What Causes Insomnia?

Need byline and synopsis

Insomnia has many causes; most of them include some type of disruption of neural regulation of the circadian rhythms and the sleep-wake cycle, which can be due to numerous factors. Before we discuss those factors, let’s discuss the circadian rhythm, sleep homeostasis, the hypothalamic-pituitary-adrenal (HPA) axis, and the pineal gland.


Circadian Rhythms, Sleep Homeostasis, the Pineal Gland and the HPA Axis

Circadian Rhythms

Circadian rhythms are cyclical, 24-hour biological processes, which include fluctuations in hormone levels, body temperature, and sleep. In humans, circadian rhythms are a function of several brain regions, but mainly neurons located in the hypothalamus, specifically in an area of the hypothalamus called the suprachiasmatic nucleus (SCN).

Sleep Homeostasis

Homeostasis is the process by which the body attempts to maintain a steady state. The longer you are awake, the more your body ‘craves’ sleep to restore homeostasis. When it comes to sleep homeostasis, the body relies on neurotransmitters and hormones, such as adenosine, corticotropin-releasing hormone (CRH), melatonin, corticotropin, and cortisol. In addition to the hypothalamus, other areas involved in sleep homeostasis include the pineal gland, the thalamus, the pituitary gland, and the reticular formation within the brain stem.

The Pineal Gland

Both circadian rhythms and sleep homeostasis are influenced by the neurochemical melatonin, which is secreted by a gland in the brain called the pineal gland. The pineal gland produces melatonin in response to darkness and inhibits the production of melatonin in response to light. The pineal gland also effects the production of other hormones, such as sex hormones, by influencing the pituitary gland.

The Hypothalamic-Pituitary Axis (HPA)

The hypothalamus and pituitary gland are part of a system called the hypothalamic-pituitary-adrenal (HPA) axis. This axis is responsible for a number of functions, including regulation of the sleep-wake cycle through neural signaling and hormone production.

Primary & Secondary Insomnia

Chronic insomnia can be categorized as primary insomnia, meaning that the patient experiences insomnia as its own distinct disorder, and secondary insomnia, which is due to another cause, such as a medical condition or side effects of medication.  Insomnia has numerous causes, which include:

  1. A neurochemical disorder in the pineal gland 1
  2. A disorder of the circadian rhythm, which is a function of the suprachiasmatic nucleus (SCN) located at top of the mesencephalon 2
  3. A disorder in the HPA axis 3 – 13
  4. A result of disorder in the renin-angiotensin-aldosterone (RAA) axis 14
  5. A result of hormonal disorder, related to network connections between the brain, pineal gland, autonomic centers and the gonads (what happens is that anytime you have decrease in reproductive hormones, then you disrupt the cortisol regulation, and when you disrupt cortisol regulation then the brain cannot regulate its internal neurotransmitters; you lose sync and you can’t sleep. 3 – 13
  6. Dysglycemia (hypoglycemia and hyperglycemia) 15 16
  7. Generalized swelling due to liver or kidney disorder-activation of RAAA axis
  8. Leaky gut 17
  9. Shift in line of pressure (if you have any deviation of body posturing, whether anterior or posterior (pushed forward or pushed backwards). This increases adrenaline, because the brain is always alert)
  10. Secondary insomnia, or comorbid insomnia, is insomnia in addition to some other medical condition or side effect of medication.

Many times, patients with other conditions experience insomnia, such as those listed below. Often, the insomnia is due to one or more of the reasons listed above.

  • Psychiatric disorders 18, including depression and anxiety 19
  • Fibromyalgia Syndrome (FMS) 20
  • Irritable Bowel Syndrome (IBS) 21
  • Chronic Fatigue Syndrome (CFS) 22
  • Attention Deficit Disorder/Attention Deficit/Hyperactivity Disorder (ADD/ADHD) 23
  • Autistic Spectrum Disorders (ASDs) 24
  • Restless Leg Syndrome (RLS) 25
  • Neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease 26
  • Multiple Sclerosis (MS) 27
  • Amyotrophic Lateral Sclerosis (ALS) 28
  • Chronic pain syndromes 29
  • Vascular diseases and cardiovascular diseases 30
  • Respiratory conditions 31 32
  • Plus many, many others

Every condition listed above has some effect on the functioning of the central nervous system (CNS), autonomic nervous system (ANS), peripheral nervous system (PNS), and enteric nervous system (ENS). When the nervous system starts to dysfunction, we end up with myriad symptoms including problems with sleep.


