Mortality risk of major depression.
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Biomedical subjects
Publications and source records attributed to D F Kripke.
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The authors measured ambient illumination exposure in healthy volunteers in San Diego, California (latitude 32 degrees 43' N, n = 30), and Rochester, Minnesota (latitude 44 degrees 1' N, n = 24), during each of the four quarters of the year, which were centered on the solstices and equinoxes. Subjects wore photosensors on their wrists and lapels (or foreheads while in bed) 24 h per day for an average of 5-6 days per quarter. The maximum of the two illumination readings was stored each minute. Annual average time spent per day in outdoor illumination (> or = 1000 lux) was significantly higher in San Diego than it was in Rochester (p < .04). Daily durations of illumination at or exceeding thresholds of 1, 10, 100, 1000, and 10,000 lux were highly seasonal in the sample as a whole (p < .01 at 1 lux, p < .0001 at other thresholds). Seasonal variation in outdoor illumination was far more pronounced in Rochester than it was in San Diego (interaction p < .001) but remained significant in San Diego (p < or = .03). Seasonal variation in indoor illumination was generally similar in the two cities. The median Rochester subject experienced illumination > or = 1000 lux for 2 h 23 min per day during summer and 23 min per day during winter. The corresponding times in San Diego were 2 h 10 min and 1 h 20 min. Neither age nor gender predicted illumination duration at any level. Both season and geographic location strongly influenced human illumination exposure, and behavior (choice of indoor vs. outdoor environment) was the most important mediating factor.
We explored the illumination exposure of middle-aged adults to determine normal values and to explore several correlates of daily light exposures. Subjects aged 40-64 years in San Diego, CA were recruited by random telephone dialing. Subjects completed a demographic interview and the Center for Epidemiologic Studies Depression self-rating scale (the CES-D) supplemented with eight questions related to seasonal affective disorders (SAD). Data were analyzed for 106 volunteers who wore a device that monitors illumination exposures and activity. The median subject was exposed to illumination > or = 1000 lux for only 4% of the time observed, that is, only about 58 min per day were spent in daylight. Subjects scoring higher on the atypical SAD mood symptoms spent less time in bright illumination rs = -0.266, p = 0.003. The CES-D depression score was similarly correlated with illumination but of borderline significance (rs = -0.150, p = 0.063). These results suggest the hypothesis that many Americans may be receiving insufficient light exposure to maintain optimal mood.
The period of the circadian rhythm of wheel-running was shortened when golden hamsters were given supplemental dietary potassium or rubidium for two weeks. Treatment with 4-aminopyridine, a potassium channel blocker, significantly increased circadian period. These period changes (0.17 h for potassium treatment, 0.14 h for rubidium, and 0.07 h for 4-aminopyridine) support previous data indicating that potassium is a component of the mammalian biological clock mechanism.
Since the turn of the century, there have been numerous publications on the seasonality of suicide. Rarely has the duration of sunlight exposure or any other weather parameter been quantitated in studies of suicide seasonality. To explore the relationships between sunlight and suicide, we examined California weather and suicide data from 1968 to 1977. Los Angeles County and Sacramento County were well-suited to the investigation, as complete data were available for these large population centers. There was no evidence of seasonality to suicides in L.A. County or Sacramento, despite a pronounced seasonality to weather. To investigate the acute temporal effects of weather on suicides, all occurrences of 10 successive above- or below-average sunshine days were identified. Suicides of for intervals of 5 days were then compared by Mann-Whitney analyses for 25 days after the selected intervals. For L.A. County, there were no significant findings. For Sacramento County, however, there was evidence for sunlight inhibition of suicides at days 21-25 after the above-average sunshine. Suicides after 10 days of below-average sunshine were increased as much as 70% about the 10-year average. Further replication studies with larger data sets are needed for an adequate examination of the correspondences of suicide data and weather measurements.
