Acute alcohol use leads to sleepiness and promotes sleep onset particularly in lower doses (no more than 1 to 2 drinks per day), but with chronic use at moderate (3 to 7 drinks per day) or greater doses, patients report increasing difficulty falling asleep and staying asleep. Acute alcohol use suppresses REM sleep during the first part of sleep, thereby increasing slow-wave sleep, and reduces sleep latency. Later in sleep, when blood levels of alcohol are falling, REM times and wakefulness are both increased, rebounding from the suppression in the first part of the night. Alcoholism pathophysiology.
In rats with sleep disturbance, low-dose ethanol (1 and 2 g/kg) decreases sleep latency, total wake time, and NREM sleep, whereas there is no effect in rats without sleep disturbance (Obara et al 2010). On a cellular level, Thakkar and colleagues suggest that the sleep promoting effects of ethanol are the result of a decrease in the number of basal forebrain wake-promoting neurons with c-Fos via an mechanism (Thakkar et al 2010, Thakkar et al 2015). Studies exploring underlying neuronal functioning reveal that acute ethanol increases adenosine, and this system plays a role in photic glutamatergic and nonphotic input to the circadian clock. Chronic ethanol consumption leads to downregulated adenosine signaling which underlies insomnia, a major predictor of relapse (Ruby et al 2014).
EEG recordings in rats show increases in 0- to 4-Hz activity accompanying the increase in slow wave sleep, an increase that has not always been found in other animals, and increases in 8- to 13-Hz activity (Young et al 1982). Preclinical studies in mice have also shown that chronic ethanol exposure can disrupt circadian rhythms. In particular, chronic forced ethanol exposure in mice disrupted the timing of locomotor activity and impaired the ability of the circadian clock to phase reset (Seggio et al 2009, Brager et al 2010).
With chronic alcohol use in humans, the alpha pattern commonly occurs along with the delta waves, slow eye movements characteristic of lighter sleep also become pronounced and persist for much of the sleep tracing. Thus, the biological effects of alcohol on sleep paradoxically include concurrent increases in the usual EEG markers of both deep sleep and arousal. Acute alcohol use also increases cerebrospinal fluid cyclic adenosine monophosphate and 5-HIAA in the same patients, showing increased slow wave sleep and decreased REM (Zarcone et al 1980).
Alcohol also has effects on circadian markers in humans. Circadian genes have been found to be related to drinking behaviors. For example, the &ldquo,Per 2&rdquo, gene has been found to regulate alcohol intake in adults (Spanagel 2005a, 2005b) and the &ldquo,Per3&rdquo, gene is associated with both impaired sleep drive and heavy drinking in adolescents (Comasco et al 2010). Mouse models of Per 3 suggest that this period homolog is linked to circadian rhythms, stress response, and alcoholism. When treated with alcohol, there was increased expression of Per 3 in the mouse hippocampus and this interacted with stress response (Wang et al 2012), suggesting that expression of Per 3 may be involved in response to alcohol.
Alcoholic liver pathophysiology
Moderate amounts of alcohol reduce nocturnal melatonin levels in healthy adults (Rupp et al 2007). In substance abusing teens, the time interval between dim light melatonin onset and wake time was significantly and positively related to the Substance Problem Index (SPI), a scale of the severity of substance use (Hasler 2008). In adult male abstinent alcoholics, a lower level of melatonin during the early part of the night and a delay in the nocturnal rise of melatonin (Kuhlwein et al 2003) was found. This finding was supported in a separate study that included male and female subjects (Conroy et al 2012). The alcoholics also demonstrated a slower rate of rise of melatonin secretion in the early part of the night. This lower plasma melatonin level in alcohol dependent patients has also been inversely correlated with intestinal permeability, which may promote endotoxemia, a common consequence of chronic heavy alcohol use (Swanson et al 2015). Moreover, tendency to go to bed late, or being a &ldquo,late chronotype,&rdquo, has been found to be moderated by alcohol drinking and smoking (Wittmann et al 2010). These findings suggest that circadian dysregulation may play a role in the sleep disturbance associated with alcoholism.
