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Biomedical subjects

Stephen P Duntley

Publications and source records attributed to Stephen P Duntley.

9 recordsLinked to original sources

Identification of a biomarker for sleep drive in flies and humans.

It is a common experience to sacrifice sleep to meet the demands of our 24-h society. Current estimates reveal that as a society, we sleep on average 2 h less than we did 40 years ago. This level of sleep restriction results in negative health outcomes and is sufficient to produce cognitive deficits and reduced attention and is associated with increased risk for traffic and occupational accidents. Unfortunately, there is no simple quantifiable marker that can detect an individual who is excessively sleepy before adverse outcomes become evident. To address this issue, we have developed a simple and effective strategy for identifying biomarkers of sleepiness by using genetic and pharmacological tools that dissociate sleep drive from wake time in the model organism Drosophila melanogaster. These studies have identified a biomarker, Amylase, that is highly correlated with sleep drive. More importantly, both salivary Amylase activity and mRNA levels are also responsive to extended waking in humans. These data indicate that the fly is relevant for human sleep research and represents a first step in developing an effective method for detecting sleepiness in vulnerable populations.

Amylases↗

Circadian and ultradian rhythms in heart rate variability.

AIM: Heart rate variability (HRV) patterns reflect the changing effect of sympathetic and parasympathetic modulation of the autonomic nervous system. While overall and circadian heart rate (HR) and HRV are well characterized by traditional measures, there is currently no method to measure ultradian cycles of HR and HRV. MATERIALS AND METHODS: HR/HRV for each 2-min interval was calculated using normal-to-normal interbeat intervals from overnight polysomnographic ECGs in 113 subjects, aged 58+/-10 years (65 male, 48 female). HR, SDNN2, high-frequency power (HF) and the LF (low-frequency power)/HF ratio were plotted. A curve-fitting algorithm, developed in MatLab, identified cyclic patterns of HR/HRV and extracted parameters to characterize them. Results were compared for older vs. younger patients, males vs. females, with vs. without severe sleep apnea, and for the upper and lower half of sleep efficiency. RESULTS: Ultradian patterns for different HR/HRV indices had variable correspondences with each other and none could be considered surrogates. Differences were seen for all comparison groups, but no one marker was consistently different across comparisons. CONCLUSION: Each HR/HRV parameter has its own rhythm, and the correspondence between these rhythms varies greatly across subjects. Quantification of ultradian patterns of HRV is feasible and could provide new insights into autonomic physiology.

Age Factors↗

An evaluation of the use of seizure prone rats when investigating intermediate stage sleep.

A body of literature is developing which identifies an additional stage of sleep in rats, cats and mice. Intermediate stage (IS) sleep is a measurable sleep stage that is maintained by the hyperpolarization of GABA(A) containing thalamocortical neurons. The present study attempts to clarify inconsistencies within the sleep spindle literature. Most notably, inconsistencies between those that study sleep spindles in the rat outside and within the context of IS sleep. Ten male taiep rats weighing from 400 g to 600 g, and 9-12 months of age, were used in this study. The animals were given a one-time, .9 mg/kg dose of the benzodiazepine clonazepam. The control group had more seizure activity (mean = 13.4) than the treatment group (mean = 5.2, t(1-18) = 8.859, p < .001), and had a lower number of sleep spindles (mean=10.3) than the treatment group (mean = 13.3, t(1-18) = -3.4, p < .001). In addition, spectral analysis of sleep spindles during IS and seizure activity revealed that sleep spindles are within the frequency band of 8-11Hz, while seizure activity is within the 4-7 Hz range. This data supports the hypotheses that sleep spindles are distinguishable from seizure activity.

Animals↗

The relationship of sleep disturbances and fatigue in multiple sclerosis.

