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Dissecting Complicated Grief

An empty seat at the dinner table, a final text, a photo faded and worn with time. Reminders of loss manifests in numerous ways, and with that, grief as well. Grief has often been defined as the price we pay for love. Many learn to cope with it–but there still exist a number of people who can’t resolve their grief. Eventually, it transforms into something more intense and debilitating which requires professional treatment, and has become prevalent enough to warrant its own classification.

Complicated grief (CG), now referred to as prolonged grief disorder (PGD), is when lasting symptoms of grief, coupled with interferences in daily functioning and separation distress persist for more than six months after a loss. Surprisingly, this disorder has been the cause of much debate. With how widely it was being documented, whether or not it should be categorized as its own disorder had been disputed for some time before it was finally added to the DSM-5, the standard classification of mental health disorders, in March of 2022.

An extensive range of feelings and physical symptoms are associated with PGD. Many of them align with symptoms of non-complicated grief and major depressive disorder which can make it difficult to differentiate the two. Feeling “stuck”, being unable to function properly on a day-to-day basis, withdrawing from social circles, being unable to find enjoyment or purpose, feeling guilt/remorse, and persistently yearning for the bereaved are some of the common symptoms of PGD. The key to distinguishing PGD from MDD (major depressive disorder) is understanding that in PGD, grief is the primary contributor to the manifestation of these symptoms and negative thoughts/emotions are centered around the bereaved. MDD on the other hand, is not necessarily linked to grief but may succeed it. The thoughts and emotions that accompany it are more global and generalized.

The symptoms described above simply highlight the few ways PGD manifests on a physical and emotional level. Further examination of the effects of PGD on a neurological and biological level reveal fascinating discoveries. In 2020, Dr. Zoe Donaldson, at the University of Colorado-Boulder, conducted a study involving the separation of voles–rodents that mate for life. When a bond between two voles forms, there is a change in the way proteins fold in the part of the reward system known as the nucleus accumbens. As time progresses, there is increased neural activity in that area every time the voles approach each other. When they are separated, stress hormones and, surprisingly, dopamine levels surge to aid in finding that mate and maintaining the bond.

The findings of this study are corroborated by the findings of another done by Dr. Mary-Frances O’Conner and others on gene expression responses to CG (complicated grief) and non-CG (non complicated grief). This study found increased activity of genes involved in dopamine receptor binding in human participants with CG. Dopamine is part of the reward system, which is often associated with the nucleus accumbens–a region of the basal forebrain. Constant reminders of and reminiscing the bereaved may continue to activate neural reward pathways in this region which in turn increases dopamine levels and interferes with natural adaptation to the loss. It is why the voles in Dr. Donaldson’s study try to find their mate after being separated from them. This process can be analogous to drug addiction, where dopamine floods the reward pathway, eliciting pleasurable emotions and leads to the desire for more dopamine surges.

Delving deeper into gene alterations, the study found an upregulation (increased activity) of genes involved in general immunological activation and downregulation of genes involved in B-lymphocyte production–the cells that produce antibodies–in both non-CG and CG participants. However, the two differed in their expression of Type 1 interferon-related transcripts–which are crucial to initiating antiviral responses in cells. Non-CG participants demonstrated upregulation of expression whereas CG participants demonstrated downregulation. Cortisol, the hormone released during stress, induces anti-inflammatory responses when it is at moderate levels and explains why the study revealed upregulation of genes involved in general immunological responses. Continuous amplification of cortisol levels as a result of grieving however can actually weaken the immune system by making it resistant to the high levels and in turn, hindering immune response. These findings explain why those grieving have lower immunity and why it is even lower in those with PGD.

Grief offsets a rewiring of the brain in ways that can cause serious harm in the long run. The rewiring itself and the extent to which it occurs has not been examined fully and has recently piqued the interest of the psychology and research community. The studies that have been conducted focus on grief caused by the death of a loved one. However, this is not the sole cause of grief. Further research into PGD induced by loss unrelated to death may provide further insight into the nature of the disorder. Can PGD manifest in individuals who experience loss unrelated to death, what effects does it have, how does it differ from death-related grief are simply some questions that remain unanswered. Further examination of this relatively new disorder is crucial to developing resources and providing support to the minority of the population that suffer from it.


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