Richard T. Loving

Laboratory assessment of diurnal and nocturnal ocular perfusion pressures in humans

We estimated diurnal and nocturnal levels of ocular perfusion pressure at rest in both young and older adults in a clinical sleep laboratory. Measurements of blood pressure and intraocular pressure (IOP) were obtained every 2 hours for 24 consecutive hours in 16 healthy young adults (ages 18-25 years) and 16 older adults (ages 47-74 years). In the 16-hour diurnal wake period, blood pressure and IOP were measured after a 5-minute sitting rest. In the 8-hour nocturnal period, measurements were taken with subjects in the supine position. Sitting and supine ocular perfusion pressures in the diurnal and nocturnal periods were calculated respectively based upon the blood pressure and IOP. Ocular perfusion pressure was found to be higher in the older group than in the younger group throughout the 24 hours. The peak of ocular perfusion pressure was in the nocturnal period for both groups. Within each subject group, the average nocturnal ocular perfusion pressure in the supine position was higher than the average diurnal ocular perfusion pressure in the sitting position. The diurnal-to-nocturnal increase of ocular perfusion pressure was larger in the older group than in the younger group.

Temperature Circadian Rhythms during the Menstrual Cycle and Sleep Deprivation in Premenstrual Dysphoric Disorder and Normal Comparison Subjects

The aim of this study was to test the hypothesis that the circadian rhythm of core body temperature is altered in premenstrual dysphoric disorder (PMDD) subjects compared to that in normal comparison (NC) subjects and that it is normalized in PMDD subjects after treatment with early night partial sleep deprivation (ESD) or late night partial sleep deprivation (LSD). A total of 23 subjects meeting DSM-IV criteria for PMDD and 18 NC subjects had 24-h core body temperature recordings taken during the following conditions: (1) baseline midfollicular (preovulatory) and (2) late luteal (postovulatory) menstrual cycle phases and after a randomized crossover trial in subsequent luteal phases of (3) ESD, in which subjects slept from 03:00 to 07:00 h, followed by (4) a night of recovery sleep (ESD-R: sleep 22:30 to 06:30 h), and (5) LSD, in which subjects slept from 21:00 to 01:00 h, also followed by (6) a night of recovery sleep (LSD-R: sleep 22:30 to 06:30 h). Temperature amplitudes were significantly decreased in the luteal phase compared to those in the follicular menstrual cycle phase and increased after nights of recovery sleep. Compared to the baseline late luteal phase, during LSD, temperature amplitude increased in PMDD subjects but decreased in NC subjects. During ESD, the temperature acrophase was delayed in PMDD subjects but was advanced in NC subjects; during LSD, the tempera ture acrophase was advanced in PMDD subjects but was delayed in NC subjects compared to the late luteal baseline. Nocturnal temperature and temperature maxima and mesors tended to be higher in PMDD subjects than in NC subjects; when not reduced during sleep deprivation interventions, these were not asso ciated with therapeutic effects. Alterations in both phase and amplitude of temperature circadian rhythms characterize PMDD subjects as contrasted with NC subjects in response to sleep deprivation. The changes in phase reflected more shifts in temperature acrophase in response to shifts in sleep in PMDD subjects. This realignment of the timing of sleep and temperature in addition to the enhancement of blunted amplitude rhythms during recovery nights of sleep may provide corrective mechanisms that contribute to the therapeutic effects of sleep deprivation.

Wrist actigraphic scoring for sleep laboratory patients: algorithm development.

Wrist actigraphy is employed increasingly in sleep research and clinical sleep medicine. Critical evaluation of the performance of new actigraphs and software is needed. Actigraphic sleep–wake estimation was compared with polysomnographic (PSG) scoring as the standard in a clinical sleep laboratory. A convenience sample of 116 patients undergoing clinical sleep recordings volunteered to participate. Actiwatch‐L recordings were obtained from 98 participants, along with 18 recordings using the newer Spectrum model (Philips Electronics), but some of the actigraphic recordings could not be adequately aligned with the simultaneous PSGs. Of satisfactory alignments, 40 Actiwatch recordings were used as a training set to empirically develop a new Scripps Clinic algorithm for sleep–wake scoring. The Scripps Clinic algorithm was then prospectively evaluated in 39 Actiwatch recordings and 16 Spectrum recordings, producing epoch‐by‐epoch sleep–wake agreements of 85–87% and kappa statistics averaging 0.52 (indicating moderate agreement). Wake was underestimated by the scoring algorithm. The correlations of PSG versus actigraphic wake percentage estimates were r = 0.6690 for the Actiwatch and r = 0.2197 for the Spectrum. In general, using a different weighting of activity counts from previous and subsequent epochs, the Scripps Clinic algorithm discriminated sleep–wake more successfully than the manufacturer’s Actiware algorithms. Neither algorithm had fully satisfactory agreement with PSG. Further evaluations of algorithms for these actigraphs are needed, along with controlled comparisons of different actigraphic designs and software.

