3. Pineal Gland and Circadian Rhythms

Pineal Gland and Circadian Rhythms

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

The role of this gland has long been contemplated by philosophers and sages. Ancient Greeks believed the pineal gland to be our connection to the Realms of Thought. Descartes called it the Seat of the Soul.[1] The gland controls the various biorhythms of the body in response to light and dark. It works in harmony with the hypothalamus which directs the body's thirst, hunger, sexual desire and the biological clock that determines the ageing process.

There are 6 fundamental rhythms that harmonise with day and night:

  • Sleeping and waking
  • Cortisol secretion (highest at dawn)
  • Intellectual performance (best at about noon)
  • Body temperature (highest in the afternoon)
  • Prolactin secretion (highest at night)
  • Melatonin (N-acetyl-5-methoxytryptamine) - half-life ~45 minutes - only secreted at night, can reset sleep onset through its synchronising effect on the biological clock[2]

Diurnal means recurring every day (Latin diurnalis, daily) and is chiefly used to describe the activities of heavenly bodies as well as biological rhythms that have a 24-hour cycle.

Circadian designates physiological activity which recurs approximately every 24 hours, or the rhythm of such activity (Latin circa, about, plus dies, day).

Circadian synchrony consists of keeping all these clocks in time with each other and with the diurnal rhythms of the solar system. The biological clock is in the suprachiasmatic nucleus of the hypothalamus and depends on melatonin, the hormone of darkness, to inform it of time and its passing.[2] Melatonin is secreted by the pineal gland but if darkness fails, as on an intercontinental flight, or during a night on call, synchrony is broken until melatonin is restored, either artificially, or by night. Jet lag causes malaise, light headedness, insomnia and reduced cognition. Its effects are minimised by avoiding insomnia during and immediately after flight across time zones.[3] Reduced cognition to the person who is on call means impaired performance. Impaired performance after long journeys across time zones can be critical to elite athletes and advice about sleep regimes is required. There have been suggestions that melatonin may be useful to treat jet lag and it may even be valuable to treat night shift workers. The latter suffer an array of problems including disturbances of sleeping or gastrointestinal disorders, depression, cardiovascular diseases, obesity and disturbed sexual activity and sub-fertility.[4][5]

Administration of melatonin may cause irresistible sleep but it can be very irregular with abnormal cycles. These effects can be explained if melatonin chiefly acts on sleep timing and, if it is given at the wrong time, it may disrupt normal patterns. It is only soporific if given during the day or early evening, when endogenous levels are low. Melatonin is released during darkness even by animals that are nocturnal.The role of melatonin in sleep is far from clear. Meta-analyses have failed to confirm the usefulness of melatonin for the treatment of insomnia in age groups younger than 55 but do confirm a role in patients of any age with intellectual disability.[6].

To avoid jet lag for stays of 4 days or more, the Centre for Chronobiology at the University of Surrey recommends timed exposure to and avoidance of light.[7] Other options are being investigated including timed exercise, timed and selective diets, social stimuli and the use of melatonin agonists.[8]

Melatonin levels have been found to be closely associated with the sleep disturbance of depression. One study found that agomelatine, which combines the properties of a 5-HT antagonist and a melatonergic receptor agonist, has been found very effective for resetting the disturbed sleep/wake cycle and in improving the clinical status of major depressive disorder.[9]

Other roles identified for melatonin include involvement in the functioning of the immune system and cancer initiation. The newly discovered free radical scavenging and antioxidant activities of melatonin may also be important.[10]

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The pineal gland is large in children but shrinks at puberty. It appears to play a major role in sexual development, hibernation in animals, metabolism and seasonal breeding. The high melatonin level in children is believed to inhibit sexual development until puberty arrives and melatonin production is reduced.[11] This may account for some of the behavioural problems of adolescence.[12] Melatonin may also play a role in other aspects of human reproduction such as protection of the fetus from oxidative processes and beneficial effects on the outcome of in vitro fertilisation.[13] The pineal gland is involved in both normal and abnormal puberty.[14]

In the elderly with sleep disturbance, melatonin production is impaired compared with age-matched controls. The activity of the pineal gland declines with advancing age and more so with Alzheimer's disease.[15] One study of the effect of prolonged-release melatonin found that patients over 55 found a significant improvement in sleep and in psychomotor performance the following day compared to placebo.[16] Sleep disturbance is an important feature of Alzheimer's disease but the results of trials with melatonin have been equivocal.[17] One study failed to find a beneficial effect, whereas another using melatonin-enriched night-time milk found that it increased the activity of elderly patients during the day.[18][19]

