Circadian rhythm, its disorders and ill-effects of its disruption
Circadian rhythm can be defined as a roughly twenty four hour cycle in the physiological processes of living beings, including plants, animals, fungi and some bacteria. It is endogenously generated but is modulated by external factors like sunlight and temperature. Circadian rhythm is associated with certain patterns of brain wave activity, hormone production, cell regeneration and other biological activities. It is also referred to as internal body clock. Many consider it to be a single process but, in fact, it is a number of body clocks running throughout the day. For instance, the mental alertness is at peak at 9AM and 9 PM and the physical strength is at peak at 11 AM and 7 PM in a day. Circadian rhythm gradually gets established during the first months of life.
The suprachiasmatic nucleus, a part of the hypothalamus that lies at the base of the brain near pituitary gland, is the location of the internal body clock since it responds to light and dark signals. In the mornings, with exposure to light, the suprachiasmatic nucleus sends signals to raise body temperature and produce hormones like cortisol. The suprachiasmatic nucleus also responds to light by reducing the release of the hormone - melatonin, which is associated with sleep onset. Melatonin is produced when the eyes signal to the suprachiasmatic nucleus that it is dark. Melatonin levels rise in the evening and stay elevated throughout the night, promoting sleep.
The suprachiasmatic nucleus also regulates appetite, body temperature and other biological states. If somehow or other the suprachiasmatic nucleus is damaged due to some reason, the sleep and wake rhythm disappears. Although the internal body clock is self-regulating, it responds to certain external cues that keep it set for 24 hours.
The following external factors affect it strongly –
Light- It is a very influential factor. When people are exposed to light at intervals that are at odds with the outside light, they unconsciously reset their body clocks to match the times they are exposed to the light. Moreover, 90% of blind persons have disturbances of circadian rhythm.
Melatonin – The cells of the suprachiasmatic nucleus contain receptors of melatonin, which is a hormone produced by the pineal gland located between two hemispheres of the brain. The suprachiasmatic nucleus is, therefore, quickly influenced by the levels of melatonin in the body, which begin to climb after dark and ebb after dawn. Due to its light sensitivity, melatonin regulates the sleep and wake cycle.
Time – Time schedules of different daily activities act as a cognitive pressure to keep the sleep and wake cycle on track.
Circadian rhythm disorders – Some common circadian rhythm disorders are as follows –
Delayed sleep phase disorder – It is most common in adolescents and young adults. It occurs, when sleep onset and wake-up time are delayed in relation to normally accepted sleep schedules i.e. 10 PM to 6 AM. The individuals typically are unable to fall asleep until quite late i.e. 2-6 AM. Once asleep, they get up later in the day i.e. 10 AM to 4 PM. The individuals with this disorder report being more alert and productive at night. Many believe that genetic and hormonal factors contribute to this disorder but, in most of the cases, the behavioral factors are responsible for its perpetuation.
Advanced sleep phase disorder – In this disorder, sleep onset and wake-up time are advanced in relation to normally accepted sleep schedules i.e. 10 PM to 6 AM. It is commonly found in older adults. The individuals are unable to stay awake up to the normal bedtime and fall asleep in the afternoon or evening. They have difficulty in maintaining the sleep throughout the night and get up earlier than intended.
Shift work disorder – It occurs in people who change their work hours frequently or who work at night. Their work schedules are not in sync with their sleep and wake cycle. Some individuals have more difficulty in adjusting to these changes than others, especially individuals with advancing age.
Jet lag disorder - The circadian rhythm disruptions occur as jet lag during long air travels across more than two time zones, which make the travelers feel weak and have difficulty thinking and performing well.
Ill effects of circadian rhythm disruption –
Mood disorders - The disruption of circadian rhythm by lighting conditions and lifestyle predisposes the individuals to a number of mood disorders such as impulsivity, mania and depression. Commonly, the depressed individuals show an improvement of their mood in the evening. In depressive patients, the nocturnal melatonin release is diminished. That is why, approximately, 90 % of depressive patients complain about low quality of their sleep. There appears to be a link between sleep disorders and depression. That is why the therapy with anti-depressant drugs improves the quality of sleep in depressive persons. The depressive individuals also display increased levels of plasma cortisol, a hormone associated with stressful conditions.
In winters, when days are shorter, depression is developed as a consequence of diminished exposure to sunlight. Winter depression is characterized by hyper-somnia, increased appetite and overweight.
The disturbance of circadian rhythm exacerbates a depressive state due to altered patterns of secretions of serotonin, nor-adrenaline and dopamine, all of which regulate mood.
Metabolic disorders – The adverse effects of disturbance in circadian rhythm include development of type-2 diabetes and obesity after age, BMI and other various variables are taken into account. It is interesting to note that obesity is recognized to involve a low grade inflammatory state, which can be caused by the disturbance in circadian rhythm.
Cardiovascular disorders - It has been recognized that chronic circadian disruption may increase susceptibility to adverse cardiovascular events including myocardial infraction, sudden cardiac death, pulmonary embolism, limb ischemia and aortic aneurysm rupture. The shift work is associated with 1.6 and 3.0 fold increased risk of cardiovascular disease for 45 to 55 years old men and women respectively.
Hepatic function disorder - The clock disruption may impact multiple components of hepatic lipid homeostasis, affecting both bile acid and apo-lipoprotein biosynthesis.
Immune system disorder – Another adverse aspect of disturbance of circadian cycle is a deleterious effect on the immune system. Sleep disturbance deregulates monocyte production of several pro-inflammatory cytokines including interleukin-6 and tumor necrosis factor alpha, thereby increasing inflammation in the body.
Reproductive organs disorder – Melatonin blocks the secretion of gonadotrophins – luteinizing hormone and follicle stimulating hormone – from the anterior pituitary gland, which are responsible for the proper development and functioning of ovaries and testes. So, any disruption of circadian rhythm may affect the development and function of reproductive organs.
Cancer – An association between reduced melatonin secretion due to circadian cycle disturbance and a variety of cancers has been found. Male night shift workers have been found to have an increased risk of prostate cancer. Melatonin suppression due to prolonged exposure to light at night among female nurses has been associated with an increased risk of breast and colorectal cancer. Colorectal cancer may in part be the consequence of altered intestinal microbiota, caused by the disruption of circadian rhythm. Chemotherapy has been shown to be better tolerated in patients treated with melatonin.
Rheumatoid arthritis – Patients with rheumatoid arthritis have disturbances in the hypothalamic-pituitary-adrenal axis, which are reflected in altered circadian rhythm of circulating serum cortisol, melatonin and interleukin-6 (IL-6) levels.
Inflammatory bowel disease – A recent study conducted by researchers at Rush University Medical Centre indicates that a disruption of circadian rhythm when combined with high fat diet and high sugar diet may contribute to inflammatory bowel disease.
The disturbances of circadian rhythm is increasingly becoming common, especially in adolescents and younger adults due to their lifestyle and increasing work pressure. Many adults have become workaholic due to intense workplace competitiveness. Children are also affected by the ill effects of not adhering to the normal sleep pattern; to a large extent, their parents are responsible for allowing their children to incur damage to their health.
It is commonplace these days to travel long distances by air across more than two time zones, which also disturbs the circadian cycle in travelers. Majority of the blind persons suffer from the ill effects of the disruption of circadian cycle. Moreover, it has been well established that the shift workers increase their risk of developing obesity, cardiovascular diseases, and cancers; their immune system is also weakened due to working in shift.
So, it appears how important it is to maintain a normal circadian rhythm as well as normally accepted daily sleep pattern i.e. 10 PM to 6 AM in order to derive the health benefits of regular, sound sleep.