Alcohol and Sleep MCQs PDF

Alcohol and Sleep Alcoholism (AUD) and Sleep • 80 – 90 % of people will consume alcohol at some point in their lifetime • 70 – 80 % reporting consuming alcohol within the previous 12 months. – these rates have remained relatively constant over the past decade in both the United States and Austral...

Alcohol and Sleep Alcoholism (AUD) and Sleep • 80 – 90 % of people will consume alcohol at some point in their lifetime • 70 – 80 % reporting consuming alcohol within the previous 12 months. – these rates have remained relatively constant over the past decade in both the United States and Australia • 4 – 6 % of those will develop an alcohol use or dependence disorder (i.e., alcoholism) • According to the DSM – V (2013) to meet a diagnosis of Alcohol Use Disorder (AUD) an individual must meet at least 2 of 11 criteria (12 months) (same for all substances): – – – – – – – – – – – • exhibit tolerance (require increasing amounts of alcohol to become intoxicated) exhibit withdrawal syndrome (show stress related to NOT consuming alcohol) consume alcohol in larger amounts for longer than intended. have a consistent desire to cut down alcohol use or repeated unsuccessful attempts to do so. spend large amounts of time looking for/obtaining alcohol. miss important events due to consumption. consumption of alcohol is continued despite an understanding of ongoing physical or psychological damage. alcohol craving. recurrent drinking resulting in failure to fulfil role obligations. recurrent drinking in hazardous situations. continued drinking despite alcohol-related social or interpersonal problems Is a continuum: Mild AUD: 2-3 criteria; Moderate AUD: 4-5 criteria; Severe AUD: 6+ criteria However, there is some controversy! Doesn’t consider different patterns of drinking particularly across the life span = young people is more binge drinking (more intense but sporadic) vs older adults drink more consistently across a given week (may be not as much in one sitting). DSM criteria doesn’t allow for this sort of nuance. Ethanol: EtOH • Most consumed form of alcohol is ethyl-alcohol (C2 H5 OH) • Primarily absorbed from the stomach & small intestine • Rapidly passes into the blood stream and reaches maximal blood concentration 30 – 90 min after last ingestion (depending on the conditions present, beverage carbonation – fizzy drinks are absorbed faster, rate of gastric emptying). • It easily crosses the blood brain barrier (and so has effects on the CNS). • Eliminated in several ways:  By direct excretion via the lungs, kidneys, or skin; < 10% kidneys or skin = forms the basis for a breath alcohol test.  Metabolized in the liver via oxidative processes (via enzyme – is a genetic polymorphism in that enzyme which is more prevalent in East Asian people means they have more trouble breaking down Acetalaldehyde – build up can cause nausea; skin redness and general nausea – i.e., is quite toxic, possibly fatal): Ethanol  Acetalaldehyde  Acetyl CoA • Acetyl CoA is either further oxidised or is used in anabolic processes including the production of cholesterol and fatty acids (with possible further ongoing consequences for chronic consumption) EtOH (alcohol) – Effects • Is primarily a central nervous system depressant. o • Despite commonly perceived to be a stimulant – in lower doses it causes a disinhibition and so have feelings of euphoria. The precise mechanism of action of ethanol is not known, but:  Is known to facilitate inhibitory neural pathways that use γ- aminobutyric acid (GABA) as their primary neurotransmitter, probably in a similar fashion to benzodiazepines (sedative hypnotics) via allosteric binding to the GABA receptor (i.e., modifies the GABA receptor and enhance the inhibitory action of the endogenous GABA).  