Sleep Disorders (Insomnia): Causes

Pathogenesis (development of disease)

The pathogenesis of the various forms of insomnia is very diverse and cannot be explained by a common pathomechanism. Chronic stress significantly impairs sleep quality. Cortisol levels are markedly elevated in insomnia. Stress and the resulting elevated cortisol levels activate the tryptophan-degrading enzyme tryptophan pyrrolase. Tryptophan is necessary for the production of the two important neurotransmitters serotonin and melatonin. Through the formation of serotonin, tryptophan has an indirect influence on sleep and, through its antidepressant effect, on general mood. Melatonin, a hormone of the pineal gland, has a sleep-promoting effect and controls the day-night rhythm. Increased cortisol reduces deep sleep phases and REM sleep. Furthermore, increased cortisol triggers insomnia. Furthermore, melatonin production decreases and the prevalence (frequency of illness) of sleep disorders increases in both sexes from about 50 years of age. For the topic “sleep, sleep stages, sleep phases, sleep rhythms, etc.” see under the topic of the same name. For the importance of melatonin or tryptophan and sleep, see “Melatonin” and “Tryptophan” below.

Etiology (causes)

Biographic causes

  • Genetic burden
    • Often familial: heritability (inheritability) of insomnia or sleep maintenance is estimated at 59% in women and 38% in men; a genome-wide association study (GWAS) with 113,006 participants identified seven risk genes for insomnia; among them is the gene “MEIS1,” which has already been identified as a risk gene for restless legs syndrome (see below Restless Legs Syndrome); it is now known that 956 genes in 202 different locations of the genome influence sleep characteristics.
    • Sleepwalking (moonstruck, somnambulism): three and seven times higher in the case of one and two affected parents, respectively.
    • Night terrors (Pavor nocturnus); familial clustered, but to a lesser extent than sleepwalking.
      • Genetic disorders
        • Huntington’s chorea (synonyms: Huntington’s chorea or Huntington’s disease; older name: St. Vitus’ dance) – genetic disorder with autosomal dominant inheritance characterized by involuntary, uncoordinated movements accompanied by flaccid muscle tone.
        • Fatal familial insomnia (lethal familial insomnia) – genetic disorder with autosomal-dominant inheritance; spongiform encephalopathy (TSE); characterized by refractory insomnia with dreams and hallucinations; motor disturbances and possibly dementia occurring late in its course
        • Hereditary ataxia – autosomal recessive or autosomal dominant inherited (ADCA = autosomal dominant cerebellar ataxias) disorders of movement (ataxias); symptoms include increasing gait unsteadiness, fine motor dysfunction, slurred speech, and eye movement disorders
  • Age – increasing age (the phases of deep sleep and the depth of sleep decrease, the tendency to awaken at night increases).
  • Hormonal factors
    • 17-Beta estradiol fluctuation, deficiency, and decline in women.
    • During menstruation (menstrual period).
    • In and after perimenopause – transitional phase between premenopause and postmenopause; different length of years before menopause (menopause in women) – about five years – and after menopause (1-2 years).
    • Andropause (menopause of men)
  • Occupations – occupations with shift work (night work, rotating shift and evening work); occupations (pilots, cabin crew) that lead to jet lag (travel across multiple time zones).

Behavioral causes

  • Nutrition
    • Physiological causes – eating or drinking at night.
  • Consumption of stimulants
    • Alcohol
    • Coffee, tea (caffeine)
    • Tobacco (smoking)
  • Drug use
  • Physical activity
    • Immobility and bedriddenness (common causes of insomnia in the elderly).
    • Sitting activity or sitting too long.
    • Competitive sports
    • Professional sports
    • Intense exercise <1 hour before bedtime → longer time to fall asleep and less total sleep
  • Psycho-social situation
    • Psychological causes such as anger, unresolved problems, marital crises, stressful situations, overwork, pressure to perform.
    • Computer and internet use: a strong association was shown with:
      • Girls: excessive music listening (≥ 3 h/daily).
      • Boys: Use of computer or Internet (≥ 3 h/ daily).
      • Total time spent in front of an electronic device screen (≥ 8 h/ daily).
      • Chronic stress (including at work; shift work).
  • Lack of the usual sleep ritual or poor sleep hygiene.
  • Overweight (BMI ≥ 25; obesity) – is also associated with sleep apnea.

Disease-related causes

Respiratory system (J00-J99)

  • Allergic rhinitis (allergic rhinitis; hay fever).
  • Bronchial asthma
  • Chronic obstructive pulmonary disease (COPD)
  • Chronic rhinosinusitis (CRS; simultaneous inflammation of the nasal mucosa (“rhinitis”) and the mucosa of the paranasal sinuses (“sinusitis“)).

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Andropause (male menopause)
  • Hyperthyroidism (hyperthyroidism)
  • Climacteric (menopause in women; eg, hot flashes).