Bright light treatment of depression for older adults [ISRCTN55452501].

BackgroundThe incidence of insomnia and depression in the elder population is significant. It is hoped that use of light treatment for this group could provide safe, economic, and effective rapid recovery.MethodsIn this home-based trial we treated depressed elderly subjects with bright white (8,500 Lux) and dim red (<10 Lux) light for one hour a day at three different times (morning, mid-wake and evening). A placebo response washout was used for the first week. Wake treatment was conducted prior to the initiation of treatment, to explore antidepressant response and the interaction with light treatment. Urine and saliva samples were collected during a 24-hour period both before and after treatment and assayed for aMT6s and melatonin respectively to observe any change in circadian timing. Subjects wore a wrist monitor to record light exposure and wrist activity. Daily log sheets and weekly mood (GDS) and physical symptom (SAFTEE) scales were administered. Each subject was given a SCID interview and each completed a mood questionnaire (SIGH-SAD-SR) before and after treatment. Also, Hamilton Depression Rating (SIGH-SAD version) interviews were conducted by a researcher who was blind to the treatment condition. A control group of healthy, age-matched, volunteers was studied for one day to obtain baseline data for comparison of actigraphy and hormone levels.ResultsEighty-one volunteers, between 60 and 79 years old, completed the study. Both treatment and placebo groups experienced mood improvement. Average GDS scores improved 5 points, the Hamilton Depression Rating Scale (HDRS) 17 scores (extracted from the self-rated SIGH-SAD-SR) improved 6 points. There were no significant treatment effects or time-by-treatment interactions. No significant adverse reactions were observed in either treatment group. The assays of urine and saliva showed no significant differences between the treatment and placebo groups. The healthy control group was active earlier and slept earlier but received less light than the depressed group at baseline.ConclusionAntidepressant response to bright light treatment in this age group was not statistically superior to placebo. Both treatment and placebo groups experienced a clinically significant overall improvement of 16%.

Efficacy of Enhanced Evening Light for Advanced Sleep Phase Syndrome

This study tested whether a newly designed enhanced evening light therapy was well tolerated and effective in relieving symptoms of Advanced Sleep Phase Syndrome (ASPS). Participants with self-reported ASPS symptoms were 47 older adults (21 men and 26 women, age 60-86). After baseline, participants underwent 28 consecutive days of either dim or enhanced intensity light treatment for 2-3 hr in the evening. Enhanced evening light (~265 lux) exposure was no more effective than a placebo dim light (~2 lux) at alleviating advanced sleep phase as measured by actigraphically recorded sleep and urinary 6-sulphatoxymelatonin (aMT6s) excretion patterns. Participants receiving the enhanced light reported subjective benefit and a significant delay in sleep onset as compared to the placebo. Although compliance was good and the new enhanced evening light therapy design was well tolerated, the benefits were statistically equivocal.

Genetic variants associated with sleep disorders

Objective The diagnostic boundaries of sleep disorders are under considerable debate. The main sleep disorders are partly heritable; therefore, defining heritable pathophysiologic mechanisms could delineate diagnoses and suggest treatment. We collected clinical data and DNA from consenting patients scheduled to undergo clinical polysomnograms, to expand our understanding of the polymorphisms associated with the phenotypes of particular sleep disorders. Methods Patients at least 21 years of age were recruited to contribute research questionnaires, and to provide access to their medical records, saliva for deoxyribonucleic acid (DNA), and polysomnographic data. From these complex data, 38 partly overlapping phenotypes were derived indicating complaints, subjective and objective sleep timing, and polysomnographic disturbances. A custom chip was used to genotype 768 single-nucleotide polymorphisms (SNPs). Additional assays derived ancestry-informative markers (eg, 751 participants of European ancestry). Linear regressions controlling for age, gender, and ancestry were used to assess the associations of each phenotype with each of the SNPs, highlighting those with Bonferroni-corrected significance. Results In peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B), rs6888451 was associated with several markers of obstructive sleep apnea. In aryl hydrocarbon receptor nuclear translocator-like (ARNTL), rs10766071 was associated with decreased polysomnographic sleep duration. The association of rs3923809 in BTBD9 with periodic limb movements in sleep was confirmed. SNPs in casein kinase 1 delta (CSNK1D rs11552085), cryptochrome 1 (CRY1 rs4964515), and retinoic acid receptor-related orphan receptor A (RORA rs11071547) were less persuasively associated with sleep latency and time of falling asleep. Conclusions SNPs associated with several sleep phenotypes were suggested, but due to risks of false discovery, independent replications are needed before the importance of these associations can be assessed, followed by investigation of molecular mechanisms.

