Circadian Rhythm

A circadian rhythm is a natural process that regulates physiological and behavioral changes. The term circadian comes from the Latin phrase “circa diem,” which means “around a day.” The circadian rhythm is 24 hours in the human body and is commonly referred to as the body’s biological clock.  

One of the most essential and well-known circadian rhythms is the sleep-wake cycle. Humans' sleep-wake cycle responds to environmental cues of light and darkness and synchronizes cellular activities with the solar day. It does this by stimulating the suprachiasmatic nucleus, a small group of nerves in the hypothalamus which is an autonomic control center of the brain, to release hormones such as serotonin, when the retina in the eye is exposed to sunlight.  

Circadian rhythms are essential because they actively drive wakefulness. Humans have a natural homeostatic sleep drive that accumulates during wakefulness and promotes sleep initiation. After falling asleep, this sleep drive rapidly diminishes. When functioning correctly, the circadian system decreases alertness during the night, especially in the latter half of the night, helping to maintain sleep until it’s time to awaken. Alterations in the circadian timing system and desynchrony with desired sleep-wake times can result in sleep-wake rhythm disorders and other chronic health conditions such as obesity, diabetes, bipolar disorder, depression, and seasonal affective disorder. 

Additionally, circadian rhythms regulate physiological systems, including daily rhythms in core body temperature, melatonin secretion, cortisol, and appetite. For example, saliva volume is greater during the day than at night to aid in digestion. Additionally, gastric emptying rates are longer in the evening than in the morning, and colonic activity, which propels food through the digestive system, is minimal during sleep. Bile acids are also under circadian regulation to synchronize with feeding and fasting periods. Circadian regulation also plays a significant role in liver metabolism. On top of that, maintenance of plasma glucose and regulation of lipids, including triglycerides, cholesterol, and free fatty acids, follow circadian rhythms.  

Circadian rhythms work under the control of the suprachiasmatic nucleus, a region in the brain's hypothalamus that controls the production of melatonin, a sleep-promoting hormone. The suprachiasmatic nucleus receives information about incoming light from the retina via the optic nerve, which then relays information from the eye to various locations in the brain, including the pineal gland, a small endocrine gland in the middle of the brain.  

In the presence of light, axons from retinal ganglion cells deliver signals to the optic nerve that activate the suprachiasmatic nucleus to release an inhibitory neurotransmitter, gamma-amino-butyric acid (GABA). GABA inhibits the paraventricular nucleus of the hypothalamus, ultimately inhibiting the pineal gland, and preventing melatonin production.   

In contrast, as night approaches and there’s less light, retinal ganglion cells inhibit the suprachiasmatic nucleus, which leads to activation of the paraventricular nucleus and the pineal gland produces more melatonin, thereby promoting sleep.  

Typically, light exposure at the end of the typical sleep period moves the circadian rhythm earlier and helps to wake up an individual. Conversely, light in the evening and first half of the usual sleep period postpones the circadian rhythm, thereby keeping the individual awake. Furthermore, specific genes are involved in the production of circadian rhythms, including PERIOD, CRYPTOCHROME, CLOCK, and BMAL1, which are expressed in the suprachiasmatic nucleus during the day and activate feelings of wakefulness and alertness.  

Circadian rhythms can be disrupted by an intrinsic malfunction in the circadian timing system. Intrinsic disorders include delayed sleep-wake phase disorder, advanced sleep-wake phase disorder, non-24-hour sleep-wake rhythm disorder, and irregular sleep-wake rhythm disorder.   

The underlying cause of delayed sleep-wake phase disorder is unknown; however, it’s characterized by delayed bedtimes and wake times compared to conventional or desired times. This results in chronic sleep insufficiency and daytime impairment. It most often begins in adolescence and is accompanied by depression.  

Advanced sleep-wake phase disorder is genetically inherited in an autosomal dominant, highly penetrant pattern where only one copy of the gene has to be passed down for the next generation to be affected. It occurs with increased age and results in the weakening of circadian rhythms and environmental cues.  

Non-24-hour sleep-wake rhythm disorder typically affects those who are blind. Without light cues, the circadian system fails to maintain a stable alignment and functions on a circadian period longer than 24 hours.  

Lastly, irregular sleep-wake rhythm disorder is commonly seen in those with dementia, with a loss of modulation from the circadian system on sleep and wakefulness.  

Circadian rhythms can also be disrupted by extrinsic factors, such as air travel (i.e., jet lag) or shift work, which require individuals to be awake at times that are out of sync with their intrinsic rhythms. Additionally, retinal circadian photoreceptors are maximally sensitive to blue light emitted from devices such as tablets and cell phones. Depending on individual traits, including age, gender, and genetic background, some individuals may be more susceptible to sleep disruption by blue light.  

A disrupted circadian rhythm can be reset by various methods based on the underlying cause. Intrinsic disorders can generally be treated with behavioral modifications, including advancing bedtimes and rise times to a schedule that aligns with one’s social and occupational requirements; avoiding poor sleep habits; minimizing or eliminating caffeine, nicotine, and alcohol; and avoiding daytime naps. Additionally, one may refrain from stimulating activity, such as working or watching television, for at least 2 hours before the desired sleep onset time. One can also avoid blue light-emitting devices for several hours before bedtime. If refractory to behavioral changes, melatonin and light therapy can be used to help realign the circadian rhythm.   

Treatment for secondary circadian rhythm sleep disorders, such as jet lag, involves aligning the individual’s internal circadian phase with the new light-dark cycle in the destination time zone. This adjustment can occur naturally without treatment, or strategic use of light and melatonin can help with the process. Light therapy can be in the form of natural outdoor daylight or a lightbox. Melatonin can be taken on the evening of arrival and continues for up to 5 days. For jet lag and shift work disorder, caffeine and short naps less than 30 minutes at least 8 hours before bedtime may also promote alertness without disrupting nighttime sleep. Lastly, if necessary, medications such as benzodiazepines (e.g., temazepam, midazolam, and triazolam) and non-benzodiazepine benzodiazepine receptor agonists (e.g., zolpidem and zopiclone) can be prescribed by a healthcare professional.