The psychopathological characteristics of prolonged grief

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Summary of The psychopathological characteristics of prolonged grief

341 Modern psychopathologies or old diagnoses? Journal of Psychopathology 2015;21:341-347 Summary Grief is a normal human response to the death of a loved one that may vary among individuals and in the way it manifests itself across cultures. Whereas the majority of bereaved people adjust adequately to the loss, a small but noteworthy proportion of individuals may experience a prolongation of the symptoms of acute grief well beyond the period when these have com- monly abated. This syndrome, characterised by prolonged psy- chological distress in relation to bereavement, has been termed prolonged grief (PG) and shows distinct psychopathological features compared with other stress-related mental disorders. Accurately diagnosing PG in the context of difficult bereave- ment is an ongoing challenge to clinicians and researchers and many have called for improving the identification of PG and its treatment. PG has been recognised as a predictor of negative outcomes, such as substantial impairment in work and social functioning, reduction of quality of life, risk for mental disor- ders and suicidality, and physical health problems. This article discusses the main clinical features of PG, the determinants as- sociated with the severity of PG symptoms, the risk factors that may predispose an individual to develop PG and the efficacy of different preventive and treatment approaches, including psy- chopharmacological and psychotherapeutic interventions. Key words Bereavement • Grief • Complicated grief • Traumatic grief • Prolonged grief disorder • Prolonged grief diagnostic criteria • Prolonged grief risk factors • Prolonged grief treatment The psychopathological characteristics of prolonged grief M.G. Nanni1, S. Tosato2, L. Grassi1, M. Ruggeri2, H.G. Prigerson3 1 Institute of Psychiatry, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Italy and University Hospital Psychiatry Unit, Program in Psycho-Oncology and Psychiatry in Palliative Care, S. Anna University Hospital and Local Health Agencies, Ferrara, Italy; 2 Section of Psychiatry, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy; 3 Joan and Sanford I, Weill Department of Medicine, Weill Cornell Medical College, Cornell University, New York, USA, and Center for Research on End of Life Care, Weill Cornell Medical College, Cornell University, New York, USA Correspondence Maria Giulia Nanni, Institute of Psychiatry, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, corso Giovecca 203, 44121 Ferrara, Italy • E-mail: [email protected] Introduction Over the last 20 years, several studies have focused on complications of grief and bereavement 1 2. Assuming that bereavement is a normal human experience and that grief is the physiological reaction to the loss of a loved one, many researchers have attempted to identify the stages of grieving process as well as the order in which they may arise. Historically, Kübler Ross described grief as a succession of five steps according to a relatively linear “recovery” trajectory over time (the so-called five-stage model) 3. Recently, it has been showed that bereaved peo- ple, in correlation with different individual and contex- tual features, may experience a range of symptoms during the whole process, and not necessarily in a sequential or- der 4. Empirical data have indeed supported the existence of distinct patterns of grieving, allowing recognition and study of different trajectories of the process 5 6. Evidence has demonstrated that most bereaved individu- als finally succeed in coming to terms with the loss of their loved one and integrate this experience in their lives 1 4 5. The time period during which this process is completed has not been definitely established, but most experts agree that progress usually becomes apparent by 6 months. Even if possible intense symptoms may re- emerge periodically, most people are able to adjust to the loss by this time 7-10. Unfortunately, a small subset of bereaved individuals never fully integrates the loss into their life, and continue to experience severe disruption in daily life even many years after the loss. The labels given to this condition have changed over the years, including pathological grief, traumatic grief, com- plicated grief and, more recently, prolonged grief 10. We decided to use the term “prolonged grief” (PG) for two reasons. First, it better expresses the nature of the disorder, characterised by the abnormal persistence of severe disa- bling symptoms related to the bereavement 