Melatonin is now licensed for use in the UK for the short-term management of insomnia in the over-55s under the brand name Circadia®.[20] Melatonin may also confer more widespread protective benefits against the ageing process but further research is required.[21]

Seasonal affective disorder (SAD) occurs in higher latitudes in the short days of winter and is characterised by depression, fatigue, hypersomnolence, hyperphagia, carbohydrate craving, weight gain and loss of libido. The condition reverses as days grow longer again. A number of treatments have been used including light exposure, L-tryptophan, Hypericum perforatum (St. John's wort) and melatonin. The condition affects between 1 and 3% of people in temperate climates and is commoner in women. Exposure to 2,000 to 10,000 lux for 30 to 120 minutes daily during the winter improves the condition.[22]

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Further reading & references

  1. Descartes and the Pineal Gland; Stanford Encyclopaedia of Philosophy 2005
  2. Garfinkel D, Laudon M, Nof D, et al; Improvement of sleep quality in elderly people by controlled-release melatonin; Lancet. 1995 Aug 26;346(8974):541
  3. Waterhouse J, Reilly T, Edwards B; The stress of travel. J Sports Sci. 2004 Oct;22(10):946
  4. Nicholson PJ, D'Auria DA; Nicholson PJ, D'Auria DA; Shift work, health, the working time regulations and health assessments. Occup Med (Lond). 1999 Apr;49(3):127-37.
  5. Rudiger HW; Health problems due to night shift work and jetlag. Internist (Berl). 2004 Sep;45(9):1021-5.
  6. Braam W, Smits MG, Didden R, et al; Exogenous melatonin for sleep problems in individuals with intellectual disability: a meta-analysis. Dev Med Child Neurol. 2009 May;51(5):340-9.
  7. Arendt J; Managing jet lag: Some of the problems and possible new solutions. Sleep Med Rev. 2009 Aug;13(4):249-56. Epub 2009 Jan 14.
  8. Brown GM, Pandi-Perumal SR, Trakht I, et al; Melatonin and its relevance to jet lag. Travel Med Infect Dis. 2009 Mar;7(2):69-81. Epub 2008 Oct 31.
  9. Srinivasan V, Pandi-Perumal SR, Trakht I, et al; Pathophysiology of depression: role of sleep and the melatonergic system. Psychiatry Res. 2009 Feb 28;165(3):201-14. Epub 2009 Feb 1.
  10. Reiter RJ; Melatonin: clinical relevance. Best Pract Res Clin Endocrinol Metab. 2003 Jun;17(2):273-85.
  11. Reiter RJ; Melatonin and human reproduction. Ann Med. 1998 Feb;30(1):103-8.
  12. Carskadon MA, Acebo C, Jenni OG; Regulation of adolescent sleep: implications for behavior. Ann N Y Acad Sci. 2004 Jun;1021:276-91.
  13. Reiter RJ, Tan DX, Manchester LC, et al; Melatonin and Reproduction Revisited. Biol Reprod. 2009 May 13.
  14. Macchi MM, Bruce JN; Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol. 2004 Sep-Dec;25(3-4):177-95.
  15. Skene DJ, Swaab DF; Melatonin rhythmicity: effect of age and Alzheimer's disease. Exp Gerontol. 2003 Jan-Feb;38(1-2):199-206.
  16. Luthringer R, Muzet M, Zisapel N, et al; The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. Int Clin Psychopharmacol. 2009 Sep;24(5):239-49.
  17. Cardinali DP, Brusco LI, Liberczuk C, et al; The use of melatonin in Alzheimer's disease. Neuro Endocrinol Lett. 2002 Apr;23 Suppl 1:20-3.
  18. Baskett JJ, Broad JB, Wood PC, et al; Does melatonin improve sleep in older people? A randomised crossover trial. Age Ageing. 2003 Mar;32(2):164-70.
  19. Valtonen M, Niskanen L, Kangas AP, et al; Effect of melatonin-rich night-time milk on sleep and activity in elderly institutionalized subjects. Nord J Psychiatry. 2005;59(3):217-21.
  20. British National Formulary
  21. Karasek M; Melatonin, human aging, and age-related diseases. Exp Gerontol. 2004 Nov-Dec;39(11-12):1723-9.
  22. Magnusson A, Boivin D; Seasonal affective disorder: an overview. Chronobiol Int. 2003 Mar;20(2):189-207.
Original Author: Dr Laurence Knott Current Version:
Last Checked: 15/10/2009 Document ID: 2613  Version: 21 © EMIS

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

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