There are two types of sleep: non-rapid eye-movement (NREM) sleep and rapid eye-movement (REM) sleep. Over the course of a sleep period, NREM and REM sleep alternate cyclically.2 This basic structural organization is referred to as sleep architecture.
Two major processes – homeostatic drive and circadian rhythm, regulate the sleep-wake system. Homeostatic drive determines how much sleep is needed, and the circadian rhythm optimizes the ability to achieve that sleep at night.1-2
Neurobiology of Sleep
Beyond these concepts, the biological basis of sleepiness is not entirely understood, according to David Neubauer, MD, associate director of the Johns Hopkins Sleep Disorders Center.
Discovery of the retinal ganglion cells a decade ago advanced the understanding of how information is sent back through the retinal hypothalamic tract to the suprachiasmatic nucleus (SCN), which is the timekeeper of the circadian rhythm and results in entrainment to the light-dark cycle.
“The SCN links up with a lot of other nuclei of the hypothalamus and also controls the pineal gland, where melatonin is secreted,” Neubauer said, “This creates a feedback loop with the melatonin receptors in the SCN, and contributes to the robustness of the circadian cycle that is so obvious when we travel and experience jet lag.”
Another key piece of the sleep-wake cycle regulation puzzle was the identification of orexin, (also called hypocretin) a neurotransmitter associated with wakefulness, he added.
A major role of the orexin system is to integrate metabolic, circadian and sleep debt influences to determine whether an animal should be asleep, or awake and active, findings from recent studies suggest.
By contrast gamma-aminobutyric acid (GABA) plays a role in promoting sleep. In particular areas of the hypothalamus, the ventrolateral preoptic nucleus is activated during sleep. This appears to suppress stimulation that would occur from various other nuclei that promote wakefulness. Taken together, orexin and GABA form a complex system that balances sleep and wake.
Sleep Architecture & Psychiatric Conditions
Disruptions of either the homeostatic or circadian systems can lead to a variety of sleep disorders that can affect obesity, cardiovascular disease, diabetes, and mental health.
Insomnia is among the most common sleep disorders health care providers. Nighttime insomnia accompanied by daytime impairment affects 6% to 10% of healthy adults. Its prevalence is considerably higher in people with mental health disorders, especially mood, anxiety, stress-related, neurocognitive, and psychotic disorders.3
Vishal Madaan, MD, director of the Child and Family Psychiatry Clinic at the University of Virginia in Charlottesville, explained that sleep disorders, including insomnia, have become more common in adolescents and young adults with increased use of electronics, video games, cell phones and social media.
In one study, adolescents rated themselves as significantly more tense/anxious, angry/hostile, confused, and fatigued when their sleep was restricted by 2.5 hours compared to when they received up to 10 hours of sleep per night.4
Treating Sleep Disorders
Before considering pharmacologic interventions, it is important to assess the basics, particularly in the adolescent population.
“We first look at sleep hygiene,” Madaan said. “It is important to make sure the TV and video games are out of the child’s room. Establish a routine, taking a warm shower, not getting involved in an aggressive video game two hours before bed, and limiting screen time.”
If those measures do not help, prescribing medications will depend on clinical presentation.
If a patient comes in with ADHD-related symptoms and is struggling with sleep, clonidine may help both disruptive behavior symptoms and sleep, Madaan advised. Benzodiazepine and similar medications should be avoided in these patients because of addiction risks and associated hyperarousal response.
Pharmacological treatments for circadian misalignment generally focus on the melatonin system.
Ramelteon (Rozerem), a melatonin receptor agonist, is indicated for sleep onset insomnia. Agomelatine, which is not FDA-approved, has a dual pharmacology that works on both the melatonin and serotonin systems, according to Neubauer.
“In terms of emerging medications, the orexin receptor antagonists are interesting,” Neubauer said.
These drugs function by blocking orexins, a chemical known to stimulate wakefulness and arousal. “None are approved yet, but many are under investigation. Suvorexant is furthest along,” he explained
Homeostatic drive and circadian rhythms regulate sleep. Disruptions in these processes can lead to multiple health issues and are associated with mental health disorders.
Medications targeting the neurobiology of either the sleep or wake cycle need to be used with caution, especially in adolescents and young adults, and are considered second line therapies after promoting good sleep hygiene.
Michael O’Leary is a freelance medical writer based in the greater Seattle Area. This article has been medically reviewed by Pat F. Bass III, MD, MS, MPH.
- Baron KG, Reid KJ. “Circadian misalignment and health.” Int Rev Psychiatry. 2014; 26(2):139-154.
- National Research Council. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Washington, DC: The National Academies Press, 2006.
- Neubauer DN. “New and emerging pharmacotherapeutic approaches for insomnia.” Int Rev Psychiatry.2014; 26(2) 214-224.
- Baum KT et al. “Sleep restriction worsens mood and emotion regulation in adolescents.” J Child Psychol Psychiatry. 2014; 55:2:180-190.