Derek N. Eder

Dawn simulation and bright light in the treatment of SAD: a controlled study

BACKGROUND Some small controlled studies have found that dawn simulation is effective in treating seasonal affective disorder (SAD). With a larger sample size and a longer duration of treatment, we compared dawn simulation with bright light therapy and a placebo condition in patients with SAD. METHOD Medication-free patients with SAD were randomly assigned to one of three conditions: bright light therapy (10,000 lux for 30 min, from 6:00 AM to 6:30 AM), dawn simulation (1.5 hour dawn signal from 4:30 AM to 6:00 AM peaking at 250 lux), and a placebo condition, a dim red light (1.5 hour dawn signal from 4:30 am to 6:00 AM peaking at 0.5 lux.) Over the subsequent 6 weeks, the subjects were blindly rated by a psychiatrist using the Structured Interview Guide for the Hamilton Depression Rating-Seasonal Affective Disorder Version (SIGH-SAD). We modeled the profiles of the remissions (SIGH-SAD < or = 8) and response (> or =50% decrease in SIGH-SAD) to treatment over time using Cox proportional hazards models. RESULTS The sample consisted of 95 subjects who were randomized to the three conditions: bright light (n = 33), dawn simulation (n = 31) and placebo (n = 31). Dawn simulation was associated with greater remission (p <.05) and response (p <.001) rates compared to the placebo. Bright light did not differ significantly from the placebo. Dawn simulation was associated with greater remission (p <.01) and response (p <.001) rates compared to the bright light therapy. The mean daily hours of sunshine during the week before each visit were associated with a significant increase in likelihood of both remission (p <.001) and response (p <.001). CONCLUSIONS Dawn simulation was associated with greater remission and response rates compared to the placebo and compared to bright light therapy. The hours of sunshine during the week before each assessment were associated with a positive clinical response.

Nocturnal pulse wave attenuation is associated with office blood pressure in a population based cohort

OBJECTIVE AND BACKGROUND Pulse wave amplitude (PWA) derived from the digital vascular bed has been used in sleep studies. The nocturnal attenuation of PWA has been shown to reflect sympathetic activation during sleep. We assessed the relationship between nocturnal PWA attenuation and office blood pressure (BP). METHODS Eighty-one subjects (46 men; age 60+/-7 years; body mass index [BMI] 28.2+/-4.3 kg/m(2); apnea hypopnea index [AHI], 25.4+/-22.6 events/h; systolic BP 137+/-15 mm Hg; diastolic BP 79+/-7 mm Hg) recruited from a population based cohort underwent simultaneous ambulatory polysomnography (PSG) and peripheral arterial tonometry (PAT) recording. Episodic attenuations of PWA derived from the pulse waveform of the PAT signal were identified and characterized. Generalized least squares regression models were used to identify the associations between median PWA attenuation (PWA.att), office BP and sleep-related disordered breathing. RESULTS We found that the association between PWA.att and office BP was independent of gender, age, BMI, antihypertensive medication, number of attenuation episodes, AHI, oxygen desaturation 4% index (ODI4) and arousal index. Each 10% increase in PWA.att was associated with increases of 5.0 mm Hg systolic BP (P=0.02) and 3.0 mm Hg diastolic BP (P=0.005). We also found independent relationships between systolic/diastolic BP and BMI (P=0.0006/0.001), AHI (P=0.03/0.1) and ODI4 (P=0.03/0.03). CONCLUSIONS The degree of PWA attenuation during the night is associated with office BP independent of sleep-disordered breathing. Continuous assessment of PWA during sleep may provide novel insights into cardiovascular physiology and morbidity.

Oximeter-Based Autonomic State Indicator Algorithm for Cardiovascular Risk Assessment

BACKGROUND Cardiovascular (CV) risk assessment is important in clinical practice. An autonomic state indicator (ASI) algorithm based on pulse oximetry was developed and validated for CV risk assessment. METHODS One hundred forty-eight sleep clinic patients (98 men, mean age 50 ± 13 years) underwent an overnight study using a novel photoplethysmographic sensor. CV risk was classified according to the European Society of Hypertension/European Society of Cardiology (ESH/ESC) risk factor matrix. Five signal components reflecting cardiac and vascular activity (pulse wave attenuation, pulse rate acceleration, pulse propagation time, respiration-related pulse oscillation, and oxygen desaturation) extracted from 99 randomly selected subjects were used to train the classification algorithm. The capacity of the algorithm for CV risk prediction was validated in 49 additional patients. RESULTS Each signal component contributed independently to CV risk prediction. The sensitivity and specificity of the algorithm to distinguish high/low CV risk in the validation group were 80% and 77%, respectively. The area under the receiver operating characteristic curve for high CV risk classification was 0.84. β-Blocker treatment was identified as an important factor for classification that was not in line with the ESH/ESC reference matrix. CONCLUSIONS Signals derived from overnight oximetry recording provide a novel potential tool for CV risk classification. Prospective studies are warranted to establish the value of the ASI algorithm for prediction of outcome in CV disease.

