Effects of sex, age, and body mass index on serum bicarbonate.

Rationale: Obesity hypoventilation syndrome (OHS) is often underdiagnosed, with significant morbidity and mortality. Bicarbonate, as a surrogate of arterial carbon dioxide, has been proposed as a screening tool for OHS. Understanding the predictors of serum bicarbonate could provide insights into risk factors for OHS. We hypothesized that the bicarbonate levels would increase with an increase in body mass index (BMI), since the prevalence of OHS increases with obesity. Methods: We used the TriNetX Research Network, an electronic health record database with de-identified clinical data from participating healthcare organizations across the United States, to identify 93,320 adults without pulmonary or advanced renal diseases who had serum bicarbonate and BMI measurements within 6 months of each other between 2017 and 2022. We used linear regression analysis to examine the associations between bicarbonate and BMI, age, and their interactions for the entire cohort and stratified by sex. We also applied a non-linear machine learning algorithm (XGBoost) to examine the relative importance of age, BMI, sex, race/ethnicity, and obstructive sleep apnea (OSA) status on bicarbonate. Results: This cohort population was 56% women and 72% white and 80% non-Hispanic individuals, with an average (SD) age of 49.4 (17.9) years and a BMI of 29.1 (6.1) kg/m2. The mean bicarbonate was 24.8 (2.8) mmol/L, with higher levels in men (mean 25.2 mmol/L) than in women (mean 24.4 mmol/L). We found a small negative association between bicarbonate and BMI, with an expected change of -0.03 mmol/L in bicarbonate for each 1 kg/m2 increase in BMI (p < 0.001), in the entire cohort and both sexes. We found sex differences in the bicarbonate trajectory with age, with women exhibiting lower bicarbonate values than men until age 50, after which the bicarbonate levels were modestly higher. The non-linear machine learning algorithm similarly revealed that age and sex played larger roles in determining bicarbonate levels than the BMI or OSA status. Conclusion: Contrary to our hypothesis, BMI is not associated with elevated bicarbonate levels, and age modifies the impact of sex on bicarbonate.

Fetal heart rate responses to maternal sleep-disordered breathing.

BACKGROUND: Maternal sleep-disordered breathing is associated with adverse pregnancy outcomes and is considered to be deleterious to the developing fetus. Maternal obesity potentiates sleep-disordered breathing, which, in turn, may contribute to the effect of maternal obesity on adverse fetal outcomes. However, only a few empirical studies have evaluated the contemporaneous effects of maternal sleep-disordered breathing events on fetal well-being. These events include apnea and hypopnea with accompanying desaturations in oxyhemoglobin. OBJECTIVE: This study aimed to reconcile contradictory findings on the associations between maternal apnea or hypopnea events and clinical indicators of fetal compromise. It also sought to broaden the knowledge base by examining the fetal heart rate and heart rate variability before, during, and after episodes of maternal apnea or hypopnea. To accomplish this, we employed overnight polysomnography, the gold standard for ascertaining maternal sleep-disordered breathing, and synchronized it with continuous fetal electrocardiography. STUDY DESIGN: A total of 84 pregnant women with obesity (body mass index >30 kg/m2) participated in laboratory-based polysomnography with digitized fetal electrocardiography recordings during or near 36 weeks of gestation. Sleep was recorded, on average, for 7 hours. Decelerations in fetal heart rate were identified. Fetal heart rate and heart rate variability were quantified before, during, and after each apnea or hypopnea event. Event-level intensity (desaturation magnitude, duration, and nadir O2 saturation level) and person-level characteristics based on the full overnight recording (apnea-hypopnea index, mean O2 saturation, and O2 saturation variability) were analyzed as potential moderators using linear mixed effects models. RESULTS: A total of 2936 sleep-disordered breathing events were identified, distributed among all but 2 participants. On average, participants exhibited 8.7 episodes of apnea or hypopnea per hour (mean desaturation duration, 19.1 seconds; mean O2 saturation nadir, 86.6% per episode); nearly half (n=39) of the participants met the criteria for obstructive sleep apnea. Only 45 of 2936 apnea or hypopnea events were followed by decelerations (1.5%). Conversely, most (n=333, 88%) of the 378 observed decelerations, including the prolonged ones, did not follow an apnea or a hypopnea event. Maternal sleep-disordered breathing burden, body mass index, and fetal sex were unrelated to the number of decelerations. Fetal heart rate variability increased during events of maternal apnea or hypopnea but returned to initial levels soon thereafter. There was a dose-response association between the size of the increase in fetal heart rate variability and the maternal apnea-hypopnea index, event duration, and desaturation depth. Longer desaturations were associated with a decreased likelihood of the variability returning to baseline levels after the event. The mean fetal heart rate did not change during episodes of maternal apnea or hypopnea. CONCLUSION: Episodes of maternal sleep apnea and hypopnea did not evoke decelerations in the fetal heart rate despite the predisposing risk factors that accompany maternal obesity. The significance of the modest transitory increase in fetal heart rate variability in response to apnea and hypopnea episodes is not clear but may reflect compensatory, delimited autonomic responses to momentarily adverse conditions. This study found no evidence that episodes of maternal sleep-disordered breathing pose an immediate threat, as reflected in fetal heart rate responses, to the near-term fetus.

