- Sleep Disorders
- Health Benefits of Sleep
- Effects of Sleep loss
- Health Disorders Associated with Sleep Problems
- Other Effects of Sleep
Sleep is defined as a natural and reversible state of reduced responsiveness to external stimuli and relative inactivity, accompanied by a loss of consciousness (R).
Sleep occurs in regular intervals and there is a consistent need for sleep, so a loss or delay of sleep results in subsequently prolonged sleep (R).
There are two types of sleep non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM) sleep.
Rapid Eye Movement (REM) Sleep:
REM sleep is characterized by high-frequency low-voltage brain activity (as measured by an electroencephalogram) and bursts of rapid contractions of the eye muscles, causing the eyes to move rapidly.
A healthy young person’s normal night of sleep typically includes 4-5 distinct REM periods, accounting for 20% of the total time spent asleep (TSA) (R).
Non-Rapid Eye Movement (NREM) Sleep:
Most of the night is spent in non-REM sleep, which is further divided into 4 sub-stages (stages I-IV).
Stage I is the lightest stage of sleep
Stage II sleep is defined by the emergence of specific peaks in the electroencephalogram (EEG) (K-complexes and sleep spindles) and typically accounts for more than half of the night’s sleep.
Stage III and IV, the deepest states of sleep are characterized by slow brain waves, also called delta brain wave. Together stages III and IV are also referred to as “Slow wave sleep” (SWS).
For a healthy young person, the first progression through the four nonREM sleep stages typically takes 70-100 minutes.
Typical human sleep profile and sleep related signals
Over the course of a period of sleep both REM and NREM alternate cyclically.
Irregular cycling and/or the absence of sleep stages are associated with sleep disorders (R).
Primary sleep disorders include those not attributable to another medical or psychiatric condition and these include (R):
- Obstructive sleep apnea
- Central sleep apnea
- Parasomnias (abnormal activities during sleep, which could be walking, eating or sex)
Insomnia is a common sleep disorder. People who have insomnia have trouble falling asleep, staying asleep or both (R). As a result, they may get too little sleep or have poor-quality sleep.
Insomnia can be acute or chronic. Acute insomnia lasts for few days or weeks and is often brought on by psychological stresses such as work and family pressures etc.
Chronic insomnia which lasts for a month or longer is mostly secondary to other health issues (R).
- Parkinson’s disease
- Kidney disorders
- Heart failure
- Rhinitis (irritation and inflammation of mucous membrane inside the nose)
- Prostate hypertrophy (enlarged prostate gland).
Obstructive Sleep Apnea (OSA)
Ongoing obstructive sleep apnea is a sleep disorder that is marked by pauses in breathing for 10 seconds or more during sleep, causing unrestful sleep. Symptoms include loud or abnormal snoring, daytime sleepiness, irritability and depression (R).
Central Sleep Apnea
Central sleep apnea (CSA) is defined by the cessation of airflow without breathing effort (R).
This condition is different from obstructive sleep apnea in which ongoing the breathing effort is present during respiratory events (R). The patient simply stops breathing during sleep because the nervous system does not send proper signals to the breathing muscles during sleep.
Narcolepsy is a disorder that causes periods of extreme daytime sleepiness even after adequate sleep during the night (R).
Some narcoleptic patients fall asleep suddenly, even if they are in the middle of talking, eating or another activity.
Health Benefits of Sleep
1) Sleep Improves Memory
Sleep is essential for effective cognitive functioning (R).
Naps can reduce sleepiness and improve cognitive performance (R).
Memory is one of the essential cognitive functions involved in all other cognitive processes.
A short period of sleep prior to learning can enhance the capacity to encode new information (R).
In children, shortened sleep duration, especially before the age of 41 months, is associated with lower cognitive performance and developmental tests (R).
Humans totally deprived of sleep showed deficits in motor procedural, implicit memory and working memory (R).
2) Sleep Helps Remove Waste from the Brain
Sleep stimulates the clearance of metabolic waste from adult brain (R).
The glymphatic system (the waste clearance system for the nervous system) clears metabolic waste from the mammalian brain while the cerebrospinal fluid removes the beta-amyloid metabolites from the brain (R1, R2).
When individuals sleep well, the glymphatic system can effectively remove cellular waste byproducts that have accumulated outside and inside the brain cells (R).
