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Cambridge University Science Magazine
"A guy goes nuts if he ain't got nobody... I tell ya a guy gets too lonely an' he gets sick." Of Mice and Men, John Steinbeck

The global COVID-19 pandemic has brought new experiences to most of us, introducing extreme changes to our work and social life. Despite social distancing measures being necessary to curb the transmission of COVID-19, the emotional distress caused by social deprivation during lockdown has been tough. Increased loneliness has been reported amongst adults, as virtual alternatives like Zoom or FaceTime are just not the same. Moreover, loneliness has been linked to depression, a health concern officially recognised by the World Health Organization. Poor living conditions and lack of social interaction are associated with poor physical and mental health and higher mortality rates. From an evolutionary perspective, seeking social connections is a deeply-ingrained instinct, essential for survival throughout the animal kingdom. Social contact is associated with an increased life span for various species, such as honeybees, mice, and macaques. When we feel lonely, many of us experience higher levels of anxiety and hypervigilance, a defence mechanism thought to have evolved as a response to potential threats. But why does loneliness have such an effect on the body?

The Neuroscience of Loneliness

The effect of loneliness on the brain is poorly understood from a neuroscientific perspective. Positive social interactions such as smiling faces have been shown to activate neural reward systems. Lack of social interaction, on the other hand, is believed to create a ‘craving for company’ response in the midbrain, comparable to hunger states that trigger the search for food. Several neurotransmitters chemical messengers important for communication between neurons including dopamine, oxytocin, and opioid circuits, are thought to underlie the motivation for social reward. A study led by a research group at the Massachusetts Institute of Technology suggested that a cluster of dopamine-related neurons found in the brainstem region, called the dorsal raphe nucleus (DRN), form part of a neural circuit representing the subjective experience of feeling lonely. The group showed that the DRN area was extremely sensitive to acute periods of social isolation just one day after mice were isolated from their cage companions. In the same study, the group used a technique called optogenetics to switch genetically modified neurons ‘on’ or ‘off’ using light. This increased or suppressed a loneliness-like state, respectively. Activation of DRN neurons increased social preference, making mice more sociable when re-introduced to peers. In primates, negative motivational states have been mainly observed in other areas of the brain, though the role of the DRN itself remains to be properly understood.

The Stress of Social Isolation

While stress is fundamental to survival as it powers the ‘fight-or-flight’ response in dangerous situations, elevated levels of stress can be harmful to both the brain and the body. Stress causes the amygdala, the ‘fear centre’ of our brain, to contribute to the activation of our autonomic nervous system (ANS), alongside our central stress response system known as the hypothalamic-pituitary adrenocortical (HPA) axis. The interactions between the brain and adrenal glands in the HPA axis release cortisol, which helps our bodies deal with acute stress. However, chronic activation of the HPA can wreck havoc on our brains, increasing amygdala activity and causing atrophy in the hippocampus, a brain region responsible for learning and memory formation. Too much stress can remodel our brain by reducing the number of connections between neurons or shrinking the prefrontal cortex, which regulates cognitive functions such as decision making and concentration. These reactions may begin as appropriate responses to a stressful event, but set the stage for more serious conditions including clinical anxiety or major depression, leading to a vicious cycle between stress and mental health. Furthermore, chronic stress induces inflammation in the body, which can contribute to difficulty sleeping, digestive problems, or even a weakened immune system.

A Ruffled Mind Makes a Restless Pillow

The stress from coping with social isolation and survival during the pandemic often reflects in poor sleep. They are tightly linked, as anxiety causes insomnia, which eventually increases anxiety itself. Research suggests lack of sleep contributes to loneliness and is a catalyst for social isolation. Sleep is more important for our brains than we may realise. On average, we spend around one third of our lives asleep. Sleep is essential for good mental and emotional health as well as adequate cognitive function. Restful sleep serves to ‘reset’ brain activity,  to prepare us for emotional challenges the next day. Dreaming during REM sleep helps us process emotional experiences, like a form of nocturnal therapy. In the long term, sleep, including well-placed naps, helps our brain consolidate information and store memories. 

Brain activity after periods of sleep deprivation has been shown to be very similar to that observed in anxiety disorders. Poor sleep puts our brains on guard by triggering spikes in stress hormones early in the morning, and increases activity of the amygdala, which is also crucial for emotional processing and memory consolidation. Sleep deprivation has also been linked to changes within the medial prefrontal cortex and other brain regions associated with emotional control. People who sleep poorly are twice as likely to develop an anxiety disorder and other health problems such as increases in blood pressure, insulin resistance, and body weight. Some of these issues are linked to distinct changes in hunger-regulating hormones associated with sleep deprivation, such as higher levels of appetite-stimulating ghrelin or lower levels of satiety-inducing leptin. Furthermore, sleep restriction modifies our  endocannabinoid levels, chemical signals that affect appetite and our reward system. Therefore, while poor sleep is a common and often underestimated outcome of altered stress levels, it can have other profound physical and psychological effects. 

Coping With Late Night Loneliness

For many, the peak of loneliness comes during the evening or at night. To combat this, smartphones and the Internet have offered an important means of connection during the pandemic. However, late night screen-usage is a disruptive behaviour, affecting not only our body clock but also the levels of melatonin, our ‘sleeping hormone’. Therefore, minimising exposure to bright lights at night can facilitate good sleep. In addition, while a nightcap before bedtime might seem tempting to help quieten the hamster wheel going in your head, it is not a good sleep aid. Alcohol acts as a central nervous system depressant and disrupts sleep, especially in the second half of the night. 

So, what can we do instead to calm our busy minds? Simple activities like reading a good book or just enjoying a cup of tea can help ease your thoughts. Alternatively, mindfulness is a more active way to better cope with pandemic loneliness and related sleeping issues. Mindfulness is like a workout for the brain you practise awareness and concentration, resulting in general calmness and physical relaxation.

While the pandemic has come with many challenges requiring adaptation of our daily lives, it has brought another opportunity to further help destigmatise stress and its related mental health issues, as we are all trying to stay sane in an insane world




Mirlinda Ademi is a third year PhD student in Clinical Neurosciences at Corpus Christi College. Artwork by Zuzanna Stawicka.