D-dimer in Marfan syndrome: effect of obstructive sleep apnea induced blood pressure surges.

Aortic dissection and rupture are the major causes of premature death in persons with Marfan syndrome (MFS), a rare genetic disorder featuring cardiovascular, skeletal, and ocular impairments. We and others have found that obstructive sleep apnea (OSA) confers significant vascular stress in this population and may accelerate aortic disease progression. We hypothesized that D-dimer, a diagnostic biomarker for several types of vascular injury that is also elevated in persons with MFS with aortic enlargement, may be sensitive to cardiovascular stresses caused by OSA. To test this concept, we recruited 16 persons with MFS without aortic dissection and randomized them to two nights of polysomnography, without (baseline) and with OSA treatment: continuous positive airway pressure (CPAP). In addition to scoring OSA by the apnea-hypopnea index (AHI), beat-by-beat systolic BP (SBP) and pulse-pressure (PP) fluctuations were quantified. Morning blood samples were also assayed for D-dimer levels. In this cohort (male:female, 10:6; age, 36 ± 13 yr; aortic diameter, 4 ± 1 cm), CPAP eliminated OSA (AHI: 20 ± 17 vs. 3 ± 2 events/h, P = 0.001) and decreased fluctuations in SBP (13 ± 4 vs. 9 ± 3 mmHg, P = 0.011) and PP (7 ± 2 vs. 5 ± 2 mmHg, P = 0.013). CPAP also reduced D-dimer levels from 1,108 ± 656 to 882 ± 532 ng/mL (P = 0.023). Linear regression revealed a positive association between the maximum PP during OSA and D-dimer in both the unadjusted (r = 0.523, P = 0.038) and a model adjusted for contemporaneous aortic root diameter (r = 0.733, P = 0.028). Our study revealed that overnight CPAP reduces D-dimer levels commensurate with the elimination of OSA and concomitant hemodynamic fluctuations. Morning D-dimer measurements together with OSA screening might serve as predictors of vascular injury in MFS.NEW & NOTEWORTHY What is New? Surges in blood pressure caused by obstructive sleep apnea during sleep increase vascular stress and D-dimer levels in Marfan syndrome. Elevations in D-dimer can be lowered with CPAP. What is Noteworthy? D-dimer levels might serve as a marker for determining the significance of obstructive sleep apnea in persons with Marfan syndrome. D-dimer or obstructive sleep apnea screening is a potential method to identify persons with Marfan syndrome at risk for adverse cardiovascular events.

