953. doi: 10.1176/appi.ajp.160.11.1946.
    1. Helstrom AW, Blow FC, Slaymaker V, Kranzler HR, Leong S, Oslin D, 2016. Reductions in Alcohol Craving Following Naltrexone Treatment for Heavy Drinking. Alcohol and Alcoholism 51, 562–566. doi: 10.1093/alcalc/agw038.
    1. Hofman A, Grobbee DE, de Jong PT, van den Ouweland FA, 1991. Determinants of disease and disability in the elderly: the Rotterdam Elderly Study. European Journal of Epidemiology 7, 403–422. doi: 10.1007/bf00145007.
    1. Huang FY, Hsu AL, Hsu LM, Tsai JS, Huang CM, Chao YP et al., 2019. Mindfulness improves emotion regulation and executive control on bereaved individuals: an fMRI study. Frontiers in Human Neuroscience 12, 541. doi: 10.3389/fnhum.2018.00541.
    1. Hurlemann R and Scheele D, 2016. Dissecting the Role of Oxytocin in the Formation and Loss of Social Relationships. Biological Psychiatry 79, 185–193. doi: 10.1016/j.biopsych.2015.05.013.
    1. ICD-11 for Mortality and Statistics. 6B42 Prolonged Grief Disorder. . [Accessed March 23, 2020]
    1. Inagaki TK, 2018. Opioids and Social Connection. Current Directions in Psychological Science 27, 85–90. doi: 10.1177/0963721417735531.
    1. Jain FA, Connolly CG, Christov-Moore L, Leuchter AF, Abrams M, Ben-Yelles RW et al., 2019. Grief, mindfulness and neural predictors of improvement in family dementia caregivers. Frontiers in Human Neuroscience 13, 155. doi: 10.3389/fnhum.2019.00155.
    1. Jin F, Zheng P, Liu H, Guo H, Sun Z, 2018. Functional and anatomical connectivity-based parcellation of human cingulate cortex. Brain Behav 8, e01070. doi:10.1002/brb3.1070.
    1. Johnson ZV, Young LJ, 2015. Neurobiological mechanisms of social attachment and pair bonding. Curr Opin Behav Sci. 3, 38–44. doi: 10.1016/j.cobeha.2015.01.009.
    1. King LB, Walum H, Inoue K, Eyrich NW, Young LJ, 2016. Variation in the Oxytocin Receptor Gene Predicts Brain Region-Specific Expression and Social Attachment. Biol Psychiatry 80,160–169. doi:10.1016/j.biopsych.2015.12.008.
    1. Koob GF, Volkow ND, 2016. Neurobiology of addiction: a neurocircuitry analysis. The Lancet: Psychiatry 3, 760–773. doi: 10.1016/S2215-0366(16)00104-8.
    1. Krupitsky EM, Neznanova O, Masalov D, Burakov AM, Didenko T, Romanova T, 2007. Effect of Memantine on Cue-Induced Alcohol Craving in Recovering Alcohol-Dependent Patients. American Journal of Psychiatry 164, 519–523. doi: 10.1176/ajp.2007.164.3.519
    1. Lanciego JL, Luquin N, Obeso JA, 2012. Functional neuroanatomy of the basal ganglia. Cold Spring Harb Perspect Med 2, a009621. doi:10.1101/cshperspect.a009621.
    1. Latham AE, Prigerson HG, 2004. Suicidality and bereavement: complicated grief as psychiatric disorder presenting greatest risk for suicidality. Suicide Life Threat Behav. 34, 350–362. doi:10.1521/suli.34.4.350.53737.
    1. Leech R, Sharp DJ, 2014. The role of the posterior cingulate cortex in cognition and disease. Brain 137, 12–32. doi:10.1093/brain/awt162.
    1. LeRoy AS, Knee CR, Derrick JL, Fagundes CP, 2019. Implications for Reward Processing in Differential Responses to Loss: Impacts on Attachment Hierarchy Reorganization. Personality and Social Psychology Review 23, 391–405. doi: 10.1177/1088868319853895.
    1. Lundorff M, Holmgren H, Zachariae R, Farver-Vestergaard I, O’Connor M, 2017. Prevalence of prolonged grief disorder in adult bereavement: A systematic review and meta-analysis. J Affect Disord 212, 138–149. doi: 10.1016/j.jad.2017.01.030.