It also inhibits excitatory pathways that use glutamate – the primary excitatory neurotransmitter in the CNS - (but not known whether this effect is direct or indirect EtOH – Acute Effects • The acute effects of alcohol consumption can be influenced by several factors including: o o o • dose or presence of other drugs (reciprocal enhancement) stress levels (effect rate of absorption and behavioural effects) even levels of sleep deprivation (if sleep deprived will experience effects of alcohol at lower doses and potentially for longer periods of time) Effects at low to moderate doses: o o Behavioral disinhibition, psychomotor impairment and potentially some cognitive impairment Physiological effects: reflexive increase in heart rate caused by peripheral vasodilation. • Effects at high dose levels: o Widespread depression in CNS activity leading to a loss of motor control, sedation, narcosis and ultimately death from respiratory suppression (very high doses but if have another drug on board – benzo or sedatives - then commonly see overdoses). o Wide range of individual differences in tolerance levels of alcohol. EtOH – Chronic Effects • Chronic alcohol consumption can lead to significantly increased morbidity, mortality & disability. • With increased risk for developing other chronic diseases including: o o o o o o • Mouth, esophageal & liver cancers Depression/anxiety Epilepsy A range of cardiovascular diseases Cirrhosis of the liver Diabetes Finally, the brain can be affected at both a structural and functional level by chronic alcohol consumption. EtOH – Chronic CNS Effects • Chronic excessive alcohol consumption has been associated with alterations in cortical and sub-cortical grey matter and white matter. • Postmortem studies of brain morphology: tend to show greater white than grey matter reductions most notably loss in the frontal cortex. • In vivo studies: MRI data are generally consistent with the neuropathological studies but typically report similar extents of both grey matter and white matter volume reduction within the cortex. • As observed postmortem, MRI studies report that the greatest loss of cortex occurs in the frontal lobes. Both AUD groups have reduced grey matter volumes across large areas of the brain – more prominent in frontal areas – more exacerbated in the older age group – perhaps due to longer drinking history but also have the normal agerelated effects upon cortical volume A widening of the sulci and gyri – indicating the loss of grey and white matter. Larger lateral ventricles. Major structural brain changes – difference was the amount of alcohol consumed over their lifetime. Lifetime alcohol consumption estimates: • Control EtOH consumption ~ 240 kgs of pure alcohol (1085 bottles of 40% spirit) • AUD EtOH consumption ~ 1254 kgs of pure alcohol (5675 bottles of 40% spirit) EtOH – Sleep Effects • Alcohol can have a large impact on central nervous system function. • One main function that can be disrupted is that of sleep. o Acute effects - usually pharmacological/physiological effects on sleep o Effects of chronic excessive alcohol consumption - can be due to both pharmacological / physiological factors and structural brain changes. EtOH – Sleep Effects in Alcoholics • Alcoholics tend to have a wide range of sleep disturbances, including: o  frequency of awakenings - more fragmented sleep o  REM o  SWS o significant levels of insomnia (trouble getting to sleep and maintaining sleep  this is when sober. • Studies from the late 70’s – early 80’s administered alcohol to alcoholics in inpatient treatment facilities prior to withdrawal and treatment to investigate the acute effects of alcohol in alcoholics showing: o  SWS o  REM sleep (compared to their own baseline) • This is consistent with what is seen in acute administration studies in non-alcoholic individuals. • One difference was that alcoholics exhibited increased rather than a decreased sleep onset latency possibly due to tolerance effects. o • Non-AUD’s tend to fall asleep faster after consuming alcohol. Studies that have looked at sleep in alcoholics during the early post-withdrawal phase (~2 – 6 weeks abstinence) generally found (all relative to baseline): o o o o o o  SWS  sleep efficiency (proportion of time asleep compared to time in bed)  total sleep time  stage one sleep (transitional light non-REM sleep)  REM sleep  sleep onset latency (took longer to fall asleep) • Longer term follow-up studies (up to ~ 1.5 years abstinence) have demonstrated similar patterns of results, although sleep onset latency and total sleep time tended to return towards normal. Seems to be some functional recovery. • Studies extending out to three years abstinence are less consistent but generally report: o o •  SWS compared to controls but within “normal” limits. Sleep fragmentation: results are equivocal - REM sleep effects tend to be variable but generally increased REM pressure - i.e., go