Loss of a loved one is a universal phenomenon. For most people, their grieving is resolved after a period of time, and they are able to restart their lives, albeit with adaptations and adjustments. For some, however, the grief continues and becomes a significant source of impairment, morbidity, and mortality. Such grief, affecting perhaps 7% of those experiencing a loss, has been called traumatic, pathological, prolonged, and most commonly, complicated grief. For a long time it was believed that there was not much that could be done in these cases where the grieving was more prolonged or more severe than usual.

Grief is not a mental disorder, but it may become one.1 Proposed classification and diagnostic criteria have been published by the DSM-5 in section G-06 as Adjustment Disorder Related to Bereavement.2 For at least 12 months following the death of a close relative or friend, the individual experiences on more days than not intense yearning/longing for the deceased, intense sorrow and emotional pain, or preoccupation with the deceased or the circumstances of the death. The person may also display difficulty accepting the death, intense anger over the loss, a diminished sense of self, a feeling that life is empty, or difficulty planning for the future or engaging in activities or relationships. Mourning shows substantial cultural variation; the bereavement reaction must be out of proportion or inconsistent with cultural or religious norms. A search of ClinicalTrials.gov identifies 26 trials of psychosocial, pharmacologic, or multimodal approaches to treatment of symptoms of grief or bereavement.3 Readers should note that complicated grief is not recognized as an indication for labeling of treatment by any regulatory body, and that all such references in the papers contained in this issue should be seen as “off-label.”

With that caveat in mind, we recognize the researchers who have contributed papers to this issue of Dialogues in Clinical Neuroscience. Consistent with the universal experience of complicated grief, the authors come from Asia, Australia, Europe, and North America, and represent a variety of disciplines. Demonstrating the vitality of this area, some of the authors are internationally recognized senior scholars, while others are emerging investigators just launching their research careers. We are grateful for their willing participation and for their important contributions; specifically we want to thank Prof M. Katherine Shear for her guidance on the organization of this volume.

We begin this issue with a State of the art paper by Prof Shear (p 119) whose pioneering work has done so much to stimulate and provoke the field. Prof Shear presents definitions and criteria, and discusses diagnosis, risk factors, and treatment approaches. Importantly, she navigates through the many contentious debates around the nosological considerations involving the “bereavement exclusion” in the diagnosis of Major Depressive Disorder.

Two related and complementary papers in the Translational research section underscore the physiologic risk of complicated grief. The first, from Prof Thomas Buckley and colleagues (p 129), highlights the neuroendocrine, chronobiological, and immune system effects, as well as the hemodynamic and prothrombotic parameters associated with grief and bereavement. The authors argue convincingly for the importance of prospective studies and for the need for preventive interventions. The second paper, from Prof Mary-Frances O’Connor (p 141), presents a theory-based exploration of neuroimmune and brain activation biomarkers in complicated grief. This work has the potential for clarifying a number of complex conceptual and diagnostic issues in establishing the boundaries of mood, anxiety, and stress-related disorders. Her perspective also moves forward our general understanding of the often-observed “broken-heart” phenomenon.

Treatment-oriented approaches begin the Clinical Research section of the issue. In the first paper, Drs Eric Bui, Mireya Nadal-Vicens, and Prof Naomi Simon (p 149) review the evidence on use of pharmacologic agents, alone or in combination with psychotherapeutic interventions, for treatment of complicated grief. From a very limited database, consisting of open trials and relatively small-scale controlled studies they conclude that there are both pharmacologic and neurobiological rationales for further studies with a broader range of treatment options. They offer the suggestion that pharmacologic intervention might serve to make psychotherapies more efficacious. Prof Julie Wetherell (p 159) continues this section by presenting a specific psychosocial intervention for complicated grief. She discusses an attachment theory-based approach to psychotherapy, complicated grief therapy (CGT). She describes the roots of this new approach in cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT). CGT is an important addition to the therapeutic armamentarium, and Prof Wetherell presents us with all the essentials necessary for application of this approach and provides an engaging case example of Ann, a 52-year-old in the fourth year of mourning for her deceased husband.