The sleepiness associated with alcohol-related sleep disorders occurs both because of the direct sedating effects of the alcohol and because of the arousal occurring during sleep, limiting the restoration of wakefulness. The sedating effects of alcohol are particularly a problem for persons who are already sleepy, either because of a preexisting sleep disorder or because they have chosen to live a moderately sleep-deprived existence. These factors combine to produce significant sleepiness. Alcohol also contributes to impaired judgment about the degree of sleepiness (Lee et al 2015).
For alcoholics and chronic alcohol abusers, early abstinence (Kaplan et al 2014) brings decreased deep sleep, sleep fragmentation, shorter sleep times and, sometimes but not always, increased REM sleep (Allen et al 1971a, 1971b, Gross et al 1973). However, subjective sleep ratings using the Pittsburgh Sleep Quality Index (PSQI) improve early abstinence. This was supported in a sample of alcoholics in a 1 month residential treatment program (p<,.001). Interestingly, only age was associated with improvements in sleep disturbances during this time and not gender, use of hypnotics, hazardous alcohol use, or comorbid psychiatric diagnosis (Kolla et al 2014).
Research has been accumulating to suggest that acute alcohol also affects the homeostatic sleep drive. Sleep EEGs during protracted abstinence show lighter sleep, sleep fragmentation, increased arousal during sleep, and a profound decrease in slow wave sleep, with a gradual recovery occurring at least for some subjects. One study related the decrease in slow-wave sleep and the degree of recovery to the amount of atrophy shown on CT scans during abstinence (Ishibashi et al 1987). Even when undergoing a sleep &ldquo,challenge,&rdquo, ie, staying awake 3 hours later than their typical bedtime, alcoholic men showed a blunted response to the challenge as measured by deep slow-wave activity in the EEG (Brower et al 2011b). Slow-wave activity dissipation across the night in alcohol-dependent men and women showed a blunted SWA response to sleep delay with significantly lower slow-wave activity than the control group (Armitage et al 2012). In an animal model, mice underwent experimentally-induced acute (1 day) and chronic sleep deprivation for (3 days). Acute sleep deprivation resulted in reduced SWA and adenosine tone for at least 2 weeks. Mice that were chronically sleep deprived for 3 days and then tested 24 hours later were less sensitive to the effects of alcohol (Clasadonte et al 2014).
These studies suggest a possible interaction between sleep restriction, alcohol intake, and sleep compensatory mechanisms.
PSG studies suggest that it may require as many as 2 years before normal levels of slow wave sleep are seen in recovering alcoholics, and this may not occur for all subjects (Adamson and Burdick 1973, Wagman and Allen 1975, Rundell et al 1977, Williams and Rundell 1981, Snyder and Karacan 1985, Drummond et al 1998). However, the duration of sobriety, ranging from approximately 1 month to 2 years, did not necessarily predict the level of improvement in EEG spectral power measures over time in a study (Colrain et al 2009). Studies have shown some changes in the electrophysiological components of sleep (eg, amplitude of K complexes, a characteristic of stage 2 sleep) over time in abstinent alcoholics (Colrain et al 2011, 2012). Whether these changes reflect the improvement of sleep over time is still unclear. Other physiological differences have been detected in the sleep of recently recovering alcoholics. For example, reduced heart rate variability, a sign of poor autonomic nervous system functioning, was found in the first part of the night, compared to age and sex matched healthy controls (de Zambotti et al 2014). These lingering effects of alcohol on sleep undoubtedly reflect 1 of the major toxic effects of alcohol on the central nervous system.
The effects of alcohol on the upper airway appear to further enhance the relaxation occurring during sleep, thereby exacerbating obstructive sleep apnea. Alcohol may also exacerbate sleep apnea by blunting chemoreceptor response to blood gases or by raising the arousal threshold. The effects of alcohol on periodic limb movements in sleep are not well established, nor is there any known pathogenesis or pathophysiology for this relationship.