into REM sleep earlier in the night so have reduced REM onset latency. A meta-analysis of eight studies of sleep changes in alcoholic men showed substantial reductions in SWS as the most consistent finding. Why is this of interest? • SWS (quantity and intensity) has been used as a marker of sleep quality (i.e., the more SWS the more restorative we believe sleep to be) and may serve as a good measure of alcohol related brain damage. • Sleep quality, particularly SWS, is a strong predictor of likelihood of relapse in abstinent alcoholics. • Thus, using simple measures of sleep, we may be able to investigate both alcohol-related brain damage and early markers of relapse risk. SWS & Delta Activity • Stages 3 and 4 sleep (together comprise SWS) are characterized by delta activity. • From animal studies, it has been shown that to generate high amplitude, low frequency delta EEG activity, a highly structurally and functionally intact cerebral cortex is required. Need lots of neurons firing at once to get the recording. SWS: slow – gaps between peaks and amplitude – the distance between one peak and the next compared to other stages of sleep and wakefulness What if we wanted to try and examine the degree of neuronal disruption by looking at slow wave activity? We need a discrete measure of cortical synchronisation! K-complexes and N550s In Stage 2 of non-REM sleep there are K complexes: can be thought of as an isolated delta wave that occurs spontaneously during N2 sleep and can be evoked using sound - and sleep spindles The K-complex • Some controversy in literature over the function of the k-complex i.e., what is its purpose in sleep structure? o Arousal response (given they occur in response to external stimuli - the brain waking up a bit) vs. o • Nicholas, Trinder and Colrain (2002): Brought participants into lab for 3 consecutive nights to look at K-complex production after a night of fragmented sleep. o o o o • Sleep Maintenance response - it occurs due to potentially disruptive stimulus, but the brain needs to try to maintain the continuity of sleep and so produces a kcomplex to dampen down any arousal activity. 1st night recorded k-complexes after playing tones 2nd night gave them a very bad night’s sleep – waking them up one to 2 minutes over the night (highly fragmented) 3rd night - looked at k-complexes again. If k-complexes were an arousal response, would expect to see less of them after a fragmented sleep (as more tired) whereas if they are asleep protective response the body will want to make sure get a lot of sleep and so would expect to see more k-complexes. Found an increase in proportion of k-complexes following sleep fragmentation – supporting the sleep maintenance hypothesis. Cash et al (2009): Other cortical oscillations – one called the “slow oscillation” which can see in individual neurons and in populations of neurons - argued the k-complex represents the down state (or the quiescent state) of the cortical slow oscillation – supporting idea that they act to dampen down cortical activity. • Other studies have shown k-complexes to be the forerunner of slow wave sleep. So as progress through stage 2 towards SWS, start to get more k-complexes and are easier to evoke prior to going into SWS compared to before going into REM sleep. o De Gennaro et al. (2000); Nicholas et al (2006) • A discrete instance of slow wave activity. • Although the exact generator of K-complexes is not clear it appears to be very similar to the generation of Slow Wave activity. • The K-complex has a characteristic waveform/shape when evoked by a stimulus (tones) during sleep. o o o It shows a small negativity (N350) followed by a large negativity (N550) followed by a large positivity (P900) Zero is the time the sound is presented N550: is the peak - is from a frontal electrode – the average k-complex is much bigger in amplitude over the frontal region N300 is from a central electrode i.e., at top of head The N550: the peak of the K-complex • The N550 is the large negative potential of an evoked K-complex that occurs at around 550 ms after the stimulus (~1/2 a second) • The K-complex has the same topographical distribution as the N550. • The K-complex has been found to contribute exclusively to the N550 potential – if the average of tones does not evoke a K-complex, there’s no N550 but if average tones do