11. Second, it is most likely that the revision of the International Clas- sification of Disease (ICD-11), which is currently planned for approval by the World Health Assembly, will intro- duce a new diagnosis to recognise this clinical condition, using the label of Prolonged Grief Disorder (PGD) 12. However, the identification of this syndrome in the cur- rent psychiatric diagnostic systems has been much de- bated recently. Factor analytic studies have identified and isolated the specific PGD symptoms, indicating that it is 342 M.G. Nanni et al. tifying bereaved individuals who suffer from the syn- drome and provide them with appropriate, timely and effective treatments. The phenomenology of prolonged grief According to the model proposed by Prigerson et al. 13, PG includes two core clusters of symptoms: the first is related to separation distress (e.g. intensive yearning, strong desire of the beloved, constant state of concern linked to the memory of the loved one), and the second is related to traumatic distress (e.g. recurrent and intru- sive thoughts about the absence of the deceased, sense of disbelief regarding the death, being angry or emotionally numb, tendency to avoidance of memories associated with the pain of loss) 10. Bereaved people who suffer from PG typically have difficulty in accepting the reality of the death and in adapting to life without the deceased. They find themselves in a repetitive loop of intense yearning and longing, being unable to move forward in life. PG symptoms last over 6 months, can sometimes persist for years and negatively influence functioning and quality of life 14. PG symptoms also include anger, guilt, or blame regarding the death, lowered self-worth, inability to form new bonds or relationship with others and strong denial of the loss, which is accompanied by feelings of mistrust, bitterness and identity confusion 10 29. Overall, a signifi- cant preoccupation with the deceased is developed, with ruminations about circumstances or consequences of the loss, intense physical or emotional reactivity to remind- ers, avoidance of reminders, or compulsive proximity seeking (e.g., keeping reminders of the died person). This condition can lead bereaved individuals to be chronically disengaged from others and from the world, to believe that life is empty and meaningless without the deceased and that their intense pain will never end. For this reason, suicidal thoughts may occur and are usually related to the hope of being reunited with the deceased loved one 8 30. Some years ago, a panel of experts on bereavement ap- proved a consensus list of shared symptoms, outlining the clinical features of PG. They proposed empirically a final diagnostic criteria set: bereaved individuals with PGD must experience yearning (i.e. physical or emotional suf- fering due to an intrusive unfulfilled desire for reunion with the deceased) and at least five of nine additional symptoms. The latter must persist for at least 6 months after the bereavement and be associated with functional impairment 10. Factor analysis studies have contributed to define the nature of PG and underlined its clinical mean- ingful dimensions. In a large sample of patients, using the 19-item Inventory of Complicated Grief, six clusters of symptoms were identified: “yearning and preoccupa- tion for the deceased”, “anger and bitterness”, “shock distinct from other psychiatric disorders, such as anxiety, depression, post-traumatic stress disorder and adult sepa- ration anxiety 13-16. Based on these data, consensus criteria for PGD have been formulated 10. Nevertheless, the Diag- nostic and Statistical Manual of Mental Disorders, 5th Edi- tion (DSM-5), failed to include this diagnosis, relegating the complications of grief to the section “other specified trauma and stressor-related disorders”, under the label of Persistent Complex Bereavement Disorder (PCBD), with the explicit criteria listed under conditions requiring fur- ther study 17. The DSM-5 reluctance to recognise PGD as a full diagnosis is probably due to different reasons, such as the risk to pathologise normal grief responses, the risk to underestimate the influence of cultural and contextual variables on the variation of the manifestations of grief and the risk to place much emphasis on traumatic stress, which may result in misdiagnosing or not diagnosing in- dividuals suffering from other common and severe men- tal disorders 12 18 19. Contrary to DSM-5, the ICD-11 will likely include, with- in the proposed new group of “Disorders specifically associated with stress”, a separate diagnosis of PGD, as a condition characterised by a distinct psychopathol- ogy 12. The ICD