rapid eye movement sleep (rem) deprivation may alleviate clinical depression because it mimics selective serotonin reuptake inhibitors (ssris). this is because the natural decrease in monoamines during rem is not allowed to occur, which causes the concentration of neurotransmitters in the brain, that are depleted in clinically depressed persons, to increase. lasting rem sleep deprivation causes swollen mitochondrias in neurons (caused by cytochrome c); noradrenaline receptor blocker keeps its inner cristae intact. studies on rodents show that response to neuronal injury due to acute sleep deprivation and is adaptative before 3 hours of sleep loss per night and becomes maladaptative and apoptosis occurs after. studies in mice show neuronal death (in the hippocampus, locus coeruleus and medial pfc) occurs after 2 days of rem sleep deprivation. however, mice do not model well the effects in humans because they sleep a third of the duration of rem sleep of humans and caspase-3, the main effector of apoptosis, kills 3 times the amount of cells in humans than in mice. also not accounted in nearly all of the studies is that acute rem sleep deprivation induces lasting (> 20 days) neuronal apoptosis in mice, and apoptosis rate increases on the day following its end, so the amount of apoptosis is often undercounted in mice because experiments nearly always measure it the day the sleep deprivation ends. for these reasons, both the time before cells degenerate and the extent of degeneration could be greatly underevaluated in humans. such histological studies cannot be performed on humans for ethical reasons, but long-term studies show that sleep quality is more associated to grey matter volume reduction than age, occurring in areas like the precuneus. molecular pathway of rem sleep deprivation induced apoptosis in neurons sleep is necessary to repair cellular damage, such as caused by reactive oxygen species and dna damages. during long-term sleep deprivation, cellular damage aggregates up to a tipping point that triggers cellular degeneration and apoptosis. rem sleep deprivation causes an increase in noradrenaline (which incidentally causes the person sleep deprived to be stressed) due to the neurons in the locus coeruleus producing it not ceasing to do so, which causes an increase in the activity of the na⁺/k⁺-atpase pump, which itself activates the intrinsic pathway of apoptosis and prevents autophagy, which also induces the mitochondrial pathway of apoptosis. sleep outside of the rem phase may allow enzymes to repair brain cell damage caused by free radicals. high metabolic activity while awake damages the enzymes themselves preventing efficient repair. this study observed the first evidence of brain damage in rats as a direct result of sleep deprivation. attention and working memory among the possible physical consequences of sleep deprivation, deficits in attention and working memory are perhaps the most important; such lapses in mundane routines can lead to unfortunate results, from forgetting ingredients while cooking to missing a sentence while taking notes. performing tasks that require attention appears to be correlated with number of hours of sleep received each night, declining as a function of hours of sleep deprivation. working memory is tested by methods such as choice-reaction time tasks. the attentional lapses also extend into more critical domains in which the consequences can be life-or-death; car crashes and industrial disasters can result from inattentiveness attributable to sleep deprivation. to empirically measure the magnitude of attention deficits, researchers typically employ the psychomotor vigilance task (pvt) which requires the subject to press a button in response to a light at random intervals. failure to press the button in response to the stimulus (light) is recorded as an error, attributable to the microsleeps that occur as a product of sleep deprivation. crucially, individuals' subjective evaluations of their fatigue often do not predict actual performance on the pvt. while totally sleep-deprived individuals are usually aware of the degree of their impairment, lapses from chronic (lesser) sleep deprivation can build up over time so that they are equal in number and severity to the lapses occurring from total (acute) sleep deprivation. chronically sleep-deprived people, however, continue to rate themselves considerably less impaired than totally sleep-deprived participants. since people usually evaluate their capability on tasks like driving subjectively, their evaluations may lead them to the false conclusion that they can perform tasks that require constant attention when their abilities are in fact impaired. mood sleep deprivation can have a negative impact on mood. staying up all night or taking an unexpected night shift can make one feel irritable. once one catches up on sleep, one's mood will often return to baseline or normal. even partial sleep deprivation can have a significant impact on mood. in one study, subjects reported increased sleepiness, fatigue, confusion, tension, and total mood disturbance, which all recovered to their baseline after one to two full nights of sleep. depression and sleep are in a bidirectional relationship. poor sleep can lead to development of depression and depression can cause insomnia, hypersomnia, or obstructive sleep apnea. about 75% of adult patients with depression can present insomnia. sleep deprivation, whether total or not, can induce significant anxiety and longer sleep deprivations tend to result in increased level of anxiety. sleep deprivation has also shown some positive effects on mood, and can be used to treat depression. chronotype can affect how sleep deprivation influences mood. those with morningness (advanced sleep period or "lark") preference become more depressed after sleep deprivation while those with eveningness (delayed sleep period or "owl") preference show an improvement in mood. mood and mental states can affect sleep as well. increased agitation and arousal from anxiety or stress can keep one more aroused, awake, and alert. driving ability main article: sleep-deprived driving the dangers of sleep deprivation are apparent on the road; the american academy of sleep medicine (aasm) reports that one in every five serious motor vehicle injuries is related to driver fatigue, with 80,000 drivers falling asleep behind the wheel every day and 250,000 accidents every year related to sleep, though the national highway traffic safety administration suggests the figure for traffic accidents may be closer to 