Assessment of pleural pressure during sleep in Marfan syndrome.

STUDY OBJECTIVES: Patients with Marfan syndrome (MFS) have a high risk for aortic aneurysms. They are also susceptible to sleep-disordered breathing that may expose them to highly negative intrathoracic pressures known to increase aortic transmural pressure, which may accelerate aortic dilatation. Our objective was to quantify overnight intrathoracic pressure changes during sleep in snoring patients with MFS and the therapeutic effect of continuous positive airway pressure (CPAP). METHODS: We used a questionnaire to identify self-reported snoring patients with MFS. In these patients, we monitored intrathoracic pressure using esophageal pressure (Pes) during overnight baseline and CPAP sleep studies. We defined a peak-inspiratory Pes (Pespeak-insp) < - 5 cm H2O as greater than normal and examined the distribution of Pespeak-insp during baseline and CPAP studies. RESULTS: In our sample of 23 snorers with MFS, we found that 70% of sleep breaths exhibited Pespeak-insp < -5 cm H2O, with apnea/hypopneass accounting for only 12%, suggesting prevalent stable flow-limited breathing and snoring. In a subset (n = 12) with Pes monitoring during a CPAP night, CPAP lowered the mean proportion of breaths with Pespeak-insp < -5 cm H2O from 83.7% ± 14.9% to 3.6% ± 3.0% (P < .001). In addition, contemporaneous aortic root diameter was associated with the mean Pespeak-insp during inspiratory flow-limited breathing and apneas/hypopneas (ß = -0.05, r = .675, P = .033). CONCLUSIONS: The sleep state in MFS revealed prolonged exposure to exaggerated negative inspiratory Pes, which was reversible with CPAP. Since negative intrathoracic pressure can contribute to thoracic aortic stress and aortic dilatation, snoring may be a reversible risk factor for progression of aortic pathology in MFS. CITATION: Sowho M, Jun J, Sgambati F, et al. Assessment of pleural pressure during sleep in Marfan syndrome. J Clin Sleep Med. 2022;18(6):1583-1592.

Fetal neuromaturation in late gestation is affected by maternal sleep disordered breathing and sleep disruption in pregnant women with obesity.

OBJECTIVE: Maternal sleep disordered breathing and sleep disruption have adverse effects on pregnancy outcomes through multiple potential pathophysiologic pathways. We hypothesize that disordered maternal sleep also adversely impacts the neuromaturation of the fetus. METHODS: Participants in this prospective observational study included 102 obese pregnant women (pre-pregnancy body mass index [BMI] of 30 or higher) at 36 weeks of pregnancy. Fetal neuromaturation, defined through measures of fetal heart rate variability, motor activity, and motor-cardiac coupling, was quantified through digitized fetal actocardiography during an afternoon recording. Maternal sleep measures were collected overnight through polysomnography. Data analysis focused on multiple regression, controlling for maternal BMI, blood pressure, and diabetes. RESULTS: Indicators of higher sleep disordered breathing were associated with delayed fetal neuromaturation and greater fetal motor activity. Less maternal sleep disruption (shorter rapid eye movement [REM] latency, more REM sleep, and/or fewer transitions) was associated with higher fetal heart rate variability and coupling-based neuromaturation. CONCLUSION: Characteristics of disordered maternal sleep affect the developing fetal nervous system. It is unknown whether these results extend to populations that are not characterized by obesity. The influence of maternal sleep on the developing fetal nervous system has been understudied and may yield effects that persist beyond pregnancy.

Fetal heart rate during maternal sleep.