3) Adequate Sleep Reduces the risk of Heart diseases
Sleep influences cardiovascular function both in healthy people and those with heart diseases (R).
Getting enough quality sleep can reduce cardiovascular risk (R).
Men sleeping 4 hr or less had higher mortality from CHD than those sleeping 7-7.9 hours (R).
Hence short and long self-reported sleep durations are independently associated with a modestly increased risk of coronary heart diseases (R).
4) Sleep Enhances Immune Response
Sleep supports the Initiation of an adaptive Immune response
Mechanism: Sleep presumably enhances lymphocyte proliferation, differentiation, and antibody synthesis.
Sleep also promotes recovery from infectious diseases and lack of sleep increases susceptibility to infections.
5) Sleep Helps Reduce Appetite
In sleep-deprived young men, the decrease in leptin was 18% and an increase in ghrelin was 28% with a total increase in appetite by 23% (R).
6) Sleep May Help with Weight Loss
Insufficient sleep and possibly longer sleep are associated with obesity and eating related problems (R).
National Health and Nutrition Examination Survey (NHANES) analysis showed that adults who slept less than 7hr were more likely to be obese (R).
People who slept only 5.5 hours lost 55% less body fat and 60% more fat-free mass (e.g bones and muscles) compared to people who slept 8.5 hours (R).
Long work hours could contribute to obesity via a reduction in sleep duration in adults (R).
7) Sleep Increases Growth Hormone
The mean GH levels were higher during Slow wave sleep (SWS) compared to other sleep stages (R).
8) Sleep as Neuronal Detoxification process
Note: Neuronal relates to a neuron or neurons (nerve cells).
Effects of Sleep loss
1) Sleep loss and Diabetes risk
In a cohort study men reporting short sleep duration (<or= 5 and 6hr) and long sleep duration (>8hr sleep per night) were twice and more than three times as likely to develop diabetes, respectively (R).
Metabolic pathways linking Sleep disorders with the development of Type 2 diabetes
2) Sleep loss Lowers Testosterone
In a clinical cohort study, men with lower testosterone levels had lower sleep efficiency (R).
3) Sleep Loss May Trigger Autoimmune Diseases
T regulatory cells suppress inappropriate immune and prevent our immune system from attacking our own cells (maintaining self-tolerance) (R). Breakdown of this process can cause autoimmune diseases (R).
Sleep deprivation increases proinflammatory cytokines like IL (interleukin)-1, IL-1β, IL-6, IL-17, and TNF-ɑ.
4) Sleep Loss May Lead to Depression
Sleep disturbances are also commonly associated with other psychiatric illnesses, including (R)
- generalized anxiety disorder
- panic disorder
- posttraumatic stress disorder
5) Sleep Loss Causes Stomach and Bowel Disorders
The ability of the stomach to defend itself against several potential hazards is because of a number of factors which constitute the “gastric mucosal defense” like (R)
- mucus and bicarbonate secreted by surface epithelial cells (neutralize HCl)
- Prostaglandins (act on the stomach wall to inhibit acid secretion)
- gastric mucosal blood flow (protects mucosa by supplying with oxygen and removing H+ and toxins)
- Melatonin secretion (stimulates duodenal bicarbonate secretion, which acts against the HCl discharged from the stomach) (R)
Animal studies have shown that partial sleep deprivation (PSD) compromises gastric mucosal integrity by increasing gastric acidity, blood levels of gastrin, histamine, and noradrenaline and decreasing stomach mucosal blood flow (R).
Hence sleep deprivation damages the stomach and could be one of the risk factors for ulcer formation.
Women who sleep more are less likely to get peptic ulcer disease (R).
A cross-sectional study found a nearly 3-fold increased risk of bowel disorders in patients with insomnia (inability to sleep) (R).
Both extreme short and long duration sleep moderately increased the risk of colorectal cancer in postmenopausal women (R).
6) Poor Sleep May lead to Nonalcoholic Fatty liver Disease (NAFLD)
7) Sleep Duration and Cancer risk
In animal studies sleep deprivation altered proteins associated with the proliferation and apoptosis in carcinogenesis like (R).
- Bcl-2 which prevents the activation of caspases (protease enzymes which help in programmed cell death) and apoptotic process.
- Bax which activates caspases leading to cell death.
- p53 which is a tumor suppressor gene.