A double-blind, crossover study of Doxazosin and Enalapril on peripheral vascular tone and nocturnal blood pressure in sleep apnea patients

OBJECTIVE Pulse wave attenuation, which occurs in association with obstructive sleep apnea (OSA), is sympathetically mediated. We compared the effect of Doxazosin (DO, a peripheral alpha-receptor inhibitor) and Enalapril (EN, an ACE inhibitor) on digital vasoconstriction and nocturnal blood pressure (BP) in hypertensive OSA patients. METHODS A double-blind, crossover study comparing equipotent dosages of DO (4 mg/day for 2 weeks with 8 mg/day for an additional 2 weeks) and EN (10mg/day and 20mg/day, respectively) was undertaken in 16 male OSA patients (age 55+/-7 years, body mass index 30.1+/-3.8 kg/m(2)) with hypertension. Assessments including ambulatory 24-h BP, full-night polysomnography with simultaneous peripheral arterial tone (PAT) and beat-to-beat finger BP monitoring (Finapres) were made at the end of each treatment period. Nighttime BP and digital vasoconstrictions associated with apneic events (measured as the ratio of PAT amplitudes during and after apneas) were analyzed. RESULTS There were no differences between the two treatments in the 24-h BP profile and OSA severity. But the nighttime average beat-to-beat finger BP was significantly higher under DO treatment (systolic BP 129+/-13 vs. 119+/-23 mm Hg, P=0.02; diastolic BP 81+/-12 vs. 74+/-14 mm Hg, P=0.04, DO and EN respectively). In a linear mixed effects regression model, the PAT ratio during apnea increased 5.3% under DO compared with EN (P<0.0001). Each percentage decrease of apneic related oxygen desaturation was associated with 0.9% decrease in the PAT ratio (P<0.0001). REM sleep was associated with 2.2% decrease of PAT ratio compared to NREM sleep (P=0.002). CONCLUSION Digital vasoconstrictions associated with apneic events are alpha-receptor mediated. DO compared to EN has a proportionally poor effect on nocturnal BP control in OSA patients, which may be due to the enhanced sympathetic nervous system activity characteristic of this condition.

Selective alterations of the first NREM sleep cycle in humans by a dopamine D1 receptor antagonist (NNC-687).

This paper details the first study of the effects of dopamine D1 receptor antagonism on the regulation of human sleep EEG (electroencephalogram). The investigational drug NNC-687 (NNC 01-0687/CEE 03-310) was administered to 20 healthy young men in doses of 5, 10, and 15 mg in a double blinded, placebo controlled, crossover design. In rats, dopamine D1 receptor antagonism can produce large increases in the amounts of both rapid eye-movement (REM) and non-rapid eye-movement (NREM) sleep. In this study, drug effects were most prominent in the first NREM period. D1 antagonism markedly reduced the peak-amplitude of delta EEG waves but increased their instantaneous frequency as well as enhancing the total number, incidence, and burst-duration of sleep spindles. The length of the first NREM period was increased up to 47% over baseline. Despite these large increases in NREM sleep time, the amount of delta EEG power accumulated over the first NREM period was conserved at baseline levels. We note that the sleep-EEG profile of D1 antagonism is very similar to that of GABAA (gamma-aminobutyric acid) receptor modulators and suggest that D1 antagonism may alter the properties of the neuronal networks which generate delta and spindle, and K-complex EEG waveforms through the upstream modulation of GABAA receptor activity.

A seasonal and circadian study of suicide over a 10-year period in the Seattle area

reduction of REM % (17 + 2, 15 +_ 5, respectively) when compared with Dex0 (20 + 5). There was no effect of Dex on the latency to REM, number of REM period or REM activity. A significant main effect of Dex was shown on the mean MSLT (p < 0.01). Dex I and Dex2 resulted in an increased level of alertness (14.9 _+ 2.8 and 15.7 _+ 1.8) when compared to Dex0 (12.2 _+ 3.6) The suppression of the HPA axis, by the exogenous administration of corticosteroids, resulted in an increased level of alertness. Whether this was the result of REM suppression, as shown in REM deprivation studies, or due to a direct effect on the mechanisms that control alertness remains to be elucidated.