Chronobiology: Rhythms and Zeitgebers

Basic Chronobiology Concepts

• Chronobiology is the biological field that studies the effects of biological rhythms on essential life processes.
• Biological rhythms include circadian, ultradian, and infradian rhythms.
• Circadian rhythms have a duration of approximately 24 hours, examples of which include Core body temperature, Metabolic activity, Serum cortisol, and the Sleep–wake cycle
• Ultradian rhythms have a duration of less than 24 hours, such as Growth hormone and 90 minute REM sleep cycle
• Infradian rhythms have a duration of more than 24 hours, examples being Menstrual and reproductive cycles

Zeitgeber

• Zeitgebers are external or environmental cues that synchronize an organism's biological rhythms.
• Examples of zeitgebers include the day/night cycle, physical activity, melatonin levels, cortisol levels, and body temperature.

Circadian Rhythm and Melatonin.

• Cells in the suprachiasmatic nucleus of the hypothalamus induce the pineal gland to produce melatonin when light decreases.
• Melatonin secretion is inhibited by the pineal gland when light exposure increases.

Orexin/Hypocretin

• Orexin or Hypocretin is a hypothalamic neuropeptide that maintains sleep/wakefulness states.
• Cell bodies are located in the dorsolateral hypothalamus and project to the locus coeruleus, dorsal raphe nuclei, amygdala, and SCN.
• Central administration of orexin-A strongly promotes wakefulness.
• Orexin-A increases body temperature and locomotion.
• Orexin-A elicits an increase in energy expenditure.

Glossary of Terms

• A night owl has a late sleep onset and wakes up late in the morning.
• A morning person has an early sleep onset and wakes up early.
• Sleep debt refers to the consequences of not getting an optimal amount of sleep.
• Jet lag is a condition that affects people who travel frequently and across multiple time zones.
• Dream-enacting behaviors involves motor responses to the content of action-filled or violent dreams of being attacked or trying to escape a threatening situation.

Sleep Architecture

• Sleep architecture includes stages N1, N2, N3, and REM.
• A normal sleep hypnogram shows the sleep stages throughout the night, cycling approximately 6 times.
• A sleep cycle is generally 70-120 minutes in duration.

Sleep stages Brain Waves

• Awake relaxed state includes Alpha waves present
• 3% of sleep time is spent in stage 1 sleep
• 50% of sleep time is spent in stage 2 sleep, marked by the presence of Spindles(burst of activity)
• 10% of the cycle is spent in the Stage 3 sleep with K-complexes present
• 15% is normally spent in stage 4 sleep with Delta waves present
• 22% of the cycle is spent in REM sleep with a Sawtooth pattern present

Non-REM Sleep

• Non-REM sleep is characterized by decreased adrenergic and cholinergic activity,
• It is Controlled by the Ventrolateral preoptic area, an area of the hypothalamus

REM Sleep

• Rapid eye movement (REM) sleep is when the brain is very active, with discharges from the Pontine Reticular Formation.
• Perilocus Ceruleus inhibits motor activity during REM sleep
• Inhibited sensory input is present in REM sleep

Age-Appropriate Sleep Durations

• 6-month-olds: 11 hours nighttime, 3.5 hours daytime.
• 1-year-olds: 12 hours nighttime, 2 hours daytime.
• 2-year-olds: 11.5 hours nighttime, 2 hours daytime.
• 3-year-olds: 11 hours nighttime, 2 hours daytime.
• 4-year-olds: 11 hours nighttime, 1 hour daytime.
• 6-year-olds: 11 hours nighttime, 0 hours daytime.
• 8-year-olds: 10.5 hours nighttime, 0 hours daytime.
• 10-year-olds: 10 hours nighttime, 0 hours daytime.
• 13-year-olds: 9 hours nighttime, 0 hours daytime.
• +16-year-olds: 8 hours nighttime, 0 hours daytime.

Epidemiology of sleep disorders

• 50% of outpatient primary care clinic patients report sleep problems.
• Higher rates of sleep problems are seen in patients with psychiatric conditions.
• Insomnia is more frequent in psychiatric patients, the elderly, women, those with limited education or lower income and in those with multiple medical problems.
• Sleep apnea is more common in overweight patients.
• Sleep-wake disorders prevalence:
  • Insomnia affects 10-15% with a female to male ratio of 1.4:1.
  • Hypersomnolence disorder affects 1% with a 1:1 female to male ratio.
  • Narcolepsy affects 0.02-0.04% with a 1:1 female to male ratio.
  • Breathing-related sleep disorders affect 20% with a female to male ratio of 1:2 to 1:4.
  • Circadian rhythm sleep-wake disorders affect 11%.
  • Parasomnias affect 1-5%.
  • Restless legs syndrome affects 1-2% with a female to male ratio of 2:1.
  • Substance or medication-induced sleep disorder affects 0.38-0.5%.

Sleep assessment Inquiries

• Usual sleep pattern.
• Characteristics of sleep disturbance.
• Sleep history including sleep disturbances in the past
• The clinical course of the sleep disturbance
• 24-hour sleep-wake cycle.
• Sleep disturbance history, including childhood and under stress.
• Medication history.
• Illicit drug use.
• Alcohol, tobacco, and stimulant use.
• Use of hypnotics.
• Use of over-the-counter substances.
• Medical disorders.
• Family history.
• History of sleep disorders.
• Description by collateral if available.

Sleep Evaluation Techniques

• Polysomnography involves: Electroencephalography, Electrooculography, Electromyography
• Polysomnography findings include: Sleep continuity and architecture, REM physiology, Sleep-related breathing, Oxygen desaturation, Cardiac arrhythmias, and Periodic movements.
• The Multiple Sleep Latency Test measures how quickly a patient falls asleep in a quiet environment during the day.
• The Multiple Sleep Latency Test consists of five scheduled naps for 20 minutes every 2 hours during wakefulness.
• Sleep onset of fewer than 5 minutes on the Multiple Sleep Latency Test is considered pathologic.

Sleep Hygiene

• Maintain a regular sleep routine to promote consistent sleep patterns.
• Avoid naps if possible, as they can disrupt nighttime sleep.
• Don't stay in bed awake for more than 5-10 minutes.
• Don't watch TV or read in bed, to avoid associating the bed with wakeful activities.
• Drink caffeinated drinks with caution, as they can interfere with sleep.
• Avoid substances that interfere with sleep, such as alcohol and nicotine.
• Exercise regularly, but avoid strenuous exercise close to bedtime
• Ensure the bedroom is quiet and comfortable to promote restful sleep.
• Have a comfortable pre-bedtime routine to wind down before sleep.
• Hide the clock if you tend to clock-watch at night, reducing anxiety about sleep.