Working Group has exposed different elements favouring the inclusion of this new diagnosis. First, studies have shown that the core symptoms of PG are distinguishable from symptoms of uncomplicated grief 13 20 and are associated with significant conse- quences. In fact, PG can predict long-term functioning impairments, reduction of quality of life, risk for men- tal disorders and suicidality, as well as physical health problems (e.g. hypertension, cardiovascular disorders, immunological dysfunctions) 9 14. Second, the risk of medicalisation of some non-pathological reactions of grief seems very limited: epidemiological data show that a PG diagnosis only applies to a minority (about 10% following normal circumstances of loss) of bereaved people who experience persistent impairment 10 21, with higher rates following disasters, violent deaths, or the death of a child 22-24. Moreover, population rates of PG are estimated between 2.4% and 4.8% 25 26. Finally, di- agnostic requirements have been also drawn carefully taking into account the marked cultural variations in the manifestation of grief. Although more research is need- ed in this area, some studies have shown that PG is pre- sent across a range of cultures, including non-Western settings, as well as across the life span 22 27 28. Controversies aside, a growing literature has outlined PGD as a nosological distinct entity, characterised by distinctive phenomenology, risk factors, aetiology, dif- ferent response to treatment and adverse outcomes 10 29. In this paper, we aim to clarify psychopathological char- acteristics of PG in order to facilitate clinicians in iden- 343 The psychopathological characteristics of prolonged grief whereas depression guilt is usually pervasive and multi- faceted 19. In addition, suicidal thoughts are different: in PG they are most commonly based on the strong desire to reunite with the loved one, whereas depressed people tend to attribute them to pervasive hopelessness 19. Moreover, the two conditions are different in clinical cor- relates. In fact, some evidence suggests that PG is not as- sociated with a change in electroencephalographic (EEG) sleep physiology seen in MDD 36. In a more recent study, it has been demonstrated that bereaved PGD patients present activation of dopamine circuits and reward-relat- ed neural activity in the nucleus accumbens in response to reminders of the deceased, while depressed ones have a reduced capacity of activation of the same pathways 37. How to distinguish PGD from PTSD Experiencing the death of a loved one may be a trau- matic life-changing event. Both related to this severely distressing identifiable event, PGD and PTSD share some similarities, such as symptoms of emotional numbing, disruptive intrusive thoughts, avoidance, inability to func- tion and difficult reintegration into society 19 29 38. How- ever, several studies have shown that most individuals with PGD do not meet criteria for PTSD 31 33 39 40. In fact, phenomenological differences between the two disorders have been detected. First, the hallmark of PTSD is fear, while the dominant emotions associated with PG are yearning and sense of emptiness 29 30. Even when PTSD arises after a loss of a loved one, intrusive thoughts are fixated on the death event itself, whereas in PG bereaved individuals experience intrusive and voluntary thoughts about diverse aspects of the relationship with the de- ceased. Indeed, they do not show typical symptoms, such as flashbacks, nightmares, vivid intrusive recollections of the event 5. Although both disorders are characterised by memories that are maintained permanently over time, the emotional valence of the contents is different: negative for PTSD and bittersweet (negative and positive, often concurrently: the memories of the deceased may pro- vide comfort, but can also stimulate pain as a reminder of what is lost) for PGD 30. In PTSD, the traumatic event generates a sense of threat and leads individuals to avoid internal and external reminders of the death, whereas in PGD avoidance is consequently limited to those stimu- li that serve as reminders of the reality or permanence of the loss. Moreover, hyperarousal symptoms in PTSD are frequent and are related to hypervigilance to threat, whereas in PGD they are rare and related to the loss of interpersonal regulators 19. Sometimes the differences between PTSD and PGD may appear less evident, for example when the deceased one is a child or a victim of major disasters. In these cases, the feelings of injustice and anger over the cir- and disbelief”, “estrangement from other”, “hallucina- tions of the deceased” and “behaviour change, including avoidance