Despite prolonged and cumulative exposure during gestation, little is known about the fetal response to maternal sleep. Eighty-four pregnant women with obesity (based on pre-pregnancy BMI) participated in laboratory-based polysomnography (PSG) with continuous fetal electrocardiogram monitoring at 36 weeks gestation. Multilevel modeling revealed both correspondence and lack of it in maternal and fetal heart rate patterns. Fetal heart rate (fHR) and variability (fHRV), and maternal heart rate (mHR) and variability (mHRV), all declined during the night, with steeper rates of decline prior to 01:00. fHR declined upon maternal sleep onset but was not otherwise associated with maternal sleep stage; fHRV differed during maternal REM and NREM. There was frequent maternal waking after sleep onset (WASO) and fHRV and mHRV were elevated during these episodes. Cross-correlation analyses revealed little temporal coupling between maternal and fetal heart rate, except during WASO, suggesting that any observed associations in maternal and fetal heart rates during sleep are the result of other physiological processes. Implications of the maternal sleep context for the developing fetus are discussed, including the potential consequences of the typical sleep fragmentation that accompanies pregnancy.

Acute Altitude Acclimatization in Young Healthy Volunteers: Nocturnal Oxygenation Increases Over Time, Whereas Periodic Breathing Persists.

Ju, Jia-Der, Cristian Zhang, Francis P. Sgambati, Lidia M. Lopez, Luu V. Pham, Alan R. Schwartz, and Roberto A. Accinelli. Acute altitude acclimatization in young healthy volunteers: nocturnal oxygenation increases over time whereas periodic breathing persists. High Alt Med Biol. 22:14-23, 2021. Study Objectives: This study aimed to examine the acute effects of high altitude (HA) on sleep disordered breathing (sleep apnea and nocturnal hypoxemia) and acute mountain sickness and to characterize acclimatization over time. Methods: Ten native lowlanders residing at sea level (SL) completed the Lake Louise Score (LLS) and underwent nocturnal polygraphy (ApneaLink Plus) for nine consecutive nights (N1-N9) at HA (2,761 m) and two nights before and after HA. Nocturnal oxygen profiles were assessed by measuring the mean nocturnal oxyhemoglobin saturation (SpO2) during sleep, and sleep apnea severity as assessed by measuring the Apnea-Hypopnea Index (AHI). Mixed-effects linear regression was used to model responses in outcomes (mean nocturnal SpO2, logAHI, and LLS) between HA and SL. Changes in SpO2 and AHI were examined in subgroups with mild versus marked nocturnal SpO2 and low versus high AHI during exposure to HA and compared between subgroups. Results: Compared with SL, the mean nocturnal SpO2 was lower (p < 0.0001) and AHI was higher (p < 0.0001) at HA. The mean nocturnal SpO2 increased progressively (p < 0.001), whereas AHI remained high (p < 0.978) and relatively unchanged over nine successive nights at HA. Those with markedly reduced SpO2 upon arrival at HA exhibited progressive increases in the mean nocturnal SpO2 over time at HA compared with those with mild nocturnal desaturation. LLS rose at HA, but no differences were observed between subgroups. Conclusions: In healthy HA sojourners, the mean nocturnal SpO2 increased progressively over time, whereas AHI remained elevated, suggesting distinctive phenotypes and acclimatization responses to HA.

Brief digital sleep questionnaire powered by machine learning prediction models identifies common sleep disorders.