    1. MacCallum F, Bryant RA, 2010. Attentional bias in complicated grief. J Affect Disord 125, 1–3. doi:10.1016/j.jad.2010.01.070.
    1. MacCallum F, Bryant RA, 2020. A Network Approach to Understanding Quality of Life Impairments in Prolonged Grief Disorder. J Trauma Stress 33, 106–115.
    1. MacCallum F, Sawday S, Rinck M, Bryant RA, 2015. The push and pull of grief: Approach and avoidance in bereavement. J Behav Ther Exp Psychiatry 48, 105–109. doi: 10.1016/j.jbtep.2015.02.010.
    1. Maciejewski PK, Maercker A, Boelen PA, Prigerson HG, 2016. “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 15, 266–275. doi: 10.1002/wps.20348.
    1. McConnell MH, Killgore WD, O’Connor MF, 2018. Yearning predicts subgenual anterior cingulate activity in bereaved individuals. Heliyon 4, e00852. doi: 10.1016/j.heliyon.2018.e00852.
    1. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M et al., 2015. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4, 1. doi:10.1186/2046-4053-4-1.
    1. Moore BA, Fazzino T, Barry DT et al., 2013. The Recovery Line: A pilot trial of automated, telephone-based treatment for continued drug use in methadone maintenance. J Subst Abuse Treat 45, 63–69. doi: 10.1016/j.jsat.2012.12.011.
    1. Mouaffak F, Leite C, Hamzaoui S, Benyamina A, Laqueille X, Kebir O, 2017. Naltrexone in the treatment of broadly defined behavioral addictions: a review and meta-analysis of randomized controlled trials. European Addiction Research 23, 204–210. doi: 10.1159/000480539.
    1. Najib A, Lorberbaum JP, Kose S, Bohning DE, George MS, 2004. Regional brain activity in women grieving a romantic relationship breakup. American Journal of Psychiatry 161, 12:2245–2256. doi: 10.1176/appi.ajp.161.12.2245.
    1. Naqvi NH, Bechara A, 2009. The hidden island of addiction: the insula. Trends Neurosci 32, 56–57. doi: 10.1016/j.tins.2008.09.009.
    1. Nieh EH, Kim SY, Namburi P, Tye KM, 2013. Optogenetic dissection of neural circuits underlying emotional valence and motivated behaviors. Brain Res 1511, 73–92. doi:10.1016/j.brainres.2012.11.001.
    1. Nielsen FA, Balslev D, Hansen LK, 2005. Mining the posterior cingulate: Segregation between memory and pain components. NeuroImage 27, 520–532. doi: 10.1016/j.neuroimage.2005.04.034.
    1. Noonan MP, Kolling N, Walton ME, Rushworth MF, 2012. Re-evaluating the role of the orbitofrontal cortex in reward and reinforcement. European Journal of Neuroscience 35, 997–1010. doi: 10.1111/j.1460-9568.2012.08023.x.
    1. Nyamathi AM, Nandy K, Greengold B et al., 2011. Effectiveness of intervention on improvement of drug use among methadone maintained adults. J Addict Dis 30, 6–16. doi: 10.1080/10550887.2010.531669.
    1. O’Connor MF, 2012. Immunological and neuroimaging biomarkers of complicated grief. Dialogues Clin Neurosci. 14, 141–8.
    1. O’Connor MF, 2018. Biobehavioral processes underlying complicated grief. Abstracts of the 76th Annual Scientific Meeting: Psychosomatic Medicine 80, A140. doi: 10.1097/PSY.0000000000000578.
    1. O’Connor MF, Arizmendi B, 2015. Approach and avoidance in complicated grief: neuroscience results and clinical implications. Journal of Psychosomatic Research 6, 78. doi: 10.1016/j.jpsychores.2015.03.100.
    1. O’Connor MF, Gündel H, McRae K, Lane RD, 2007. Baseline vagal tone predicts BOLD response during elicitation of grief. Neuropsychopharmacology 32, 2184–2189. doi: 10.1038/sj.npp.1301342.
    1. O’Connor MF, Irwin MR, Wellisch DK, 2009. When grief heats up: Pro-inflammatory cytokines predict regional brain activation. Neuroimage 47, 891–896. doi: 10.1016/j.neuroimage.2009.05.049.