Meta-analysis studies suggest a positive association between long sleep duration and colorectal cancer (R).
Less than/equal to 6hr of sleep increases the risk of developing prostate cancer, and sleep greater than/equal to 9 hr has a lower risk (R).
Melatonin prevents tumor initiation, promotion, and progression possibly by (R)
- Its antiproliferative effects (R1, R2).
- Its ability to increase protein 53 (p53), a tumor suppressor protein (R).
- Its capacity to induce cell differentiation (R)
- Its antimetastatic effects (R)
- Its antiangiogenic activity (R)
- Its capacity to decrease telomerase activity (R1, R2)
- functioning as a free radical scavenger (R).
Health Disorders Associated with Sleep Problems
1) Depression and Anxiety
Most depressive disorders patients also have sleep disturbances. Most antidepressant medications suppress rapid eye movement (REM) sleep (R).
Difficulty in initiating or maintaining sleep or both have been reported in about three-quarters of all depressed patients (R).
72.7% of youths with major depression also reported insomnia, and hypersomnia (R).
2) Brain fog
3) Attention-deficit/Hyperactivity Disorder (ADHD)
Sleep problems such as difficulty falling asleep, problem maintaining sleep, poor sleep efficiency, early awakening, and excessive daytime sleepiness is prevalent in patients with cancer (R).
Other Effects of Sleep
Oxidative Stress in Obstructive sleep apnea
Sleep and HPA Axis
The Hypothalamic-pituitary-adrenal axis
Sleep and HPT Axis
The hypothalamus senses low circulating levels of thyroid hormone and respond’s by releasing thyrotropin-releasing hormone (TRH). TRH stimulates the pituitary to produce thyroid-stimulating hormone (TSH). TSH further stimulates the thyroid gland to secrete the thyroid hormones T3 (triiodothyronine) and T4 (thyroxine).
Human sleep inhibits TSH secretion (R).
Sleep and HPG axis
The Hypothalamic-pituitary-gonadal (HPG) axis mainly controls development, reproduction, and aging.
Testosterone levels begin to increase with the onset of sleep and reach a peak at REM sleep (R).
The increase in testosterone with sleep and decrease during time awake is stable for an individual, but in turn, there are individual differences (R).
For example old vs young (aging) since in older men there is an objective difference in the amount of nighttime sleep (R).
Uridine Promotes Sleep
The induction of sleep may be mediated by uridine through uridine receptor in the central nervous system (R).
Uridine binds to the receptors in the areas of the brain which regulate natural sleep.
Uridine, when administered through a systematic route (like intraperitoneally), may pass through the blood-brain barrier to balance sleep (R).
- Cohort studies are a type of medical research used to investigate the cause of disease, establishing links between risk factors and health outcomes.
- A longitudinal study is an observational research method in which data is gathered for the same subjects repeatedly over a period of time.
- Beta amyloids are peptides of 36-43 amino acids that are crucially involved in Alzheimer’s disease (AD) as the main component of the amyloid plaques found in the brain’s of AD patients.
- One potential pathway linking sleep duration and cardiometabolic health is via systemic inflammation (R).
- Hypersomnia or hypersomnolence is a neurological disorder of excessive time spent sleeping or excessive daytime sleepiness (EDS).
- K-complex is an electroencephalography (EEG) waveform that occurs during stage 2 of NREM sleep. It is the largest event in healthy human EEG. They are more frequent in the first sleep cycles.
- A sleep spindle is a burst of oscillatory brain activity visible on the EEG that occurs during stage 2 sleep. It consists of 12-14 Hz waves that occur for at least 0.5 seconds. Sleep spindles are generated in the thalamus of the brain.
- Apoptosis is a genetically regulated cell death involved in the deletion of cells in normal as well as malignant tissues (R).
- Slow wave sleep (SWS) is considered the most restorative stage of sleep where the greatest impact from immune regulation happens.
- During SWS smooth muscles in the colon contract less, so this phase of sleep is considered the “rest period” for the colon.
- So alterations in this phase of sleep can have direct effects on GI (gastrointestinal) physiology (R1, R2).
- Sleep disorders are generally diagnosed using Electroencephalography (EEG) a method used to record the electrical activity of the brain.
- Intraperitoneal means administered through the peritoneum which is a thin transparent membrane that lines the walls of the abdominal cavity that encloses the abdominal organs such as stomach and intestines.