and proximity seeking” 19. These factors did not perfectly align with those reported in a subsequent study, which examined the factor structure of PG using the 31-item Structured Clinical Interview for Complicated Grief and found five explanatory factors: “yearning and emotional pain”, “difficulty accepting the death”, “emo- tional numbness, loneliness and social disconnection”, “suicidal ideation and meaninglessness”, “avoidance and negative affect” 17. Although direct comparison is ham- pered by methodological differences, including the quite high rates of comorbidity with other mental disorders, the findings of the two studies have some overlap. We note, for example, that in both cases yearning is indicated as first factor, confirming the centrality of this element in the disorder. The factor analysis studies, integrating clinical insights with empirical data, have contributed to determining the constitutive symptoms of PGD, delineat- ing it as a mental disorder that is distinguishable from other mental disorders such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) 13 15 31. However, some PGD symptoms do overlap with some symptoms of MDD and PTSD, and comorbidity of PGD with MDD is not uncommon 32 33. Indeed, 50-60% of PG individuals also meet criteria for a major depressive epi- sode 26 32. Likewise, some evidence has shown that pre- existing depression may predispose individuals to devel- op PG after the loss of a beloved one 6. Therefore, it may be difficult for clinicians to make a diagnostic distinction between these clinical conditions. How to distinguish PGD from MDD PGD and MDD both include symptoms such as sadness, crying, sleep disturbance and suicidal thoughts. How- ever, several studies have shown important differences between the two disorders. First, they have a different ae- tiology. Whereas PGD specifically arises as a result of a loved one death, MDD can result from many causes and, in some cases, may even arise without a clear cause 5 19. Regarding symptomatology, PGD symptoms are more stable over time than MDD ones. Bereaved individuals with PGD experience a consistent yearning, while MDD does not typically involve yearning. Factor analysis stud- ies have confirmed that yearning loads highly on a grief factor, but not on depression. On the contrary, sadness loads highly only on a MDD factor 13 34. A study on nega- tive cognition among bereaved people have found that “being overwhelmed by the loss” is specific for PGD, but not for depression, and that they show loss-related avoid- ant behaviours, while MDD is characterised by a more global avoidance 35. Likewise, PGD may include feel- ings of survivor guilt, which is specifically death-related, 344 M.G. Nanni et al. Although the nature of the relationship is the most im- portant variable for developing PG, the circumstances of the death can also play a role. Studies have confirmed that traumatic features of the death (e.g. sudden, violent, unexpected death), a lack of preparation, or difficult in- teractions with medical or other staff at the time of the death may predispose to PG 4 10. Loss of a child is also recognised as a powerful risk factor for PG 52. A higher risk of PG is found in cancer patients’ caregivers who report a perceived general disapproval from others, longer duration of caregiving, and own medical disease history 44 53. In a prospective longitudinal study with 342 cancer patients’ caregivers, hospital deaths were asso- ciated with a heightened risk for PGD (21.6% vs 5.2% p = 0.02) compared with home hospice deaths, which may instead have a reduced risk 44. Another important factor associated with PG is a previous psychiatric history of depression, anxiety or bipolar disor- der, as well as a history of multiple trauma or losses 47 54. On the contrary, several investigators have found that spiritual belief systems may decrease the risk of developing PG 55. Regarding ethnicity, a small cohort study has reported in- teresting results: African Americans have a 2.5 times higher incidence of PGD than the Caucasian population 27. Fur- ther research is, however, needed on this issue. Some recent studies have pointed out that psychomet- ric scales, developed for the evaluation of symptoms of PG in the period preceding the death of their loved one, can be useful in predicting subjects at higher risk of post- loss PG. For example, in a palliative care setting, a higher score at the Complicated Grief Inventory (CGI pre-loss) was significantly associated with a PG diagnosis after the loss 56. Similarly, the Prolonged Grief-13 (PG-13), a vali- dated risk assessment screening measure for PG, was use- ful in identifying people at