Skip to main content

Grief in the Time of COVID-19: What the Neuroscience of Grief Can Tell Us About Adapting to a New Normal

By T. J. Cahanap

This piece is part of a special series of posts by medical student authors who were solicited to speak on the relationship between COVID, medicine, and neuroethics.

Image courtesy of x1klima on Flickr
During this time of global crisis, it has felt like everything has come to a screeching halt. Meetings, family gatherings, and even weddings have moved to the digital conference room. People all around the world have lost their careers, their routines, their sense of normalcy. We are bombarded by an upheaval of routine paired with the uncertainty that comes with learning facts that seem to change by the day.

As the anxiety of the unknown becomes further compounded by the panic from the relentless media coverage, Dr. Sung-Wan Kim of the Chonnam Nation University Medical School in the Republic of Korea emphasizes the need to bolster our psychological resilience. Studies have shown that biopsychosocial interventions like a healthy lifestyle, regular exercise, and a strong connection with community have been associated with a stronger, more robust immune response. In the same vein, a loss of these things that populate the sphere of our personal lives may put us in immunological danger. By implementing forms of psychological support—like telehealth psychiatric interventions and community support groups—we may in fact be harnessing power against the virus.

In order to equip ourselves for the behavioral changes we will see following the mental health crises of COVID-19, we must also consider the latest neuroscience.

A recent article published in Progress in Neuro-Psychopharmacology & Biological Psychiatry outlines the consequences of repeated exposure to uncertainty in rat models, revealing changes in brain dopamine and glutamate signaling that are powerful—the same adaptations produced by repeated exposure to psychostimulant drugs. The investigation showed that repeated intermittent exposure to uncertainty led to sensitization of the locomotor and nucleus accumbens dopamine and glutamate tracts—important in the brain’s reward pathway—in a way that promoted addictive behaviors such as self-administration of amphetamine.

A review examining the effect of uncertainty and stress on human cognitive function identifies a normal distribution of learning efficiency that is mediated by neurotransmission. The review focuses on the permissive effect of glucocorticoids on consolidating activity-dependent plasticity; the peak of this consolidation occurs only when modeled uncertainty is able to be overcome. The ability to consolidate—and thus to learn—succumbs to “toxic stress” when the uncertainty becomes overwhelming.

These consequences on behavior in rats and humans raise powerful questions about what we must be prepared for as we address the neuropsychological changes in our population post-pandemic—what comorbid conditions have we become more susceptible to? Should we approach our new motivated behaviors with this construct of maladaptive brain circuitry in mind?

Image courtesy of Pexels

Furthermore, Intolerance of uncertainty (IU)—or the tendency to respond with negative emotional, cognitive, and behavioral reactions to uncertain situations and events—has also been recognized as an important maintaining factor in several anxiety disorders, including generalized anxiety disorder, obsessive-compulsive disorder, and social phobia. A study published in the International Journal of Psychophysiology investigating the effect of uncertainty on a startle response in human participants has uniquely shown that this intolerance is associated with attenuated aversive response to an uncertain threat and is ultimately mediated by a lack of perceived controllability. Individual differences in the participants’ IU were associated with smaller startle responses when they anticipated temporally uncertain shocks, supporting the body of self-reported data that has shown that those who are intolerant of uncertainty have found ambiguous situations stressful and have difficulty functioning when faced with those challenges—an important construct to consider when approaching the management of anxiety disorders.

But, here we encounter a contradiction. The more we aim to identify particular targets—a specific “uncertainty” gene, a protein that mediates maladaptive behavior in the face of stress, a quantifiable upregulation of neurotransmitter that signals the trajectory of our coping process—the less a biopsychosocial model makes sense. If we aim to reduce all of our human experience to microbiology and molecular physics, must we then assume that the biopsychosocial model is simply a tool we’re using until we can hone in on the pathophysiology that has yet to be uncovered? If this is the case, which interventions should we spend time and effort pursuing as we equip ourselves for the aftermath of COVID-19?

The answer may lie in the element of grief contained within our new normal of uncertainty.

Grief has long been difficult to study in a neurobiological way due to its intense subjectivity but has garnered attention in recent years. As a nearly universal human experience, grief is important to spheres of mental and public health and poses a new-frontier-type challenge in terms of a translational management approach. This concept of the “social neuroscience” of grief has produced conferences and investigations that attempt to look at the neural correlates of grief in the hopes of identifying possible interventional targets.