INTRODUCTION: We developed and validated an abbreviated Digital Sleep Questionnaire (DSQ) to identify common societal sleep disturbances including insomnia, delayed sleep phase syndrome (DSPS), insufficient sleep syndrome (ISS), and risk for obstructive sleep apnea (OSA). METHODS: The DSQ was administered to 3799 community volunteers, of which 2113 were eligible and consented to the study. Of those, 247 were interviewed by expert sleep physicians, who diagnosed ≤2 sleep disorders. Machine Learning (ML) trained and validated separate models for each diagnosis. Regularized linear models generated 15-200 features to optimize diagnostic prediction. Models were trained with five-fold cross-validation (repeated five times), followed by robust validation testing. ElasticNet models were used to classify true positives and negatives; bootstrapping optimized probability thresholds to generate sensitivities, specificities, accuracies, and area under the receiver operating curve (AUC). RESULTS: Compared to reference subgroups, physician-diagnosed sleep disorders were marked by DSQ evidence of sleeplessness (insomnia, DSPS, OSA), sleep debt (DSPS, ISS), airway obstruction during sleep (OSA), blunted circadian variability in alertness (DSPS), sleepiness (DSPS and ISS), increased alertness (insomnia) and global impairment in sleep-related quality of life (all sleep disorders). ElasticNet models validated each diagnosis with high sensitivity (80-83%), acceptable specificity (63-69%), high AUC (0.80-0.85) and good accuracy (agreement with physician diagnoses, 68-73%). DISCUSSION: A brief DSQ readily engaged and efficiently screened a large population for common sleep disorders. Powered by ML, the DSQ can accurately classify sleep disturbances, demonstrating the potential for improving the sleep, health, productivity and safety of populations.

Novel phrenic nerve stimulator treats Cheyne-Stokes respiration: polysomnographic insights.

None: A symptomatic patient with atrial fibrillation and Cheyne-Stokes respiration (CSR) was implanted with a transvenous phrenic nerve stimulation (TPNS) device-the remede System-that is indicated for adult patients with moderate to severe central sleep apnea. Sleep recordings demonstrated that TPNS eliminated periodic breathing by activating the diaphragm and stabilizing respiratory patterns. These recordings of preprogrammed periods on versus off TPNS illustrate prompt (1) stabilization of tidal airflow, respiratory effort, and oxygenation as stimulation amplitude increased stepwise and (2) recurrence of CSR immediately after TPNS deactivated. Despite differences in respiratory patterns, minute ventilation was comparable during periods on and off TPNS. These findings suggest that diaphragmatic pacing entrains ventilation without disrupting sleep, accounting for observed improvements in periodic breathing, gas exchange, sleep architecture, and quality of life. Effective means to relieve CSR could potentially mitigate nocturnal cardiovascular stress and disease progression.

Snoring: a source of noise pollution and sleep apnea predictor.

Snoring is a highly prevalent condition associated with obstructive sleep apnea (OSA) and sleep disturbance in bed partners. Objective measurements of snoring in the community, however, are limited. The present study was designed to measure sound levels produced by self-reported habitual snorers in a single night. Snorers were excluded if they reported nocturnal gasping or had severe obesity (BMI > 35 kg/m2). Sound was measured by a monitor mounted 65 cm over the head of the bed on an overnight sleep study. Snoring was defined as sound ≥40 dB(A) during flow limited inspirations. The apnea hypopnea index (AHI) and breath-by-breath peak decibel levels were measured. Snore breaths were tallied to determine the frequency and intensity of snoring. Regression models were used to determine the relationship between objective measures of snoring and OSA (AHI ≥ 5 events/h). The area under the curve (AUC) for the receiver operating characteristic (ROC) was used to predict OSA. Snoring intensity exceeded 45 dB(A) in 66% of the 162 participants studied, with 14% surpassing the 53 dB(A) threshold for noise pollution. Snoring intensity and frequency were independent predictors of OSA. AUCs for snoring intensity and frequency were 77% and 81%, respectively, and increased to 87% and 89%, respectively, with the addition of age and sex as predictors. Snoring represents a source of noise pollution in the bedroom and constitutes an important target for mitigating sound and its adverse effects on bed partners. Precise breath-by-breath identification and quantification of snoring also offers a way to risk stratify otherwise healthy snorers for OSA.

The Efficacy of Low-Level Continuous Positive Airway Pressure for the Treatment of Snoring.

