Up All Night

No Rest for the Roman

As we wrap up our series on Caligula, I want to return to one of his symptoms that I didn’t have time to examine closely in week two: insomnia. Insomnia affects roughly ten percent of the adult population, and is defined as difficulty falling or staying asleep that results in impaired functioning when awake. Insomnia, like many of the other disorders we’ve explored on ULTC, stems from a mix of genetic and environmental factors, such as stress. It’s therefore not surprising that in the midst of the unique challenges facing society in 2020, sleep disturbances are on the rise. “Coronasomnia,” as some people are calling it, has emerged from an increase in anxiety and a disturbance to normal routines, and has public health experts concerned. Sure, we all have a rough night’s sleep every once in a while. But how does this become an everyday occurrence? And what effect does a chronic lack of sleep have on your body during the day?

Don’t let the eyes wide open statue fool you. Caligula battled chronic insomnia. history.com

What Time Is It?

Whether you’re an early bird or a night owl, your body ebbs and flows on a 24-hour cycle called the circadian rhythm. Hormones, digestion, metabolism, body temperature, and more fluctuate throughout the day so that they peak at the right time for optimal sleep and wakefulness. For example, digestion is highest during the day when you’re eating, and lower at night so your sleep is not disturbed because of a bowel movement. 

A nice representation of how the circadian rhythm affects the body throughout the day, keeping in mind that this is different between individuals. Think about moving that important meeting to before lunch! precriptionhope.com

Like any efficient operation, the circadian rhythm requires keeping a tight schedule. Luckily, the brain contains a biological clock. Just above the place where the nerves from the eyes enter the brain, there is a small region of the brain called the suprachiasmatic nucleus (SCN) that makes sure tissues throughout the entire body have their “watches” synchronized, including those brain regions responsible for initiating sleep. The SCN uses a variety of information to set the biological clock, but is especially dependent on light. That’s why you’ve probably been told to avoid phone, computer, and TV screens before bed, as they tend to throw off the body’s internal signal that it’s time to wind down and catch some z’s.

This figure shows the inputs that the SCN receives (light, melatonin) and a variety of ways its signaling can be disrupted (jet lag, light at the wrong times). calories proper.com

The molecular mechanisms that underlie the circadian rhythm were discovered in fruit flies initially, but have also been characterized in mammals. Two key proteins, called CLOCK and BMAL1 work together to turn on genes important for your body to function during the day. They also turn on genes that make proteins called CRY and PER. This creates a negative feedback loop in which CRY and PER work to turn off CLOCK and BMAL1. As a result, by the end of the day, CRY and PER have accumulated enough to suppress CLOCK and BMAL1, and the circadian rhythm moves through its night time phase. Throughout the night, CRY and PER levels decrease because CLOCK and BMAL1 are no longer active to produce them. So by the time the morning rolls around, CLOCK and BMAL1 are no longer inhibited, and the cycle can begin again.

On the top panel, this figure shows how CLOCK and BMAL produces CRY, leading to the inhibition. The bottom graph gives you an idea of how CRY levels fluctuate. They are highest at the beginning of the night, and then decrease by the morning so the cycle can start over. Hirano et al. (2013)

Sleepy Head

Many factors can throw off this remarkable biological cycle, resulting in short-term or chronic sleep disturbances. As many sleep specialists and neurologists seeing patients with “coronasomnia” can attest, stress is one factor that disrupts the circadian rhythm. Some hypothesize that this is because anxiety creates a state of “hyperarousal” in the brain, making it harder to initiate sleep. In addition, stress can disrupt the endocrine system, which provides key input to the SCN, thus throwing off the circadian rhythm.

In addition, changes in routine can alter the circadian rhythm. If you’ve ever experienced jet lag, then you know what happens when the light-dark cycle of your environment doesn’t match up with your internal clock. While global travelers adapt after a couple of days, people who work night shifts may have a harder time rectifying their circadian rhythm, which has been linked to increased risk of depression and alcoholism. 

Some forms of insomnia have been linked to genetics. There are inherited forms of Advanced Sleep Phase Syndrome, where patients go to bed very early and wake very early, that can be caused by mutations in a gene that encodes one of the PER proteins. In addition, there is a fatal form of familial insomnia that can be caused by a mutation in the same protein that causes mad cow disease. This protein accumulates in the thalamus, a key area controlling the sleep-wake cycle that is regulated by the SCN. 

Anyone who has struggled to make it through the day after an all-nighter is familiar with the unpleasant effects of sleep deprivation. When this becomes a chronic issue, the consequences become more serious. Although it’s unclear the direction of the relationship, insomnia is associated with increased risk for depression and exacerbates conditions like hypertension and diabetes. Lack of sleep also impairs motor skills and reaction time, putting insomniacs at increased risk for accidents. A burgeoning area of neuroscience research is how circadian disturbances are linked to neurodegenerative diseases like Alzheimer’s.

If this graphic doesn’t give you the motivation to get your 8 hours tonight, I don’t know what will. postivehealthonline.com

Sleep On It

Clearly, sleep debt has wide-ranging effects, from diet to mood to attention. This makes sense because the circadian clock controlling sleep cycles also regulates a variety of critical biological processes that fluctuate cyclically. It’s easy to imagine how insomnia contributed to Caligula’s mental illness and poor leadership.

With that in mind, I recommend you also catch up on your sleep, because we will be back next week with a brand new series, and you won’t want to miss a moment!


Colten, H. R., & Altevogt, B. M. (2006). Sleep disorders and sleep deprivation: An unmet public health problem.

Fatal Familial Insomnia. (2018, April 20). Retrieved from https://rarediseases.org/rare-diseases/fatal-familial-insomnia/

Karin Brulliard, W. W. (2020, September 03). The pandemic is ruining our sleep. Experts say ‘coronasomnia’ could imperil public health. Retrieved from https://www.washingtonpost.com/health/2020/09/03/coronavirus-sleep-insomnia/

Patke, A., Young, M. W., & Axelrod, S. (2019). Molecular mechanisms and physiological importance of circadian rhythms. Nature Reviews Molecular Cell Biology,21(2), 67-84. doi:10.1038/s41580-019-0179-2

Roth, T. (2019, November 14). Insomnia: Definition, Prevalence, Etiology, and Consequences. Retrieved from https://jcsm.aasm.org/doi/full/10.5664/jcsm.26929

Shiel, W. C., MD. (2018, December 11). Definition of Familial advanced sleep-phase syndrome (FASPS). Retrieved from https://www.medicinenet.com/script/main/art.asp?articlekey=15873

Suni, E. (2020, September 03). What is Circadian Rhythm? Retrieved from https://www.sleepfoundation.org/articles/what-circadian-rhythm

Vitaterna, M. H., Takahashi, J. S., & Turek, F. W. (n.d.). Overview of Circadian Rhythms. NIAAA.

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