Highlights:
Issue 8 - August 2025
Issue 10B Article 2
The Neurochemistry of Grief
25/12/31
By:
Wu Yu Tong
Edited:
Khanna Ritwik
Tag:
Psychology and Psychiatry
The following article is a featured submission of the Singapore Biology Reporters’ Challenge 2025. It was awarded the Certificate of Merit during the competition.
“Grief is the price we pay for love." - Queen Elizabeth II
On May 25 2019, the World Health Organisation (WHO) released the 11th revision of the International Classification of Diseases (ICD-11), in which prolonged grief disorder (PGD) – a diagnosis characterised by severe, persistent emotional pain – was formally included (WHO, 2025). Surprisingly, an estimated 7-10% of bereaved adults experience PGD, while approximately 5-10% of children and adolescents also suffer from this extended period of grief (Maccalum et al., 2023).
Even in everyday life, it is inevitable for one to confront grief at a certain point in time. Be it the rejection of your application to your dream school or the death of a loved one, all of us have indubitably suffered a similar sense of sadness at some stage of life. To many, this feeling could be described as extremely unpleasant and overwhelming, typically manifesting after a significant loss.
In order to accurately represent the mental turmoil of individuals facing terminal illness, Swiss-American psychiatrist Kübler-Ross famously proposed the five stages of grief: denial, anger, bargaining, depression, and acceptance (Kessler, 2013). While most people are aware of this concept, many have not thought about the neurological and biophysical effects that silently take place during grief. Thus, this article aims to expound a detailed description of the biochemical changes that occur when an individual experiences grief.
Part I: The Ambush of Grief
“To die is nothing; but it is terrible not to live.”
— Les Misérables by Victor Hugo, in the context of one’s emotional vacuum during grief.
When someone experiences grief, a multitude of changes take place within the brain. While one experiences grief, especially right after a loss, the amygdala baseline activity is observed to become hyperactive, making emotions feel overwhelming and difficult to control (Chen et al., 2020). Thus, this could hint towards why some individuals feel intense anxiety during grief and may even have a panic attack. Interestingly, grief also activates responses from the anterior cingulate cortex and insula, which are in charge of pain perception and sensory processing (Arizmendi et al., 2016). As such, this may show that the brain perceives grief as a physical threat, thus increasing emotional response and levels of pain processing.
In summary, we can conclude that during grief, the brain’s emotion-processing capabilities are greatly heightened. Hence, this explains the excruciating emotional pain that many of us feel mentally while experiencing grief.
Part II: Can Grief Physically Hurt You?
“You care so much you feel as though you will bleed to death with the pain of it.” — J.K. Rowling, taken from “Harry Potter and the Order of the Phoenix”
(Image of cortisol releasing mechanism in stress response system)
While many believe that grief is merely a psychological issue, there is strong evidence which suggests that grief could also cause adverse effects in one’s body. In particular, research has shown that there is an evident relationship between the expression of grief and an individual’s HPA axis (hypothalamic-pituitary-adrenal axis), which is responsible for the body’s response to emotional pain (Kaplow et al., 2013). Primarily, when we grieve, the HPA axis secretes an increased level of cortisol, a hormone linked to stress (Mason et al., 2018). Findings have shown that when cortisol levels are too high in one’s system, there would be several negative side effects on one’s physical body, including high blood pressure, muscle weakness, and even a weakened immune system (Cleveland Clinic, 2021). In fact, prolonged exposure to excessive cortisol is known to cause a condition called Cushing’s Syndrome. This may lead to various symptoms like skin ulcers and hypertension (Cleveland Clinic, 2022).
Other than cortisol, grief also causes an increased release of adrenaline into the body. Adrenaline (also known as epinephrine), which is released by the adrenal medulla, is crucial for the “fight-or-flight” response in us. Initially, this surge in adrenaline would cause faster breathing and heightened alertness, which is linked to the extreme and overwhelming anxiety that one feels, as described in Part I (Healthline, 2018). However, this sudden spike of adrenaline may result in a steep decline in energy after a while, causing one to quickly feel fatigued as the adrenal glands become unable to cope with the ongoing demand of adrenaline (Mayo Clinic, 2017). This thus also might explain the stage of depression in Kübler-Ross's model, as one’s overall energy levels would be lowered throughout the day.
Part III: After the Storm…?
“The reality is that you will grieve forever. You will not 'get over' the loss of a loved one… you will learn to live with it.”
– Elisabeth Kübler-Ross, Swiss-American psychiatrist
Fortunately, the brain is proven to be remarkably flexible, whether it be for recovering from physical damage or learning new information. Through a process known as neuroplasticity, the brain can essentially rewire itself after exposure to different stimuli (Puderbaugh et al., 2023). In this case, after one experiences a traumatic experience, the brain can recuperate from this event in the long-term, allowing one to better recover from the emotional turmoil. In particular, the prefrontal cortex would slowly regain its function over the amygdala, allowing one to think more calmly and rationally (Voytek et al., 2010). In addition, the hippocampus, which helps to store memories, has been shown to display strong potential for plasticity, and it can adapt from past trauma such that memories of the loss become more tolerable to a bereaved individual (Leuner et al., 2010).
However, research has also shown that once the damage is done, it is extremely difficult for neuroplasticity to completely bring the brain back to its original state. For example, an individual’s hippocampal volume is shown to decrease after experiencing trauma, implying that memory might become permanently impaired (Bonne et al., 2008). Likewise, cortisol has also been proven to suppress the functions of the immune system, leading to increased inflammation and reduced lymphocytic activity (Morley et al., 2015).
Part IV: Society’s View on Grief
“Grief was the celebration of love; those who could feel real grief were lucky to have loved.” — Chimamanda Ngozi Adichie (Nigerian writer), in Notes on Grief (2021)
From historic to modern times, society’s perception and remedies for grief have changed drastically, and this can be seen through changes in cultures and practices. In Ancient Greece, threnodists would chant poetic laments at gravesides, expressing sorrow for the dead (Lee, 2025).
In modern society, there have also been significant efforts made to recognise grief. Every August 30th, National Grief Awareness Day seeks to encourage conversations about bereavement, providing support to those who have recently suffered from grief (Calendar, 2017).
Part V: Closing Comments
Ultimately, grief is a complex tapestry of psychology, biochemistry, and neurology. While grief is known to be partially affected by our neurological and hormonal response, there are also several factors not covered here, such as societal views and one’s adaptability to grief.
In short, grief is a completely natural response of the body. If one is suffering from extreme grief, it is essential to consult with a trusted friend, adult or medical professional to seek further assistance.
Editor’s note: While widely known, the Kübler-Ross model of grief, which presents a rigid description of how grief progresses over time, lacks sufficient empirical evidence and a solid theoretical underpinning. Nowadays, most bereavement researchers cite George Bonanno’s model of the four trajectories of grief as a foundational paradigm for current research. He describes grief as a process with multiple pathways rather than a one-way street, with the primary four routes being chronic grief, delayed grief, resilience and recovery. One of Bonanno’s most significant findings is the idea of resilience: most people are capable of remaining resolute and overcoming their pain after a profound loss. According to him, grief is not just a negative sensation; it also helps us bolster interpersonal connections and appreciate life through a more meaningful perspective.
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