high, moderate or low risk of developing PG after the death of their beloved 57. These data may have important clinical implications, prospect- ing the possibility to detect the population at risk for PG and to offer them interventions as early as possible. The treatment of prolonged grief Several studies have demonstrated that PG has a different course and response to treatment compared with normal grief and depression. Despite this, pharmacological trials in PG are scarce. Historically, the prescription of tricyclic antidepressants to bereaved individuals have been shown to be useful to improve depressive symptoms, but ap- peared less effective than placebo in ameliorating specific PG symptoms 58 59. More recent studies have indicated that dopamine reuptake inhibitors may induce only a moderate response 45, whereas selective serotonin reuptake inhibitors have shown significant improvements on PG symptoms 10 cumstances of the death may be overwhelming, leading to a more severe grief and psychopathological status 30. However, a recent study conducted on 643 survivors from the Asian tsunami has confirmed that PGD is dis- tinguishable from PTSD. In details, bereaved individuals with PGD have obtained significantly lower scores on avoidance, hyperarousal and intrusion at the Impact of Events Scale-Revised, compared to those who were ex- periencing PTSD symptoms 22. Risk factors of prolonged grief Several studies have focused on possible risk factors for PGD 41-43. In a multicentre US study, 19 possible risk fac- tors were evaluated by administering the Bereavement Risk Questionnaire to 262 hospice coordinators. Profes- sionals identified bereavement risk factors, such as per- ceived lack of caregiver social support (70%), caregiver history of drug/alcohol abuse (68%), caregiver poor cop- ing skills (68%), caregiver history of mental illness (67%) and patient is a child (63%) 41. More recent studies have confirmed a specific role of these determinants, and have identified other factors that may predispose an individual to develop PGD, such as female gender, low education, older age, low socioeconomic status and low social sup- port both before and after the death 43 44. Research has also focused on the types of the relationship to the deceased, underlining that attachment issues are salient in creating a vulnerability to PG. There is a substan- tial evidence that individuals with PG have experienced a close kinship relationship with the deceased. The reason why the loss is particularly devastating is harbouring pre- cisely to the perception that the relationship was satisfy- ing, life affirming and identity-defining 45. Examining the correlation between marital quality and adjustment to the impending loss of a terminally ill spouse, it was suggested that security-increasing marriages and insecure attach- ment styles put spouses at risk for elevated prolonged grief symptoms 46. Moreover, emotional dependency on the dy- ing patient was found associated with grief, but not with depressive symptoms 47. In the Japanese general popula- tion, alexithymia has been shown to contribute strongly to depression, but not to PG 48. On the contrary, childhood separation anxiety was significantly present in the history of those who develop PG, but not in other disorders, such as MDD, PTSD or generalised anxiety disorder (GAD) 49. Regarding avoidant attachment styles, contradictory re- sults have emerged: some authors have pointed out a positive association between neuroticism, anxiety and avoidant attachment with PGD severity 50, while others have shown data supporting the thesis that avoidant at- tachment, if associated with low anxiety levels, may pro- mote a marked reduction of PG symptoms 51. 345 The psychopathological characteristics of prolonged grief Conclusions Experts in the field of bereavement agree in recognising PGD as a new diagnostic entity to be included in current psychiatric diagnostic manuals. PGD is in fact character- ised by distinctive phenomenology, aetiology, risk factors, response to treatment and adverse outcomes. The current literature reveals significant advancements in research regarding this condition with important clinical implica- tions. Healthcare professionals may favour early identi- fication of the subset of individuals at risk for PGD, thus reducing the psychological impact of modifiable risk fac- tors and providing them with an adequate psychosocial support. Furthermore, agreement on standardised criteria for PGD will allow clinicians and researchers to identify bereaved individuals who have developed PGD, direct- ing them to specific treatments and preventing negative consequences. The need for further studies, especially double blind, randomised, placebo-controlled trials, is urgently needed in order to identify the most effective treatment modalities. References 1 Zhang B, El-Jawahri A, Prigerson HG. Update on bereave- ment research: evidence-based guidelines for the diagnosis and treatment of complicated bereavement. J Palliat Med 2006;9:1188-203. 