BACKGROUND: Fatigue is experienced by most patients with multiple sclerosis (MS) and often is profoundly debilitating. No large-scale studies to our knowledge have examined circadian rhythm abnormalities in MS patients or the relationship of fatigue to circadian rhythms. OBJECTIVE: To determine if patients with MS and fatigue have sleep disturbances or circadian rhythm abnormalities associated with fatigue. DESIGN: Case-control study. SETTING: Washington University School of Medicine, St Louis, Mo. PATIENTS: Fifteen patients with MS and fatigue were compared with 15 patients with MS without fatigue and 15 age- and sex-matched, healthy controls. MAIN OUTCOME MEASURES: Sleep disturbances and circadian rhythm abnormalities were quantitated by actigraphy, fatigue by the Fatigue Descriptive Scale, and excessive sleepiness by the Epworth Sleepiness scale (ESS). RESULTS: Of the 15 fatigued patients with MS, 2 had delayed sleep phase, 10 had disrupted sleep, and 3 had normal sleep. One of the 15 nonfatigued MS patients had irregular sleep cycles, 2 others had disrupted sleep, and 12 had normal sleep. All 15 of the healthy controls had normal sleep. Nine patients with MS and fatigue scored 10 or higher on the ESS, suggesting excessive daytime sleepiness. Only 2 patients with MS without fatigue scored higher than 10 on the ESS. None of the healthy controls were fatigued, and 14 were not excessively sleepy. A relationship was found between fatigue and abnormal sleep cycles or disrupted sleep (Fisher exact test, P =.003). There was also a relationship between subjective excessive daytime sleepiness and fatigue in MS patients (P =.02). CONCLUSION: There is a significant correlation between fatigue in MS patients and disrupted sleep or abnormal sleep cycles.

Adult↗

Effect of cognitive behavioral therapy on heart rate variability during REM sleep in female rape victims with PTSD.

Six female rape victims with posttraumatic stress disorder (PTSD) were assessed for sleep disturbances. Five responded to cognitive-behavioral therapy (CBT) and one did not complete treatment. Sympatho-vagal balance was measured using heart rate variability (HRV) during rapid eye movement (REM) sleep. The treatment responders significantly decreased on HRV while the noncompleter increased. The responders also significantly decreased on sleep disturbances. The noncompleter remained unchanged. Thus a remission in PTSD symptoms following CBT accompanied a reduction in the HRV indicator of sympathetic predominance in REM sleep.

Adult↗

A simple method to identify sleep apnea using Holter recordings.

INTRODUCTION: Despite its severe cardiovascular and other consequences, sleep apnea syndrome frequently is undiagnosed. Because apneas result in repeated autonomic arousals associated with cyclic variations in heart rate (CVHR), we hypothesized that sleep apnea syndrome could be identified from simple HR tachograms (graphs of HR vs time) derived from ECG monitoring. METHODS AND RESULTS: HR tachograms were generated from 57 digitized ECGs (46 clinical patients undergoing diagnostic studies and 11 research subjects) obtained during overnight polysomnography. Thirty-three had significant sleep apnea syndrome (apnea-hypopnea index > or = 15). Eight patients had simultaneous Holter recordings during sleep studies (3 with digitized ECGs and 5 with paper ECGs). Duration of CVHR on tachograms was determined. CVHR patterns were characterized as high amplitude (HR changes > or = 20 beats/min per cycle) versus lower amplitude (6-19 beats/min per cycle); or regular (in frequency, amplitude, and morphology) versus irregular. Tachograms were classified as having visible HR changes versus not visible (flat). Twenty-four studies proved to be split-night, so CVHR was quantified for the first 3 hours of each study only. When subjects were dichotomized into shorter (< 20%, < 36 min) and longer (> or = 20%) durations of CVHR, longer CVHR had a positive predictive accuracy of 86% for significant sleep apnea syndrome and 100% for abnormal sleep. When flat tachograms were excluded, negative predictive accuracy for shorter CVHR was 100%. All patients (N = 13) with > 36 min high-amplitude CVHR had significant obstructive sleep apnea. All predictions from Holter-only data were concordant with clinical diagnoses. CONCLUSION: HR tachogram patterns derived from ambulatory ECGs provide a simple method for identifying sleep apnea syndrome and other sleep disturbances in patients without major autonomic dysfunction.