    1. O’Connor MF, Shear MK, Fox R, Skritskaya N, Campbell B, Ghesquiere A et al., 2013. Catecholamine predictors of complicated grief treatment outcomes. International Journal of Psychophysiology 88, 349–352. doi: 10.1016/j.ijpsycho.2012.09.014.
    1. O’Connor MF, Wellisch DK, Stanton AL, Eisenberger NI, Irwin MR, Lieberman MD, 2008. Craving love? Enduring grief activates brain’s reward center. Neuroimage 42, 969–972. doi: 10.1016/j.neuroimage.2008.04.256.
    1. O’Neill HA, 2019. A review on the involvement of catecholamines in animal behaviour. South African Journal of Animal Science 49, 29–39. doi: 10.4314/sajas.v49i1.1
    1. Parisi A, Sharma A, Howard MO, Blank Wilson A, 2019. The relationship between substance misuse and complicated grief: A systematic review. J Subst Abuse Treat 103, 43–57.
    1. Price JL, Drevets WC, 2010. Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192–216. doi:10.1038/npp.2009.104
    1. Prigerson HG, Bierhals AJ, Kasl SV, Reynolds CF, Shear MK, Day N, Beery LC, Newsom JT, Jacobs S, 1997. Traumatic grief as a risk factor for mental and physical morbidity. Am J Psychiatry 154, 616–23.
    1. Prigerson HG, Horowitz MJ, Jacobs SC, Parkes CM, Aslan M, Goodkin K, Raphael B, Marwit SJ, Wortman C, Neimeyer RA, Bonanno GA, Block SD, Kissane D, Boelen P, Maercker A, Litz BT, Johnson JG, First MB, Maciejewski PK, 2009. Prolonged grief disorder: Psychometric validation of criteria proposed for DSM-V and ICD-11. PLoS Med. 2009, 6:e1000121. doi: 10.1371/journal.pmed.1000121.
    1. Prigerson HG, Jacobs SC, 2001. Traumatic grief as a distinct disorder: a rationale, consensus criteria, and preliminary empirical test In: Stroebe MS, Hansson RO, Stroebe W, Schut H (Eds.), Handbook of Bereavement Research: Consequences, Coping and Care. American Psychological Association, Washington, D.C. pp. 613–645.
    1. Roozendaal B, McEwen B,, Chattarji S, 2009. Stress, memory, and the amygdala. Nat Rev Neurosci 10, 423–433. doi: 10.1038/nrn2651.
    1. Prigerson HG, Bridge J, Maciejewski PK, Beery LC, Rosenheck RA, et al. 1999. Influence of traumatic grief on suicidal ideation among young adults. Am J Psychiatry 156: 1994–1995.
    1. Ruegsegger GN, Toedebusch RG, Childs TE, Grigsby KB, Booth FW, 2017. Loss of Cdk5 function in the nucleus accumbens decreases wheel running and may mediate age-related declines in voluntary physical activity. J Physiol 595, 363–384. doi:10.1113/JP272489.
    1. Saavedra Perez H, Ikram A, Direk N, Prigerson H, Freak-Poli R, Verhaaren B, et al., 2015. Cognition, structural brain changes and complicated grief. A population-based study. Psychological Medicine 45, 1389–1399. doi: 10.1017/s0033291714002499.
    1. Salamone JD, Correa M, Farrar A et al., 2007. Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology 191, 461–482. doi: 10.1007/s00213-006-0668-9.
    1. Sbarra DA, Hazan C, 2008. Coregulation, Dysregulation, Self-Regulation: An Integrative Analysis and Empirical Agenda for Understanding Adult Attachment, Separation, Loss, and Recovery. Personality and Social Psychology Review 12, 141–167. doi: 10.1177/1088868308315702.
    1. Schiele MA, Costa B, Abelli M, Martini C, Baldwin DS, Domschke K, et al., 2018. Oxytocin receptor gene variation, behavioural inhibition, and adult separation anxiety: Role in complicated grief. The World Journal of Biological Psychiatry 19, 471–479. doi: 10.1080/15622975.2018.1430374.
    1. Schneck N, Haufe S, Tu T, Bonanno GA, Ochsner KN, Sajda P et al., 2017. Tracking deceased-related thinking with neural pattern decoding of a cortical-basal ganglia circuit. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 2, 421–429. doi: 10.1016/j.bpsc.2017.02.004.