2 Rosner R. Prolonged grief: setting the research agenda. Eur J of Psychotraumatol 2015; 19:27303. 3 Kübler Ross E, Wessler S, Avioli LV. On death and dying. JAMA 1972;221:174-9. 4 Maciejewski PK, Zhang B, Block SD, et al. An empirical ex- amination of the stage theory of grief resolution. JAMA 2007;297:716-23. 5 Arizmendi BJ, O’Connor MF. What is “normal” in grief? Aust Crit Care 2015;28:58-62. 6 Lotterman JH, Bonanno GA, Galatzer-Levy I. The het- erogeneity of long-term grief reactions. J Affect Disord 2014;167:12-9. 7 Zisook S, Shear K. Grief and bereavement: what psychia- trists need to know. World Psychiatry 2009;8:67-74. 8 Zisook S, Simon NM, Reynolds CF 3rd, et al. Bereavement, complicated grief, and DSM, part 2: complicated grief. J Clin Psychiatry 2010;71:1097-8. 9 Prigerson HG, Bierhals AJ, Kasl SV, et al. Traumatic grief as a risk factor for mental and physical morbidity. Am J Psychia- try 1997;154:616-23. 10 Prigerson HG, Horowitz MJ, Jacobs SC, et al. Prolonged grief disorder: Psychometric validation of criteria proposed for DSM-V and ICD-11. PLoS Med 2009;6:e1000121. 11 Bryant RA. Prolonged Grief. Curr Opin Psychiatry 2014;27:21-6. 12 Maercker A, Brewin CR, Bryant RA, et al. Diagnosis and 60. A significant reduction of the intensity of grief (48% of the mean score at ICG) and of depressive symptoms (51% of the mean score at HDRS rating scale) was found after administration of paroxetine (10-50 mg per day) to a small group of PG individuals 58. In a case-series of four women with a primary diagnosis of PG, Simon et al. found a 76% improvement in grief symptoms at ICG when prescribing 10 mg per day of escitalopram 61. The efficacy of escitalo- pram (10-20 mg/per day) on specific PG symptoms was confirmed in a subsequent trial 62. However, considering the limited pharmacological research trials, the optimal first-line treatment for PG is a therapy-based approach, with medications used as add-on if needed 63. Several preventive intervention programs have been proposed to enhance adaptation to bereavement and reduce grief symptoms in order to prevent complica- tions and mitigate long-term negative consequences of bereavement. Unfortunately, a meta-analysis examin- ing the results of nine randomised controlled trials on preventive interventions to bereaved individuals at risk to develop PG did not show any effectiveness of these interventions 64. This finding was confirmed in a more recent review: the authors have also argued that such in- terventions may even interfere with the “natural” griev- ing process 65. Nevertheless, some interesting data come from a recent study on an Internet-based therapist-as- sisted cognitive-behavioural intervention as a preven- tion measure of PGD in recently bereaved individuals, called Healthy Experiences After Loss (HEAL). This in- tervention was shown to be well-tolerated and effective in reducing the burden of significant pre-clinical PGD. Although further research is needed, the preliminary re- sults look promising 66. Moreover, psychotherapy specifically designed for PGD (named Complicated Grief Therapy - CGT) has been shown to be beneficial 67. This new psychothera- peutic model, drawn from attachment theory and with roots both in interpersonal and cognitive-behavioural therapy, includes a variety of loss- and restoration-fo- cused techniques. It also includes techniques similar to prolonged exposure, which reduce PG severity, by promoting emotional processing of memories of the death 11. Shear et al. compared CGT with standard In- terpersonal Psychotherapy (IPT) in a randomised trial with PG individuals. Higher response rates (51% vs 28%) and faster time to response were detected in the CGT group 68. In a recent replication and extension of the study, these findings were confirmed demonstrating that CGT, compared with IPT, conferred higher symp- tom reduction, faster response rate (70.5% vs 32.0%) and a greater persistence of the results at 6-month fol- low-up (100.0% vs 86.4%) 69. 346 M.G. Nanni et al. dren and adolescents bereaved by sudden parental death. Arch Gen Psychiatry 2011;68:911-9. 29 Craig L. Prolonged grief disorder. Oncol Nurs Forum 2010;37:401-6. 30 Maercker A, Lalor J. Diagnostic and clinical considera- tions in prolonged grief disorder. Dialogues Clin Neurosci 2012;14:167-76. 