STUDY OBJECTIVES: To assess effects of low-level continuous positive airway pressure (CPAP) on snoring in habitual snorers without obstructive sleep apnea (OSA). METHODS: A multicenter prospective in-laboratory reversal crossover intervention trial was conducted between September 2013 and August 2014. Habitual snorers were included if they snored (inspiratory sound pressure level ≥ 40 dBA) for ≥ 30% all sleep breaths on a baseline sleep study (Night 1), and if significant OSA and daytime somnolence were absent. Included participants then underwent a CPAP titration study at 2, 4, or 6 cm H2O (Night 2) to examine snoring responses to step-increases in nasal pressure, a treatment night at optimal pressure (Night 3), followed by baseline night (Night 4). At each pressure, snoring intensity was measured on each breath. Snoring frequency was quantified as a percentage of sleep breaths at thresholds of 40, 45, 50, and 55 dBA. Sleep architecture and OSA severity were characterized using standard measurements. RESULTS: On baseline sleep studies, participants demonstrated snoring at ≥ 40 dBA on 53 ± 3% and ≥ 45 dBA on 35 ± 4% of breaths. Snoring frequency decreased progressively as nasal pressure increased from 0 to 4 cm H2O at each threshold, and plateaued thereafter. CPAP decreased snoring frequency by 67% and 85% at 40 and 45 dBA, respectively. Intervention did not alter sleep architecture and sleep apnea decreased minimally. CONCLUSIONS: Low-level CPAP below the range required to treat OSA diminished nocturnal snoring, and produced uniform reduction in nightly noise production below the World Health Organization's limit of 45 dBA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT01949584.

MATPLM1, A MATLAB script for scoring of periodic limb movements: preliminary validation with visual scoring.

BACKGROUND AND PURPOSE: A Matrix Laboratory (MATLAB) script (MATPLM1) was developed to rigorously apply World Associations of Sleep Medicine (WASM) scoring criteria for periodic limb movements in sleep (PLMS) from bilateral electromyographic (EMG) leg recordings. This study compares MATPLM1 with both standard technician and expert detailed visual PLMS scoring. METHODS AND SUBJECTS: Validation was based on a 'macro' level by agreement for PLMS/h during a night recording and on a 'micro' level by agreement for the detection of each PLMS from a stratified random sample for each subject. Data available for these analyses were from 15 restless leg syndrome (RLS) (age: 61.5 ± 8.5, 60% female) and nine control subjects (age: 61.4 ± 7.1, 67% female) participating in another study. RESULTS: In the 'micro' analysis, MATPLM1 and the visual detection of PLMS events agreed 87.7% for technician scoring and 94.4% for expert scoring. The technician and MATPLM1 scoring disagreements were checked for 36 randomly selected events, 97% involved clear technician-scoring error. In the 'macro' analysis, MATPLM1 rates of PMLS/h correlated highly with visual scoring by the technician (r(2) = 0.97) and the expert scorer (r(2) = 0.99), but the technician scoring was consistently less than MATPLM1: median (quartiles) difference: 10 (5, 23). There was little disagreement with expert scorer [median (quartile) difference: -0.3 (-2.4, 0.3)]. CONCLUSIONS: The MATPLM1 produces reliable scoring of PLMS that matches expert scoring. The standard visual scoring without careful measuring of events tends to significantly underscore PLMS. These preliminary results support the use of MATPLM1 as a preferred method of scoring PLMS for EMG recordings that are of a good quality and without significant sleep-disordered breathing events.

Altered pain responses in abstinent (±)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") users.