    1. Schneck N, Tu T, Michel CA, Bonanno GA, Sajda P, Mann JJ, 2018. Attentional bias to reminders of the deceased as compared with a living attachment in grieving. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 3, 107–115. doi: 10.1016/j.bpsc.2017.08.003.
    1. Schneck N, Tu T, Bonanno GA, Shear MK, Sajda P, Mann JJ, 2019a. Self-generated unconscious processing of loss linked to less severe grieving. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 4, 271–279. doi: 10.1016/j.bpsc.2018.08.003.
    1. Schneck N, Tu T, Haufe S, Bonanno GA, GalfaIvy H, Ochsner KN et al., 2019b. Ongoing monitoring of mindwandering in avoidant grief through cortico-basal-ganglia interactions. Social Cognitive and Affective neuroscience 14, 163–172. doi: 10.1093/scan/nsy114.
    1. Schoenbaum G, Shaham Y, 2008. The role of orbitofrontal cortex in drug addiction: a review of preclinical studies. Biol Psychiatry 63, 256–262. doi:10.1016/j.biopsych.2007.06.003.
    1. Stevens FL, Hurley RA, Taber KH, 2011. Anterior cingulate cortex: unique role in cognition and emotion. Journal of Neuropsychiatry and Clinical Neuroscience 23, 121–125. doi: 10.1176/jnp.23.2.jnp121.
    1. Silverman G Jacobs S, Kasl S, Shear M, Maciejewski P, Noaghuil S Prigerson H 2000. Quality of life impairments associated with diagnostic criteria for traumatic grief. Psychological Medicine, 30(4), 857–862. doi:10.1017/S0033291799002524
    1. Suckling J, Nestor LJ, 2017. The neurobiology of addiction: the perspective from magnetic resonance imaging present and future. Addiction 112, 360–369. doi:10.1111/add.13474.
    1. Tang W, Jbabdi S, Zhu Z et al., 2019. A connectional hub in the rostral anterior cingulate cortex links areas of emotion and cognitive control. Elife 8, e43761. doi:10.7554/eLife.43761.
    1. Tofler GH, Morel-Kopp MC, Spinaze M, Dent J, Ward C, McKinley S, et al. 2019. The effect of metoprolol and aspirin on cardiovascular risk in bereavement: A randomized controlled trial. Am Heart Journal 220:264–72. Epub 2020/01/11. doi: 10.1016/j.ahj.2019.11.003.
    1. Trezza V, Damsteegt R, Achterberg EJ,. Vanderschuren LJ, 2011. Nucleus accumbens μ-opioid receptors mediate social reward. J Neurosci. 31, 6362–70. doi: 10.1523/JNEUROSCI.5492-10.2011
    1. Tsurumi K, Kawada R, Yokoyama N et al., 2014. Insular activation during reward anticipation reflects duration of illness in abstinent pathological gamblers. Front Psychol 5, 1013. doi: 10.3389/fpsyg.2014.01013.
    1. Turner BO, Paul EJ, Miller MB et al., 2018. Small sample sizes reduce the replicability of task-based fMRI studies. Commun Biol 1, 62. doi: 10.1038/s42003-018-0073-z.
    1. Uddin LQ, Nomi JS, Hébert-Seropian B, Ghaziri J, Boucher O, 2017. Structure and Function of the Human Insula. J Clin Neurophysiol 34, 300–306. doi:10.1097/WNP.0000000000000377.
    1. Valstad M, Alvares GA, Egknud M, Matziorinis AM, Andreassen OA, Westlye LT, Quintana DS, 2017. The correlation between central and peripheral oxytocin concentrations: A systematic review and meta-analysis. Neuroscience Biobehavioral Reviews 78, 117–124. doi: 10.1016/j.neubiorev.2017.04.017.
    1. Volkow ND, Fowler S, 2000. Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cerebral Cortex 10, 318–325. doi: 10.1093/cercor/10.3.318.
    1. Younger J, Aron A, Parke S, Chatterjee N, Mackey S, 2010. Viewing Pictures of a Romantic Partner Reduces Experimental Pain: Involvement of Neural Reward Systems. PLOS ONE 5, e13309. doi: 10.1371/journal.pone.0013309

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