Bioinformatics

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

Project 1: Age Trajectories of O2 Saturation and Levels of Serum Bicarbonate or End-Tidal CO2 Across the Life Course for Women and Men: Insights from EHR and PSG Data To elucidate changes in gas exchange across the life course, we estimated age trajectories of O2 saturation, CO2 (as either end-tidal or serum bicarbonate), resting heart rate, and resting respiratory rate from age 2 yr onward in female and male patients separately. We utilized two sources’ data: electronic health records (EHR) representing ambulatory visits of approximately 53,000 individuals and sleep-clinic polysomnogram (PSG) records representing an additional ~21,000. We used linear regression to estimate age-group-specific mean response levels for women and men. We compared estimated female-male differences between pre- and post-pubertal children and between pre- and post-menopausal periods among adults. Women between 15-45 yrs had higher O2 saturation and lower serum bicarbonate levels or end-tidal CO2 levels than men of similar ages. For O2 saturation and for both measures of CO2, the female-male difference was larger on average among adults at pre-menopausal ages than those at post-menopausal ages. Women had higher O2 saturation throughout their lives than men; however, the difference disappeared in the elderly. Women between menarche and menopause had significantly lower end-tidal CO2 and serum bicarbonate than men of similar ages. After menopause, however, women appeared to have higher mean levels of both end-tidal CO2 and serum bicarbonate than men. Project 2: Comparison of overnight trends in relative power for specific frequency bands, sleep stages, and brain regions between patients with depressive disorder and matched control subjects Major depressive disorder (MDD) is one of the most prevalent and debilitating mental illnesses worldwide. MDD is characterized by depressed mood, lack of interests, impaired cognitive function accompanied by physical changes such as weight gain or less loss (American Psychiatric Association, 2022). Patients with MDD experience loss of interest or pleasure in daily activity and often have problems with sleep, eating, concentration, energy, and self-worth. MDD affects hundreds of millions of people world-wide. According to the National Institute of Mental Health (NIMH), in the United States alone, in 2021, an estimated 21.0 million adults (8.3% of adults) had at least one major depressive episode. The etiology of MDD is multifactorial and has both genetic and environmental components. MDD affects twice as many women as men. Few EEG studies on MDD have been carried out during sleep. Most EEG studies of MDD used routine EEG in which subjects are either at rest, with eyes open or closed, or performing a task. Such studies typically involved a short recording time ranging from minutes to an hour. Results from those studies suggest that the theta oscillations (4-7 Hz) are altered in MDD patients compared to healthy controls. In contrast, overnight PSG studies include several hours of EEG recording, making it possible to study temporal changes in EEG power during sleep. The few existing sleep EEG studies of MDD primarily focused on temporal trends in slow-wave EEG power using an exponential relationship that had been proposed earlier. The authors showed that the ratio of slow-wave activity in the first non-REM (NREM) period relative to the second NREM period (referred to as dissipation) was lower in patients with MDD than non-patients. These authors did not obtain patient-specific estimates of trend but, instead, provided an overall regression estimate by synchronizing the sleep data to the same number of NREM periods or hours of sleep. Moreover, little is known about temporal trends for other EEG frequency bands in MDD patients during sleep. Most EEG studies of MDD examined mean differences in frequency-band-specific power between MDD patients and control subjects; however, a few studies looked for differences in temporal trends in power. We focused on overnight time trends in relative power using polysomnography studies of 544 patients with MDD and 1,662 age- and sex-matched controls. We sought to replicate our finding on MDD with an additional 653 patients with depressive disorder (DD) and 1,959 age- and sex-matched controls. For each subject, we estimated trends as regression slopes separately for 180 features defined by six frequency bands, five sleep stages, and six brain regions. Relative theta power during stage 2 (N2) non-rapid eye movement (NREM) sleep in the frontal and central regions of the brain increased more rapidly through time in MDD patients than in controls. Similar upward trends of relative theta power were also statistically significant in DD patients. If validated in a longitudinal study, the time trend in relative theta power in the N2 stage of the NREM sleep could potentially serve as a surrogate biomarker for monitoring the responses of patients with depressive disorders to treatment. Project 3: Sex- and Age-differences in Supine Positional Obstructive Sleep Apneas in Children and Adults Sleep apnea is a common sleep disorder and is characterized by abnormalities of respiration during sleep. Sleep apnea causes normal breathing to stop or get very shallow. Apnea is a complete cessation of airflow that lasts at least 10 seconds and hypopnea is defined as decrease in airflow of at least 30% and a decrease in oxygen saturation of at least 3% or an arousal, both of which last at least 10 seconds. Obstructive sleep apnea (OSA), the most common form of sleep apnea, happens when the upper airway becomes blocked during sleep, thereby reducing or completely stopping airflow. The occurrence of OSA can depend on sleep position. The American Academy of Sleep Medicine (AASM) defines positional OSA as a lower apnea/hypopnea index (AHI) in the non-supine position than in the supine position. In practice, supine positional OSA is usually defined when, among those with OSA, AHI during sleep in the supine position is at least twice as high as AHI in other positions. Positional OSA (POSA) is thought to be caused by unfavorable airway geometry, reduced lung volume, inability of airway dilator muscles to adequately compensate air loss in the supine position. POSA is prevalent. In a cohort study of 574 OSA patients, 56% were found to have POSA. A similar proportion (54%) was found in 6,437 OSA patients. Moreover, about 20% of the adult OSA patients had exclusive supine positional OSA (e-POSA) (ratio of supine AHI to non-supine AHI ≥ 2 and non-supine AHI < 5). It was found that POSA was present in 53% of the general population and in 75% of OSA subjects and that the prevalence of e-POSA among OSA subjects was 36%. We carried out retrospective analysis of polysomnography studies from 13,144 individuals aged from 2 to 103 years old with at least 30 min of both supine and lateral sleep. We used generalized linear mixed-effects models to estimate position-specific mean apnea-hypopnea index (AHI) values and logistic regression to estimate the proportion with POSA or with exclusive POSA among individuals with OSA. Predictors included sex, 5-y age group, sleep position, and their interactions. We found that supine AHI was higher than lateral AHI regardless of age or sex except under age 5 y. The ratio of supine AHI to lateral AHI reliably exceeded 2 after age 30-35 in males and age 50-55 in females. For both sexes, the proportion with POSA among individuals with OSA increased rapidly with age until 30-35 and then stabilized. The proportion with POSA among individuals with OSA was significantly higher in males than females for each age group between 40 and 75 (p < 0.03). Among individuals with OSA in those 20 and older, the proportion with POSA was 64.6% (95% CI: 62.7%, 66.5%) in males and 55.8% (95% CI: 53.6%, 57.8%) in females. The proportion of individuals showing exclusive POSA also increased with age and peaked near 41% at age 15-20 in males and at age 20-25 in females. In conclusion, POSA becomes more common with age in both sexes; in women, its prevalence is generally lower but continues to increase after age 65.