evoke a K-complex, will be an N550 (the large negative wave form). • Bastien et al. (2002): therefore, assert that N550 is a measure of the “pure” KComplex (gets rid of any background “noise”). So, is reduced K-complex activity linked to cortical disruption? Can we show that if there is cortical disruption, there will be reduced K-complexes? Aging and the N550 • • Crowley, Trinder and Colrain (2002): young vs older adults o Study of K-Complex amplitude and frequency of occurrence in younger vs elderly o Found older people had fewer and smaller K-complexes and N550s Colrain, Crowley, Nicholas, Afifi et al (2010): across the adult lifespan (18 – 80s) o K-complexes and N550 amplitude decreased linearly with age. Alcoholism and the N550 • • Nicholas, Sullivan, Pfefferbaum, Trinder and Colrain (2002) o Study of K-complexes and N550 amplitude in middle-aged alcoholics compared to well matched controls. o Showed AUD patients had fewer and smaller K-complexes (or N550s) Colrain et al (2009) o Larger study of EEGs of 84 men and women, 42 alcoholics Is a negative voltage so the more negative number (lower on graph) means greater N550. White dots are controls. Red diamonds = AUD Solid line is regression for controls and 2 dotted lines are 1 and 2 standard deviations smaller than controls. Virtually all AUD patients were showing smaller N550s than their age counterpart controls. Their sleep made them look ~23 years older The K-complex as a measure of CNS integrity • The K-Complex is a highly synchronized EEG event. • Shows the ability of the brain neurons to synchronize to fire off at the same time. • Disruption in cortical matter, particularly grey matter, will lead to decreased synchronization (or ability of the brain to talk to itself). • Therefore, the presence, timing and amplitude of the K-complex all provide functional measures of CNS integrity. Can these techniques be used to investigate early effects of alcohol use on sleep? Why look at effect of alcohol use on sleep in adolescents and young adults? • Most studies on alcoholism involve adults, or middle-aged people who are being treated for alcoholism. • Despite the wide range of literature about the effects of alcoholism on the brain, there is relatively little research on binge drinking and effects of different patterns across the lifespan. • Binge drinking is common in adolescent college students in both the US and Australia (Weschler 1994; 2000). • Studying adolescent binge drinkers will allow us to: o observe the effects of alcohol on the CNS integrity independent of the effects of alcoholism in the treated population. o observe the effects of alcohol on CNS integrity independent of aging. How? • Recruited binge drinkers and non-binge drinking adolescents. • Recording polysomnography on 2 nights of sleep (one with acute alcohol consumption to reach a peak of 0.09% BAC and one with a placebo) in the lab • Examining K-complex incidence and N550 amplitude to see if there’s a difference between binge drinking vs. non binge drinking adolescents. The Effects of Binge Drinking on the N550 in Adolescents Honours Projects • Recruiting heavy/binge drinkers and non-binge drinking 18–21-year-olds. o 10 Heavy drinkers (96.9 ± 48.6 drinks in the previous month – majority done over 3 nights a week – ie short heavy periods of drinking) o • 9 Light drinkers (9.5 ± 7.9 drinks in the previous month) Examine K-complex incidence and N550 amplitude before and after consumption to see if there’s a difference between binge drinking vs. non binge drinking and if there are any differences in these measures after acute alcohol consumption. Results: Heavy drinkers produced fewer evoked K-complexes in both alcohol and placebo conditions. Ability to produce K-complexes was reduced. Solid lines: heavy drinkers Dashed lines: light drinkers In stage 2 sleep – no difference in amplitude between groups and across conditions SWS – slight difference between alcohol and placebo conditions – don’t know why Conclusions: • The data are consistent with previous studies indicating that the KC is an all or none event (i.e., they either happen or they don’t) • Some of the changes in KC generation seen in abstinent chronic alcoholics (i.e., less KCs and lower 550 amplitude) are already evident in heavy drinking young adults. So what about alcohol’s effects on traditional sleep measures