A recent article exploring grief during the COVID-19 pandemic published in the Journal of Pain and Symptom Management recognizes the different forms of grief we, as a population, face as we navigate this time, and highlight the role that palliative care providers can have in shaping and sharing resources for support. The article focuses on the effects of anticipatory grief, what the authors describe as grief that “results from uncertainty as well as trying to make sense of what’s coming.” With that in mind, should we approach this grief by modulating neurotransmission the way we propose in disorders related to uncertainty?

A study conducted using fMRI to map the brain regions that participate in grief has shown, unsurprisingly, that grief is mediated by a vast, distributed neural network that involves affect processing, mentalizing, episodic memory retrieval, visual imagery, autonomic regulation, not to mention modulation and coordination of all of these functions together.

Specifically, overlapping findings across both human and rat studies reported in a recent grief conference grant have pointed to the involvement of the hypothalamic pituitary adrenal (HPA) axis and the nucleus accumbens brain regions, tying together the ideas of uncertainty and potential targets for resilience training mentioned throughout this discussion. The same regions that underly the mechanisms for maladaptive responses to stress may very well be the ones we must target in our management strategies moving forward.

The HPA axis
Image courtesy of Wikimedia Commons

In viewing our new normal through this lens of grief—a complex, neurobiological phenomenon with intense subjective behavioral consequences—we may be better able to come to terms with the source of our feelings of loss—an inability to say goodbye, the absence of connection, the guilt of survival, the moral distress of resource allocation—and approach them with more appropriate tools. In refocusing our interventions on quality communication, advance care planning, and provider self-care, we may find that our psychological health may be better equipped to handle the uncertainty of tomorrow and carry on with renewed energy.

If our approach to mental health during COVID-19 can be similarly focused on neurobiologically mediating the effects of uncertainty and grief, we may be able to better equip ourselves against the psychological exhaustion we will experience as our days charge forward through the unknown.

The pandemic is frightening for many reasons—we fear for our elderly, our healthcare workers, our careers, our loved ones. But what we really fear is the uncertainty of our future. The things that we felt were unconditional have proven to be susceptible to change after all. We are paralyzed to inaction because we don’t know how to prepare for the unknown.

Here I propose and alternative—to take advantage of the new normal to think in new ways of conceptualizing and treating mental health.  Now is the time to emphasize resilience as a way to proactively combat the continued uncertainty we must face. Resilience—defined by the American Psychological Association as the “process of adapting well in the face of adversity, trauma, tragedy, threats, or significant sources of stress”—seems to be the most powerful tool we have in these challenging times. The neurobiology of resilience is neither a new concept, nor is it simple, but the modifiable factors of resilience may have much to offer us by way of longitudinal, proactive interventions.

Our bodies have natural resilience mechanisms and research has revealed to us that in understanding the neurobiology underlying these, we can build translational approaches on promoting stronger responses to adversity. Cognitive reappraisal techniques have been shown to modify the distress associated with stress by enabling the prefrontal cortex to dampen the hyperarousal that mediates emotions like anxiety and stress. Cognitive control of emotion can be achieved through centrally-directed as well as peripherally-directed interventions like maintaining relationships, keeping physically active, and eating healthy foods, all of which strengthen important neurobiological pathways of resilience: increased norepinephrine release in the locus coeruleus to ventral tegmental pathway, increased neurogenesis and branching in hippocampal neurons, and a decrease in maladaptive glutamatergic transmission in the nucleus accumbens.

As the COVID-19 situation unfolds, the stresses of today have proved to be as unprecedented as the day before with no perceived end in sight. This uncertainty—whether it manifests as a modified career path, a seemingly endless frontline, or an adjustment to new methods of socialization—may have detrimental effects on our neurobiology. It is essential that we revisit our biopsychosocial tools to create management and intervention strategies that not only help us today, but also better prepare us for tomorrow. 


T. J. Cahanap is a rising 3rd year medical student at Sidney Kimmel Medical College who is hoping to pursue a career in neurosurgery. She graduated from the University of Pittsburgh with a B.S. in Neuroscience and a B.A. in the History & Philosophy of Science. She lives in Philadelphia, PA and is currently working on publishing a multimodal creative writing project on the art of studying the brain. 

Want to cite this post?

Cahanap, T. J. (2020). Grief in the Time of COVID-19: What the Neuroscience of Grief Can Tell Us About Adapting to a New Normal. The Neuroethics Blog. Retrieved on , from


Emory Neuroethics on Facebook