100,000. the aasm recommends pulling off the road and taking a 15- or 20-minute nap to alleviate drowsiness. according to a 2000 study published in the british medical journal, researchers in australia and new zealand reported that sleep deprivation can have some of the same hazardous effects as being drunk. people who drove after being awake for 17–19 hours performed worse than those with a blood alcohol level of 0.05 percent, which is the legal limit for drunk driving in most western european countries and australia. another study suggested that performance begins to degrade after 16 hours awake, and 21 hours awake was equivalent to a blood alcohol content of 0.08 percent, which is the blood alcohol limit for drunk driving in canada, the u.s., and the u.k. fatigue of drivers of goods trucks and passenger vehicles have come to the attention of authorities in many countries, where specific laws have been introduced with the aim of reducing the risk of traffic accidents due to driver fatigue. rules concerning minimum break lengths, maximum shift lengths and minimum time between shifts are common in the driving regulations used in different countries and regions, such as the drivers' working hours regulations in the european union and hours of service regulations in the united states. the exxon valdez oil spill was the second largest oil spill in the united states waters, after the 2010 deepwater horizon oil spill. this accident occurred when an exxon oil tanker struck a reef at the prince william sound in alaska. approximately 10.8 million gallons of oil spilled into the sea. the accident caused great environmental damage including the death of hundreds of thousands of birds and sea creatures. fatigue and sleep deprivation were the major contributors to the accident. the captain of the ship was asleep after a night of heavy drinking; he was severely fatigued and had been awake for 18 hours. the entire crew was suffering from fatigue and inadequate sleep. sleep transition sleep propensity (sp) can be defined as the readiness to transit from wakefulness to sleep, or the ability to stay asleep if already sleeping. sleep deprivation increases this propensity, which can be measured by polysomnography (psg), as a reduction in sleep latency (the time needed to fall asleep). an indicator of sleep propensity can also be seen in the shortening of transition from light stages of non-rem sleep to deeper slow-waves oscillations can also be measured as indicator of sleep propensity. on average, the latency in healthy adults decreases by a few minutes after a night without sleep, and the latency from sleep onset to slow-wave sleep is halved. sleep latency is generally measured with the multiple sleep latency test (mslt). in contrast, the maintenance of wakefulness test (mwt) also uses sleep latency, but this time as a measure of the capacity of the participants to stay awake (when asked to) instead of falling asleep. sleep-wake cycle people aged 18 to 64 need seven to nine hours of sleep per night. research studying sleep deprivation shows its impact on mood, cognitive and motor functioning, due to dysregulation of the sleep-wake cycle and augmented sleep propensity. multiple studies that identified the role of the hypothalamus and multiple neural systems controlling circadian rhythms and homeostasis have been helpful in understanding sleep deprivation better. to describe the temporal course of the sleep-wake cycle, the two-process model of sleep regulation can be mentioned. this model proposes a homeostatic process (process s) and a circadian process (process c) that interact to define the time and intensity of sleep. process s represents the drive for sleep, increasing during wakefulness and decreasing during sleep, until a defined threshold level, while process c is the oscillator responsible for these levels. when being sleep deprived, homeostatic pressure accumulates to the point that waking functions will be degraded even at the highest circadian drive for wakefulness. microsleeps microsleeps are periods of brief sleep that most frequently occur when a person has a significant level of sleep deprivation. microsleeps usually last for a few seconds, usually no longer than 15 seconds, and happen most frequently when a person is trying to stay awake when they are feeling sleepy. the person usually falls into microsleep while doing a monotonous task like driving, reading a book, or staring at a computer. microsleeps are similar to blackouts and a person experiencing them is not consciously aware that they are occurring. an even lighter type of sleep has been seen in rats that have been kept awake for long periods of time. in a process known as local sleep, specific localized brain regions went into periods of short (~80 ms) but frequent (~40/min) nrem-like states. despite the on and off periods where neurons shut off, the rats appeared to be awake, although they performed poorly at tests. cardiovascular morbidity decreased sleep duration is associated with many adverse cardiovascular consequences. the american heart association has stated that sleep restriction is a risk factor for adverse cardiometabolic profiles and outcomes. the organization recommends healthy sleep habits for ideal cardiac health along with other well known factors like blood pressure, cholesterol, diet, glucose, weight, smoking, and physical activity. the centers for disease control and prevention has noted that adults who sleep less than 7 hours per day are more likely to have chronic health conditions including heart attack, coronary heart disease, and stroke compared to those with adequate amount of sleep. in a study that followed over 160,000 healthy, non-obese adults, the subjects who self-reported sleep duration less than 6 hours a day were at an increased risk for developing multiple cardiometabolic risk factors. they presented with increased central obesity, elevated fasting glucose, hypertension, low high-density lipoprotein, hypertriglyceridemia, and metabolic syndrome. the presence or lack of insomnia symptoms did not modify the effects of sleep duration in this study. the united kingdom biobank studied nearly 500,000 adults who had no cardiovascular disease, and the subjects who slept less than 6 hours a day were associated with a 20 percent increase in the risk of developing myocardial infarction (mi) over 7 years of follow-up period. interestingly, long sleep duration of more than 9 hours a night was also a risk factor. immunosuppression among the myriad of health consequences that sleep deprivation can cause, disruption