in adolescents & young adults more generally: looking at same group Adolescent Sleep • Adolescents show marked reductions in SWS and EEG delta frequency across adolescence starting with a rapid decrease in early teens to late teens and then more gradual decrease into early to mid 20s. • Associated with: o reduced homeostatic sleep drive - want to go to bed later and sleep in longer o Circadian phase delay • • Shift to later bedtime Shortened sleep duration (as most must get up to go to school or work) but are going to bed later. Adolescent Development • Profound neurodevelopment effects which exhibit themselves across adolescence as decrease in grey matter volumes (or synaptic density) and increase in white matter (reinforcing the speed of the neural tracks). • i.e., synaptic density decreases in grey matter with synaptic pruning, increase in white matter. Last areas to complete neurodevelopment are the frontal and pre-frontal cortex. Another study looked at several physiological measures: all following the same pattern.  a peak in mid-childhood a dramatic decrease into adolescence and levels out post 25 Alcohol Use in Adolescence • Adolescence coincides with onset of alcohol use • 90% of Australian university students - 43% reported binge drinking. • Because such an important time of brain development there is increased susceptibility to alcohol’s neurotoxicity • The converse argument is that because of the brain’s plasticity during adolescence, there is greater potential for recovery. Acute Alcohol Ingestion in Adults What happens when drink alcohol before going to bed: • Reduced sleep onset latency (so fall asleep faster). Then: o o 1st half of night – more SWS; fewer arousals 2nd half of night - more arousals, decreased sleep efficiency (ie more arousals and awakenings), less SWS - marked disturbance • Argued that 1st half of night is a consolidation of sleep (often emphasized due to the increased SWS and Delta EEG spectral power) • Tolerance effect: the longer people drink for, the smaller the differences are. What about in this younger age group? Only two studies have looked at this at an acute level: Acute Alcohol Ingestion in Late Adolescence (all light drinkers) Williams, Maclean and Cairns (1983); Chan et al., ( 2013 Found similar patterns as observed in adults: • 1st half of night: same consolidatory effect: o ↑ SWS, ↓ Arousals o ↑ N-REM delta & alpha EEG spectral power (Chan, 2013) o Consolidation effects are often emphasized largely due to increased SWS & delta EEG spectral power. • 2nd half of night: increased disturbance: o ↓ SWS, ↑ WASO (wakefulness after sleep), ↓ Sleep efficiency o marked disturbance • But did NOT see a reduced sleep onset latency compared to placebo (Chan et al., 2013) • Extra finding: drastic changes between conditions in N-REM delta and alpha EEG spectral power (Chan, Colrain, Trinder & Nicholas, 2013). Amplitude of SWS is bigger and is more frequent in the alcohol condition. Can also see burst of high frequency EEG activity. When decompose it can see increase in delta and alpha power in the alcohol condition (which is predominantly seen in quiet wakefulness). • Alpha-delta sleep is typically seen in chronic pain condition and so it has been argued that this indicates a particularly disruptive stimuli present during sleep. Alcohol dependency and Sleep in Adults • ↑ sleep disturbance and sleep disorders • ↑ Sleep Onset Latency: less total sleep time • ↓ SWS and ↓ K-complexes • ↑ REM sleep pressure: ↑ REM %, ↑ REM density, ↓ REM onset • Reduced SWS and increased REM sleep pressure is predictive of relapse. • Reduced SWS and reduced K-complexes reflect reduced cortical integrity particularly in the frontal regions of the brain. Heavy Alcohol Use in Adolescents Why might this be important? • Frontal brain regions predisposed to alcohol related damage. • Final area to develop in adolescence – so might be more compromised. • Heightened neurotoxic effects of alcohol. Animal Models Enduring changes in functional brain activity particularly during sleep in chronically exposed rats: o large reductions in SWS o EEG spectral power; large reduction in NREM delta activity (Criado, Wills, Walker, & Ehlers, 2008; Ehlers, Desikan, & Wills, 2013 Humans Studies looking at heavy alcohol use in adolescents have shown: • Differential functional connectivity during wakefulness (de Bruin et al., 2004) • Deterioration in neural functioning, including memory and learning impairments, in young people diagnosed with alcohol use disorders (Zeigler et al., 2005) • Non-REM sleep K-complex incidence is reduced in heavy drinking late adolescents not meeting diagnostic criteria for AUDs (Nicholas et al., 2011) Summary Adolescence is a critical time: • Neurodevelopment • Development of sleep regulatory systems • Coincides with onset of alcohol use ➢ Potentially neurotoxic effects of alcohol We know that: • normal sleep is fundamental to healthy development. • measures of normal sleep are reflective of cortical integrity. • acute and chronic alcohol exposure may affect the developing brain and sleep systems differentially to adults. • this could have important consequences for health and broader development. Final Study – Caitlyn Gourlay PhD work Aim: to investigate the acute and chronic effects of alcohol ingestion on objective sleep measures in late adolescents (18 to 21 years) and compare sex differences. Light Drinkers: < 7 SD per week on average, no more than 2 occasions > 4 SD in one sitting in the previous 30 days (to eliminate regular bingeing) Heavy Drinkers: > 14 SD per week in at least 2 of the previous 4 weeks and > 4 SD may be consumed in one sitting on multiple occasions in the previous 30 days. Procedure: • No alcohol 48 hours • No caffeine or food after lunch time • Maintain normal sleep-wake schedule • 3 non-consecutive nights in lab:  1st night adaptation  2nd night alcohol (targeted so reach peak BAC 30-45 minutes of sleep)  3rd night placebo Measured variables 1. Sleep quality & macro sleep-architecture variables (SOL, Total Sleep Time, % of REM, N1, N2, & SWS, sleep efficiency, WASO, and arousals) - using standard diagnostic AASM criteria 2. Micro sleep-architecture variables (spectral power analysis of the five main EEG frequency bands; alpha, beta, theta, sigma, and delta) n gender HEAVY DRINKERS 10 2 female LIGHT DRINKERS 9 4 female age 19.6 ± 1.1 yrs 19.8 ± 1.2 yrs 30-day alcohol* 125.9 ± 88.2 13.1 ± 8.5 * standard drinks (10 grams of alcohol) By design, groups differed on drinking history in the previous month (p=.003) but did not differ in age, BMI or age drinking was initiated (p>.05). Results Mean SWS% for heavy and light drinkers in placebo condition across first four sleep cycles. *p < .001 ** Heavy drinkers had less SWS in the placebo condition Heavy Drinkers Light Drinkers Mean REM% for heavy and light drinkers in placebo condition across first four sleep cycles. *p=.032 Heavy drinkers had slightly more REM sleep in the placebo condition Heavy Drinkers Light Drinkers Potential explanations: • Sleep differences might precede alcohol use (some differences that predispose to heavier use of alcohol) • Or alcohol related structural and functional brain changes. • Or adaptation of neurotransmitter systems • Or due to alcohol withdrawal effects (≥48 hours abstinence) Acute alcohol versus placebo in Adolescence BAC @ LIGHTS OUT ALCOHOL 0.081 ± 0.02% PLACEBO 0.0% Following pre-bedtime alcohol ingestion: • Both groups show a decrease in total REM % compared to placebo condition (p <.01) • No differences in SOL, TST, TIB (p >.05) • Both groups exhibited the expected sleep cycle related changes: more SWS in 1st half of night and less SWS (p =.001) and increases in REM sleep (p =.001) in 2nd half of night across both conditions. However: mean SWS% in heavy and light drinkers for alcohol and placebo condition across first four sleep cycles. Alcohol condition by group interaction, p=.016. Heavy drinkers increased SWS after alcohol consumption whereas light drinkers decreased SWS in alcohol condition: an unexpected result Recording cuts out here Potential explanations: • Sleep differences precede alcohol use • Adaptation of neurotransmitter systems to the presence of acute alcohol Conclusions Heavy drinking late adolescents show similar sleep abnormalities to long-term alcohol dependent individuals:  ↓ SWS, ↑ REM  ↑ SWS following pre-bedtime alcohol As the adolescent brain is not fully formed before the onset of alcohol use, it’s chronic and acute consumption may interfere with neural development in such a way that it’s effects may be permanent. In turn, the adolescent brain may show greater potential for recovery as brain composition is not yet ‘fixed’.