Bright green light treatment of depression for older adults [ISRCTN69400161]

BackgroundBright white light has been successfully used for the treatment of depression. There is interest in identifying which spectral colors of light are the most efficient in the treatment of depression. It is theorized that green light could decrease the intensity duration of exposure needed. Late Wake Treatment (LWT), sleep deprivation for the last half of one night, is associated with rapid mood improvement which has been sustained by light treatment. Because spectral responsiveness may differ by age, we examined whether green light would provide efficient antidepressant treatment in an elder age group.MethodsWe contrasted one hour of bright green light (1,200 Lux) and one hour of dim red light placebo (<10 Lux) in a randomized treatment trial with depressed elders. Participants were observed in their homes with mood scales, wrist actigraphy and light monitoring. On the day prior to beginning treatment, the participants self-administered LWT.ResultsThe protocol was completed by 33 subjects who were 59 to 80 years old. Mood improved on average 23% for all subjects, but there were no significant statistical differences between treatment and placebo groups. There were negligible adverse reactions to the bright green light, which was well tolerated.ConclusionBright green light was not shown to have an antidepressant effect in the age group of this study, but a larger trial with brighter green light might be of value.

Type III home sleep testing versus pulse oximetry: is the respiratory disturbance index better than the oxygen desaturation index to predict the apnoea-hypopnoea index measured during laboratory polysomnography?

Objectives In its guidelines on the use of portable monitors to diagnose obstructive sleep apnoea, the American Academy of Sleep Medicine endorses home polygraphy with type III devices recording at a minimum airflow the respiratory effort and pulse oximetry, but advises against simple pulse oximetry. However, oximetry is widely available and simple to use in the home. This study was designed to compare the ability of the oxygen desaturation index (ODI) based on oximetry alone with a stand-alone pulse oximeter (SPO) and from the oximetry channel of the ApneaLink Plus (ALP), with the respiratory disturbance index (RDI) based on four channels from the ALP to predict the apnoea–hypopnoea index (AHI) from laboratory polysomnography. Design Cross-sectional diagnostic accuracy study. Setting Sleep medicine practice of a multispecialty clinic. Participants Patients referred for laboratory polysomnography with suspected sleep apnoea. We enrolled 135 participants with 123 attempting the home sleep testing and 73 having at least 4 hours of satisfactory data from SPO and ALP. Interventions Participants had home testing performed simultaneously with both a SPO and an ALP. The 2 oximeter probes were worn on different fingers of the same hand. The ODI for the SPO was calculated using Profox software (ODISOX). For the ALP, RDI and ODI were calculated using both technician scoring (RDIMAN and ODIMAN) and the ALP computer scoring (RDIRAW and ODIRAW). Results The receiver–operator characteristic areas under the curve for AHI ≥5 were RDIMAN 0.88 (95% confidence limits 0.81–0.96), RDIRAW 0.86 (0.76–0.94), ODIMAN 0.86 (0.77–0.95), ODIRAW 0.84 (0.75–0.93) and ODISOX 0.83 (0.73–0.93). Conclusions We conclude that the RDI and the ODI, measured at home on the same night, give similar predictions of the laboratory AHI, measured on a different night. The differences between the two methods are small compared with the reported night-to-night variation of the AHI.

Daily light exposure among psychiatric inpatients

1. The light environment is a key element in the restoration and maintenance of health. 2. People need exposure to bright light (greater than 2,000 lux) to synchronize their circadian rhythms. 3. The affective state of people is related to their light exposure. 4. Bright light among psychiatric inpatients is low. Interventions to increase light exposure in therapeutic environments and individual care plans are recommended.