31 Barnes JB, Dickstein BD, Maguen S, et al. The distinctive- ness of prolonged grief and posttraumatic stress disorder in adults bereaved by the attacks of September 11th. J Affect Disord 2012;136:366-9. 32 Bryant RA. Is pathological grief lasting more than 12 months grief or depression? Curr Opin Psychiatry 2013;26:41-6. 33 Melhem NM, Rosales C, Karageorge J, et al. Comorbidity of axis I disorders in patients with traumatic grief. J Clin Psy- chiatry 2001;62:884-7. 34 Priegerson HG, Bierhals AJ, Kasl SV, et al. Complicated grief as a disorder distinct from bereavement-related de- pression and anxiety: a replication study. Am J Psychiatry 1996;153:1484-6. 35 Boelen PA, van den Bout J, van den Hout MA. Negative cog- nitions and avoidance in emotional problems after bereave- ment: a prospective study. Behav Res Ther 2006;44:1657-72. 36 McDermott OD, Prigerson HG, Reynolds CF 3rd, et al. Sleep in the wake of complicated grief symptoms: an exploratory study. Biol Psychiatry 1997;41:710-6. 37 O’Connor MF, Wellisch DK, Stanton AL, et al. Craving love? Enduring grief activates brain’s reward center. Neuroimage 2008;42:969-72. 38 O’Connor M, Lasgaard M, Shevlin M, et al. A confirmatory factor analysis of combined models of the Harvard Trauma Questionnaire and the Inventory of Complicated Grief-Re- vised: are we measuring complicated grief or posttraumatic stress? J Anxiety Disord 2010;24:672-9. 39 O’Connor M, Nickerson A, Aderka IM, et al. The tempo- ral relationship between change in symptoms of prolonged grief and posttraumatic stress following old age spousal be- reavement. Depress Anxiety 2015;32:335-40. 40 Carmassi C, Shear MK, Massimetti G, et al. Validation of the Italian version Inventory of Complicated Grief (ICG): a study comparing CG patients versus bipolar disorder, PTSD and healthy controls. Compr Psychiatry 2014;55:1322-9. 41 Ellifritt J, Nelson KA, Walsh D. Complicated bereavement: a national survey of potential risk factors. Am J Hosp Palliat Care 2003;20:114-20. 42 Coelho AM, Delalibera MA, Barbosa A. Palliative Care Car- egivers’ grief mediators: a prospective study. Am J Hosp Palliat Care. 2015 Jan 19. pii: 1049909114565660 [Epub ahead of print]. 43 Lai C, Luciani M, Morelli E, et al. Predictive role of differ- ent dimensions of burden for risk of complicated grief in caregivers of terminally ill patients. Am J Hosp Palliat Care 2014;31:189-93. 44 Chiu YW, Huang CT, Yin SM, et al. Determinants of com- classification of disorders specifically associated with stress: proposal for ICD-11. World Psychiatry 2013;12:198-206. 13 Prigerson HG, Frank E, Kasl SV, et al. Complicated grief and bereavement-related depression as distinct disorders: pre- liminary empirical validation in elderly bereaved spouses. Am J Psychiatry 1995;152:22-30. 14 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. 15 Boelen PA. Symptoms of prolonged grief, depression, and adult separation anxiety: distinctiveness and correlates. Psy- chiatry Res 2013;207:68-72. 16 Golden AM, Dalgleish T. Is prolonged grief distinct from bereavement-related posttraumatic stress? Psychiatry Res 2010;178:336-41. 17 Bui E, Mauro C, Robinaugh DJ, et al. The structured clinical interview for complicated grief: reliability, validity, and ex- planatory factor analysis. Depress Anxiety 2015;32:485-92. 18 Bryant RA. Grief as a psychiatric disorder. Br J Psychiatry 2012;201:9-10. 19 Shear MK, Simon N, Wall M, et al. Complicated grief and related bereavement issues for DSM-5. Depress Anxiety 2011;28:103-17. 20 Dillen L, Fontaine JR, Verhofstadt-Denève L. Are normal and complicated grief different constructs? A confirmatory factor analytic test. Clin Psychol Psychother 2008;5:386-95. 21 Rodriguez Villar S, Sànchez Casado M, Prigerson HG, et al. Incidence of prolonged grief disorder in relatives of patients who die during or after admission in Intensive Care Unit. 2012;59:535-41. 22 Raikumar AP, Mohan TS, Tharyan P. Lessons from the 2004 Asian tsunami: nature, prevalence and determinants of pro- longed grief disorder among tsunami survivors in South In- dian coastal villages. Int J Soc Psychiatry 2015;61:645-52. 23 Van Denderen M, de Keijser J, Huisman M, et al. Prevalence and correlates of self-rated Posttraumatic Stress Disorder and Complicated Grief in a community-based sample of homici- dally bereaved individuals. J Interpers Violence 2014 Nov 10 pii: 0886260514555368. [Epub ahead of print]. 24 Meert KL, Shear K, Newth CJ, et al. Follow-up study of com- plicated grief among parents eighteen months after a child’s death in the pediatric intensive care unit. J Palliat Med 2011;14:207-14. 25 Kersting A, Brähler E, Glaesmer H, et al. Prevalence of com- plicated grief in a representative population-based sample. J Affect Disord 2011;131:339-43. 