Factors influencing health status and leading to health care utilization (Z00-Z99).

  • Burnout syndrome

Cardiovascular system (I00-I99)

  • Apoplexy (stroke)
  • Heart failure (cardiac insufficiency)

Mouth, esophagus (esophagus), stomach, and intestines (K00-K67; K90-K93).

  • Gastroesophageal reflux disease (synonyms: GERD, gastroesophageal reflux disease; gastroesophageal reflux disease (GERD); gastroesophageal reflux disease (reflux disease); gastroesophageal reflux; reflux esophagitis; reflux disease; reflux esophagitis; peptic esophagitis) – inflammatory disease of the esophagus (esophagitis) caused by the pathological reflux of acidic gastric juice and other gastric contents [75% of cases no typical symptoms! Irritation of the throat, hoarseness, cough, “asthma”]

Musculoskeletal system and connective tissue (M00-M99).

Neoplasms – tumor diseases (C00-D48).

  • Brain tumors

Psyche – nervous system (F00-F99; G00-G99)

  • Alcohol dependence
  • Anxiety disorders
  • Bipolar disorder (manic-depressive disorder)
  • Chronic pain
  • Dementia
  • Depression
  • Drug addiction
  • Dystonia – umbrella term for neurological disorders in which the mobility of certain regions of the body is disturbed, without this disturbance can be influenced at will.
  • Epilepsy – neurological disease that leads to seizures.
  • Idiopathic insomnia – sleep disorder with no apparent cause.
  • Mania (pathological high spirits)
  • Meningitis (meningitis)
  • Meningoencephalitis – combined inflammation of the brain (encephalitis) and meninges (meningitis).
  • Alzheimer’s disease
  • Parkinson’s disease (shaking palsy)
  • Multiple sclerosis (MS) – neurological disease that leads to multiple damage to the central nervous system due to a chronic inflammatory response.
  • Narcolepsy – disease that usually begins in childhood and leads to short sleep seizures.
  • Obstructive sleep apnea syndrome (OSAS) – characterized by obstruction or complete closure of the upper airway during sleep; most common form of sleep apnea.
  • Panic disorder
  • Parasomnia (nightmares, Pavor nocturnus and sleepwalking/somnabulism).
  • Parkinson’s syndrome – neurological disease (extrapyramidal syndrome due to degeneration of dopaminergic neurons in the substantia nigra).
  • Polyneuropathies – diseases of the peripheral nervous system affecting multiple nerves.
  • Post-traumatic stress disorder (PTSD).
  • Prion diseases – the most common clinical manifestation is Creutzfeld-Jakob disease.
  • Psychosis
  • Psychophysiological insomnia – insomnia due to emotional tension.
  • Restless legs syndrome (RLS; restless legs syndrome)/nocturnal periodic leg movements syndrome.
  • Schizophrenia – psychiatric disorder that causes changes in thoughts, perception, and behavior.
  • Central sleep apnea syndrome (SAS) – characterized by repeated respiratory arrests due to lack of respiratory muscle activation (episodic inhibition of respiratory drive).

Symptoms and abnormal clinical and laboratory findings not elsewhere classified (R00-R99)

  • Cephalgia (headache)
  • Nocturia (urination at night)
  • Pruritus (itching)
  • Pain, unspecified (e.g., in chronic diseases).

Genitourinary system (kidneys, urinary tract – reproductive organs) (N00-N99).

  • Benign prostatic hyperplasia (BPH; benign prostatic enlargement) → nocturia (increased urination at night).
  • Lower urinary tract symptoms (LUTS); in or through sleep disturbances are also a risk factor for greater LUTS severity.

Injuries, poisonings, and other sequelae of external causes (S00-T98).

Medication

* Administered at low doses, levodopa appears to be sleep-inducing, but suppressive at higher doses. * * Limited fitness to drive due to sudden sleep attacks.

Operations

Environmental exposure – Intoxications (poisonings).

  • Physical causes – altitude-induced sleep disturbance, noise (esp. night noise/noise from aircraft), bright lights, high temperatures, etc.
  • Residential and environmental toxins – particle board, paints, wood preservatives, wall paint, floor coverings, etc.

Other causes

  • Nightmares
  • Lack of social contact, loneliness, worry (common causes of insomnia in old age).
  • Gravidity (pregnancy)
  • Mechanical heart valve (→ valve noise); recommendation: sleep on the right side (reduces noise).
  • Disturbance of the biorhythm
    • Light from e-book readers, smartphones, laptops or tablet PCs (higher blue content than that of a bedside lamp) switches the internal clock into sleep mode with a delay.
    • Time zone change (jet lag), etc.
  • Snoring

Sleep disorders and their effects on a wide range of important physical and mental functions are a major factor of both causative and triggering importance in a number of aging mechanisms. Sleep disturbances may themselves also be a symptom of aging processes.