Much of the research in complicated grief has been concerned with clinical issues, particularly within particular segments of the population, and the Clinical research section continues with articles on this theme. In the next paper, Prof Andreas Maercker and Dr John Lalor (p 167) raise the provocative diagnostic question of whether it is possible to differentiate normal from abnormal when it comes to grief, they then show how an understanding of post-traumatic stress disorder (PTSD) informs the approach to prolonged or complicated grief, and they move on to review treatment options. They highlight the interesting potential of Web-based interventions. In the next paper, Dr Ilanit Tal Young and a group of colleagues under the leadership of Prof Sidney Zisook (p 177) describe the specific issues related to complicated grief following a death by suicide. Death by suicide is far from rare. In the US, suicide is now one of the top 10 leading causes of death, and almost everyone knows someone who has died by suicide. That notwithstanding, the authors identify some special issues around suicide death: stigma, self blame, guilt, and feelings of responsibility among them. Rates of complicated grief are estimated to be as much as 4 times higher than that experienced by the general bereaved population. Treatment studies are just beginning in this area, and the authors point to the pressing need to develop meaningful approaches both to reduce suicide risk and to assist those experiencing the wrenching effects of the suicide of a loved one. In the following paper Prof Anette Kersting and Dr Birgit Wagner (p 187) address issues of complicated grief among those who have experienced death of an infant. They describe the very high rates of complicated grief following termination due to fetal abnormality and discuss the very different issues presented by mothers and fathers after prenatal loss. Despite the very high risk for complicated grief and other mental health sequellae, the authors identify the severely limited availability of effective clinical follow-up. The authors conclude with a call for further research and for controlled trials focusing on high-risk subgroups and on parents suffering from the loss of a child. Death is a part of the everyday experience of older people, and in the next paper Prof Mark Miller (p 195) describes special considerations related to complicated grief in those suffering losses of spouse, siblings, peers, and, less commonly, of adult children and grandchildren. Complicated grief may be exacerbated by medical burden, cognitive impairment, and need for functional assistance. All of these may combine to result in the need to change residence following death. Such change could mean moving to a congregate residential facility or relocating to be closer to family members. Through use of an informative case vignette Prof Miller captures the special challenges of diagnosis and treatment of complicated grief in older people.

The issue concludes with two Brief reports. The first, from a group of colleagues led by Prof James Bolton (p 204) highlights the importance of culture in approaching considerations of complicated grief. Their work, with the Aboriginal or First Nation populations of Canada is a model of the organization of the many professional perspectives necessary in a comprehensive public health oriented approach. It should be noted that this work is carried out within a strong commitment to what has been called community-based participatory research (CBPR).4 The final paper is from Dr Satomi Nakjima and colleagues (p 210) and deals with complicated grief following violent death of a loved one. The paper, in preparation prior to the earthquake, tsunami, and radiation that occurred on March 11, 2011, reflects the reality and relevance of the topic of this issue. Dr Nakajima was a member of the Disaster Support Team of the Japan National Institute of Mental Health and was able to put into practice many of the principles of diagnosis and treatment outlined in this article. We at Dialogues in Clinical Neuroscience salute Dr Nakajima and her colleagues and wish them well in these unimaginable circumstances.

Barry D. Lebowitz, PhD; Dieter Naber, MD

REFERENCES
 1. Pies R. Available at: http://psychcentral.com/blog/archives/2008/10/04/ is-grief-a-mental-disorder-no-but-it-may-become-one/all/1/ accessed February 4, 2012.
 2. DSM-5. Available at: http://www.dsm5.org/proposedrevision/pages/ proposedrevision.aspx?rid=367 accessed February 4, 2012.
 3. Available at: http://clinicaltrials.gov/ct2/results?term=&recr=&rslt= &type=&cond=grief&intr=&outc=&lead=&spons=&id=&state1=&cntry1= &state2=&cntry2=&state3=&cntry3=&locn=&gndr=&rcv_s=&rcv_e=&lup_s= &lup_e= Accessed February 4, 2012.
 4. Viswanathan M, Ammerman A, Eng E, et al. Community-Based Participatory Research: Assessing the Evidence. Rockville, MD: Agency for Healthcare Research and Quality; July 2004. Publication 04-E022-2.