  1. Haimov I, et al. Sleep disorders and melatonin rhythms in elderly people. Bmj 309.6948 (1994): 167.
  2. Zisapel N. Circadian rhythm sleep disorders. CNS drugs 15.4 (2001): 311-328.
  3. Buckley TM, Schatzberg AF. On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. The Journal of Clinical Endocrinology & Metabolism 90.5 (2005): 3106-3114.
  4. Vgontzas AN, et al. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. The Journal of Clinical Endocrinology & Metabolism 86.8 (2001): 3787-3794.
  5. Vgontzas AN, et al. Chronic insomnia and activity of the stress system: a preliminary study. Journal of psychosomatic research 45.1 (1998): 21-31.
  6. Rodenbeck A, et al. Interactions between evening and nocturnal cortisol secretion and sleep parameters in patients with severe chronic primary insomnia. Neuroscience letters 324.2 (2002): 159-163.
  7. Rodenbeck A, Hajak G. Neuroendocrine dysregulation in primary insomnia. Revue neurologique 157.11 Pt 2 (2001): S57-61.
  8. Roth T, Roehrs T, Pies R. Insomnia: pathophysiology and implications for treatment. Sleep medicine reviews 11.1 (2007): 71-79.
  9. Roth T. Insomnia: definition, prevalence, etiology, and consequences. Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 3.5 Suppl (2007): S7.
  10. Buckley TM, Mullen BC, Schatzberg AF. The acute effects of a mineralocorticoid receptor (MR) agonist on nocturnal hypothalamic–adrenal–pituitary (HPA) axis activity in healthy controls. Psychoneuroendocrinology 32.8 (2007): 859-864.
  11. Basta M, et al. Chronic insomnia and the stress system. Sleep medicine clinics 2.2 (2007): 279-291.
  12. Antonijevic I. HPA axis and sleep: Identifying subtypes of major depression: Review. Stress: The International Journal on the Biology of Stress 11.1 (2008): 15-27.
  13. Vgontzas AN. The diagnosis and treatment of chronic insomnia in adults. Sleep 28.9 (2005): 1047-1050.
  14. Pannain S, Van Cauter E. Modulation of endocrine function by sleep-wake homeostasis and circadian rhythmicity. Sleep Medicine Clinics 2.2 (2007): 147-159.
  15. Salzer HM. Relative hypoglycemia as a cause of neuropsychiatric illness. Journal of the National Medical Association 58.1 (1966): 12.
  16. Nakajima H, et al. Insomnia symptoms associated with hyperglycemia. Sleep and Biological Rhythms 8.3 (2010): 203-211.
  17. Mellowship, Dawn. Leaky Gut Syndrome.
  18. Breslau N, et al. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biological psychiatry 39.6 (1996): 411-418.
  19. Taylor DJ, et al. Epidemiology of insomnia, depression, and anxiety. SLEEP-NEW YORK THEN WESTCHESTER- 28.11 (2005): 1457.
  20. Jennum P, et al. Sleep and other symptoms in primary fibromyalgia and in healthy controls. The Journal of rheumatology 20.10 (1993): 1756-1759.
  21. Jarrett M, et al. Sleep disturbance influences gastrointestinal symptoms in women with irritable bowel syndrome. Digestive diseases and sciences 45.5 (2000): 952-959.
  22. Morriss RK, Wearden AJ, Battersby L. The relation of sleep difficulties to fatigue, mood and disability in chronic fatigue syndrome. Journal of psychosomatic research 42.6 (1997): 597-605.
  23. Cantwell DP. Attention deficit disorder: a review of the past 10 years. Journal of the American Academy of Child & Adolescent Psychiatry 35.8 (1996): 978-987.
  24. Miano S, Ferri R. Epidemiology and management of insomnia in children with autistic spectrum disorders. Pediatric Drugs 12.2 (2010): 75-84.
  25. Ekbom K-A. Restless legs syndrome. Neurology 10.9 (1960): 868-868.
  26. Dauvilliers Y. Insomnia in patients with neurodegenerative conditions. Sleep medicine 8 (2007): S27-S34.
  27. Stanton BR, Barnes F, Silber E. Sleep and fatigue in multiple sclerosis. Multiple sclerosis 12.4 (2006): 481-486.
  28. Takekawa H, et al. Amyotrophic lateral sclerosis associated with insomnia and the aggravation of sleep‐disordered breathing. Psychiatry and clinical neurosciences 55.3 (2001): 263-264.
  29. Wilson KG, et al. Major depression and insomnia in chronic pain. The Clinical journal of pain 18.2 (2002): 77-83.
  30. Schwartz S, et al. Insomnia and heart disease: a review of epidemiologic studies. Journal of psychosomatic research 47.4 (1999): 313-333.
  31. George CFP, Bayliff CD. Management of insomnia in patients with chronic obstructive pulmonary disease. Drugs 63.4 (2003): 379-387.
  32. Klink ME, Dodge R, Quan SF. The relation of sleep complaints to respiratory symptoms in a general population. Chest Journal 105.1 (1994): 151-154.

Write a comment

Comments: 2