26 Newson RS, Boelen PA, Hek K, et al. The prevalence and characteristics of complicated grief in older adults. J Affect Disord 2011;132:231-8. 27 Goldsmith B, Morrison RS, Vanderwercker LC, et al. Elevat- ed rates of prolonged grief disorder in African Americans. Int J Soc Psychiatry 2015 [Epub ahead of print]. 28 Melhem NM, Porta G, Shamseddeen W, et al. Grief in chil- 347 The psychopathological characteristics of prolonged grief 56 Nanni MG, Biancosino B, Grassi L. Pre-loss symptoms re- lated to risk of complicated grief in caregivers of terminally ill cancer patients. J Affect Disord 2014;160:87-91. 57 Aoun SM, Breen LJ, Howting DA, et al. Who needs bereave- ment support? A population based survey of bereavement risk and support need. PLoS One 2015;10:e0121101. 58 Zygmont M, Prigerson HG, Houck PR, et al. A post hoc comparison of paroxetine and nortriptyline for symptoms of traumatic grief. J Clin Psychiatry 1998;59:241-5. 59 Hensley PL. Treatment of bereavement-related depression and traumatic grief. J Affect Disord 2006;92:117-24. 60 Bui E, Nadal-Vicens M, Simon NM. Pharmacological ap- proaches to the treatment of complicated grief: rationale and a brief review of the literature. Dialogues Clin Neurosci 2012;14:149-57. 61 Simon NM, Thompson EH, Pollack MH, et al. Complicat- ed grief: a case series using escitalopram. Am J Psychiatry 2007;164:1760-1. 62 Hensley PL, Slonimski CK, Uhlenhuth EH, et al. Escitalo- pram: an open-label study of bereavement-related depres- sion and grief. J Affect Disord 2009;113:142-9. 63 Simon NM. Treating complicated grief. JAMA 2013;310:416- 23. 64 Wittouck C, Van Autreve S, De Jaegere E, et al. The pre- vention and treatment of complicated grief: a meta-analysis. Clin Psychol Rev 2011;31:69-78. 65 Schut H, Stroebe MS. Interventions to enhance adaptation to bereavement. J Palliat Med 2005; Suppl 1:S140-7. 66 Litz BT, Scorr Y, Delaney E, et al. A randomized controlled trial of an internet-based therapist-assisted indicated preven- tive intervention for prolonged grief disorder. Behav Res Ther 2014;61:23-34. 67 Wetherell JL. Complicated grief therapy as a new treatment approach. Dialogues Clin Neurosci 2012;14:159-66. 68 Shear K, Frank E, Houck PR, et al. Treatment of complicated grief: a randomized controlled trials. JAMA 2005;293:2601-8. 69 Shear MK, Wang Y, Skritskaya N, et al. Treatment of com- plicated grief in elderly persons: a randomized clinical trial. JAMA 2014;71:1287-95. plicated grief in caregivers who cared for terminal cancer patients. Support Care Cancer 2010;18:1321-7. 45 Zisook S, Irwin SA, Shear MK. Understanding and managing bereavement in palliative care. In: Chichinov HM, Breitbart W, eds. Handbook of Psychiatry in Palliative Medicine. New York: Oxford University Press 2009, pp. 202-19. 46 vanDoorn C, Kasl SV, Beery LC, et al. The influence of mari- tal quality and attachment styles on traumatic grief and de- pressive symptoms. J Nerv Ment Dis 1998;186:566-73. 47 Johnson JG, Zhang B, Greer JA, et al. Parental control, part- ner dependency, and complicated grief among widowed adults in the community. J Nerv Ment Dis 2007;195:26-30. 48 Deno M, Miyashita M, Fujisawa D, et al. The relationships between complicated grief, depression, and alexithymia ac- cording to the seriousness of complicated grief in the Japa- nese general population. J Affect Disord 2011;135:122-7. 49 Pini S, Gesi C, Abelli M, et al. The relationship between adult separation anxiety disorder and complicated grief in a cohort of 454 outpatients with mood and anxiety disorders. J Affect Disord 2012;143:64-8. 50 Boelen PA, Klugkist I. Cognitive behavioural variables medi- ate the associations of neuroticism and attachment insecu- rity with Prolonged Grief Disorder severity. Anxiety Stress Coping 2011;24:291-307. 51 Mancini AD, Robinaugh D, Shear K, et al. Does attachment avoidance help people cope with loss? The moderating ef- fects of relationship quality. J Clin Psychol 2009;65:1127-36. 52 Zetumer S, Young I, Shear MK, et al. The impact of losing a child on the clinical presentation of complicated grief. J Af- fect Disord 2015;170:15-21. 53 Wright AA, Keating NL, Balboni TA, et al. Place of death: correlations with quality of life of patients with cancer and predictors of bereaved caregivers’ mental health. J Clin On- col 2010;28:4457-64. 54 Bruinsma SM, Tiemeier HW, Verkroost-van Heemst J, et al. Risk factors for complicated grief in older adults. J Palliat Med 2015;18:438-46. 55 Becker G, Xander CJ, Blum HE, et al. Do religious or spir- itual beliefs influence bereavement? A systematic review. Palliat Med 2007;21:207-17.