Adult↗

Learning, memory, and executive control in individuals with obstructive sleep apnea syndrome.

A range of neuropsychological deficits have been identified in individuals with obstructive sleep apnea syndrome (OSAS) and have been related to disruptions in function of the frontal cortex of the brain. We hypothesized that impairments in the use of strategic, frontally-mediated processes that facilitate learning and memory would be associated with deficits in the long-term episodic memory of verbal material (i.e., word lists). We evaluated 28 adults with OSAS and 24 controls (ranging from 28 to 60 years of age) using the California Verbal Learning Test. General executive abilities were assessed using the Wisconsin Card Sorting Test, Letter fluency, and Category fluency. Individuals with OSAS exhibited poorer recall across learning trials, less efficient use of semantic clustering, and poorer use of semantic cues. Retention of previously encoded information and recognition, however, were intact. With the exception of letter fluency, deficits were not observed in general executive control. Results are discussed within the context of disruptions in the interactions between long-term memory and executive abilities that are subserved by frontal and distal brain regions.

Adult↗

Depression predicts self-reported sleep quality in patients with obstructive sleep apnea.

OBJECTIVE: Depression is a common problem in patients with obstructive sleep apnea. The objective of this study was to examine whether depression is independently associated with lower self-reported sleep quality in patients with obstructive sleep apnea (OSA), after controlling for polysomnographic measures of sleep. METHODS: The sample comprised 135 patients who had been referred to a university teaching hospital's multidisciplinary sleep medicine center for polysomnographic evaluation of OSA. The median age of the subjects was 45 (mean age, 46 years) 55% were female, 69% were white, 31% were black, and their mean body mass index was 37.9 +/- 11.2 kg/m2. Self-reported sleep quality during the past 2 weeks was assessed by the insomnia severity index. Polygraphic measures of sleep quality included the respiratory disturbance index, sleep onset latency, arousals for no apparent reason, sleep efficiency, and periodic leg movements associated with arousal. Depressive symptoms were assessed by the Beck Depression Inventory. RESULTS: None of the polygraphic measures of sleep quality was related to self-reported sleep quality or depression. Oxygen desaturation was correlated with self-reported sleep quality (r = 0.21, p =.02). Depression correlated with self-reported sleep quality (r = 0.55, p <.0001). In a multiple regression analysis, depression remained a significant predictor of self-reported sleep quality after controlling for all of the polysomnographic measures of sleep quality (F = 9.65, partial r2 = 0.28 p =.0001). CONCLUSION: Depression is a better predictor of self-reported sleep quality than are polysomnographic measures of sleep in patients with OSA.

Adolescent↗

Depression and obstructive sleep apnea in patients with coronary heart disease.

OBJECTIVE: Depression is a risk factor for cardiac events in patients with coronary heart disease (CHD). Obstructive sleep apnea/hypopnea syndrome (OSAHS) is frequently comorbid with depression and is also a risk factor for cardiac events. Undetected OSAHS could help explain the increased risk associated with depression. METHODS: Medically stable patients with CHD and major (MD, n = 53), minor (md, n = 36), or no depression (ND, n = 43) were evaluated for 2 nights in a sleep medicine laboratory. RESULTS: The prevalence of OSAHS did not differ across groups (MD 66%, md 69%, ND 77%; p > .05). Patients with MD had a significantly greater frequency of apneic episodes, a significantly longer duration of apneas and hyponeas, and more oxygen desaturations per hour than those with md, but there were no differences between MD and ND in frequency of apneic episodes or oxygen desaturations. However, males with MD tended to have more obstructive episodes per hour than did ND males, whereas females with MD had fewer episodes than did ND females. Apnea duration was longer in patients with MD compared with patients with no ND. There was no difference in the mean duration of apnea per hour between the md and ND groups. CONCLUSIONS: Although OSAHS is not more common in depressed patients with CHD, MD is associated with longer obstructive sleep apneic episodes in both men and women and with a higher frequency of episodes in men.

Adult↗