RATIONALE: (±)3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that has potential to damage brain serotonin (5-HT) neurons in humans. Brain 5-HT neurons play a role in pain modulation, yet little is known about long-term effects of MDMA on pain function. Notably, MDMA users have been shown to have altered sleep, a phenomenon that can lead to altered pain modulation. OBJECTIVES: This study sought to assess pain processing in MDMA users using objective methods, and explore potential relationships between pain processing and sleep indices. METHODS: Forty-two abstinent MDMA users and 43 age-matched controls participated in a 5-day inpatient study. Outcome measures included standardized measures of pain, sleep polysomnograms, and power spectral measures of the sleep EEG. When differences in psychophysiological measures of pain were found, the relationship between pain and sleep measures was explored. RESULTS: MDMA users demonstrated lower pressure pain thresholds, increased cold pain ratings, increased pain ratings during testing of diffuse noxious inhibitory control, and decreased Stage 2 sleep. Numerous significant relationships between sleep and pain measures were identified, but differences in sleep between the two groups were not found to mediate altered pain perception in MDMA users. CONCLUSIONS: Abstinent MDMA users have altered pain perception and sleep architecture. Although pain and sleep outcomes were related, differences in sleep architecture in MDMA users did not mediate altered pain responses. It remains to be determined whether alterations in pain perception in MDMA users are secondary to neurotoxicity of 5-HT-mediated pain pathways or alterations in other brain processes that modulate pain perception.

Sleep apnea in young abstinent recreational MDMA ("ecstasy") consumers.

BACKGROUND: Methylenedioxymethamphetamine (MDMA, "ecstasy") is a popular recreational drug of abuse and a selective brain serotonin neurotoxin. Functional consequences of MDMA neurotoxicity have defied ready characterization. Obstructive sleep apnea (OSA) is a common form of sleep-disordered breathing in which brain serotonin dysfunction may play a role. The present study sought to determine whether abstinent recreational MDMA users have an increased prevalence of OSA. METHODS: We studied 71 medically healthy recreational MDMA users and 62 control subjects using all-night sleep polysomnography in a controlled inpatient research setting. Rates of apneas, hypopneas, and apnea hypopnea indices were compared in the 2 groups, controlling for body mass index, age, race, and gender. RESULTS: Recreational MDMA users who had been drug free for at least 2 weeks had significantly increased rates of obstructive sleep apnea and hypopnea compared with controls. The odds ratio (95% confidence interval) for sleep apnea (mild, moderate, and severe combined) in MDMA users during non-REM sleep was 8.5 (2.4-30.4), which was greater than that associated with obesity [6.9 (1.7-28.2)]. Severity of OSA was significantly related to lifetime MDMA exposure. CONCLUSIONS: These findings suggest that prior recreational methylenedioxymethamphetamine use increases the risk for obstructive sleep apnea and lend support to the notion that brain serotonin neuronal dysfunction plays a role in the pathophysiology of sleep apnea.

Sleep deprivation differentially impairs cognitive performance in abstinent methylenedioxymethamphetamine ("Ecstasy") users.

Methylenedioxymethamphetamine (MDMA; "Ecstasy") is a popular recreational drug and brain serotonin (5-HT) neurotoxin. Neuroimaging data indicate that some human MDMA users develop persistent deficits in brain 5-HT neuronal markers. Although the consequences of MDMA-induced 5-HT neurotoxicity are not fully understood, abstinent MDMA users have been found to have subtle cognitive deficits and altered sleep architecture. The present study sought to test the hypothesis that sleep disturbance plays a role in cognitive deficits in MDMA users. Nineteen abstinent MDMA users and 21 control subjects participated in a 5 d inpatient study in a clinical research unit. Baseline sleep quality was measured using the Pittsburgh Sleep Quality Inventory. Cognitive performance was tested three times daily using a computerized cognitive battery. On the third day of admission, subjects began a 40 h sleep deprivation period and continued cognitive testing using the same daily schedule. At baseline, MDMA users performed less accurately than controls on a task of working memory and more impulsively on four of the seven computerized tests. During sleep deprivation, MDMA users, but not controls, became increasingly impulsive, performing more rapidly at the expense of accuracy on tasks of working and short-term memory. Tests of mediation implicated baseline sleep disturbance in the cognitive decline seen during sleep deprivation. These findings are the first to demonstrate that memory problems in MDMA users may be related, at least in part, to sleep disturbance and suggest that cognitive deficits in MDMA users may become more prominent in situations associated with sleep deprivation.