The circadian wheel-running rhythm of golden hamsters was monitored during chronic oral treatment with four antidepressants and two potentially depressogenic agents. Desmethylimipramine shortened the circadian period (tau) by 0.1 hour. In contrast, clorgyline lengthened tau by 0.1 hour and delayed light-synchronized wheel-running rhythms by 1.4 hour. Phenelzine, fluoxetine, clonidine, and propranolol did not significantly alter light-entrained phase or free-running period over a range of doses. Other rhythm parameters were also unaffected by antidepressant or depressogenic drugs. These data suggest that mood-altering drugs do not consistently influence circadian rhythms in the hamster.
This study was designed to determine the impact of central sleep apnea with or without Cheyne-Stokes respiration (CSR) on morbidity and mortality. Central sleep apnea was found in 77 male general medical ward in-patients. Cheyne-Stokes respiration was found in 49 of the 77 men; in 15 men, CSR was severe, ie, > or = 25 percent of the night spent in CSR, in 34 men CSR was mild (1 to 25 percent CSR). Twenty-eight men had central sleep apnea but no CSR. An additional 31 patients had no sleep apnea and no CSR. The patients with severe CSR had more central apneas, more, but shorter desaturations, more awakenings and more wake time during the night, but spent more time in bed than those with no CSR or no apnea. Radiographic evidence was consistent with an association of CSR and heart failure. In addition, patients with severe CSR were at almost twice the risk of dying compared with those with no apnea and had a shorter survival time. Nevertheless, we could not confirm that CSR was an independent predictor of elevated mortality risk, implying that some other factors specific to severe CSR predispose these patients to shorter survival time.
Polygraphic sleep recordings were compared between patients with primary major depression (MDD), patients with primary alcoholism and secondary MDD, and normals. Patients differed significantly from normals on the following measures: both patient groups showed short REM latency, and REM latency corrected, along with prolonged sleep latency. Secondary depressives differed from controls on several other measures: sleep onset time, total sleep time, delta sleep, REM percent, stage one sleep, stage three sleep, non-REM sleep, stage three and delta sleep in the first non-REM period. Prior research has shown a decrease in non-REM sleep and total sleep time in alcoholic patients who are not currently depressed, and short REM latency in patients with MDD. Thus, our findings suggest an additive effect of two disorders known to affect sleep: alcoholism and depression.
Mild sleep disordered breathing is very common in the elderly, but little is known about the course of the disorder over time. Twenty-four elderly people from a population-based study were recorded three times over an 8.5-year period. There were no significant changes in either apnea index or in respiratory disturbance index (RDI) over time, even when controlled for body mass index. For most subjects, there was great variability over time in the number of respiratory disturbances. The sensitivity of RDI > or = 15 at visit 1 predicting RDI > or = 15 at visit 3 was only 20%. The predictive value was 50%. Sleep disordered breathing measured at a single point in time is rather weakly predictive of the severity of breathing disorder 4-8 years later.
Lithium can be toxic to rodents at plasma concentrations (0.6-1.2 mmol/L) that also phase delay circadian rhythms. In hamsters, raising the concentration of calcium in the diet from 0.1%-3% reduced weight loss and polydipsia caused by 0.4% lithium carbonate. Calcium ingestion did not affect plasma lithium concentration or the phase of the circadian wheel-running rhythm in lithium-treated animals. Calcium ingestion did not alter weight gain, salt or water intake, or circadian rhythms in hamsters not receiving lithium. Dietary calcium supplementation may prevent some toxic effects of lithium without interfering with other central nervous system actions.
Psychotropic drug-free hospitalized veterans with nonseasonal major depressive disorders or depressed forms of bipolar disorder were treated with light for 1 week. Twenty-five patients were randomly assigned to bright white light treatment (2000-3000 lux), and 26 patients were randomized to dim red light placebo control treatment. Unlike those treated with dim red light, those treated with bright white light showed declines in three measures of depression during treatment. Partial relapse appeared within 2 days. A global depression score showed a statistically significant (p = 0.02) difference favoring bright white light treatment. Two bright-light-treated patients became mildly hypomanic, but side effects were mild. Improvement was not correlated with patient expectations; indeed, patients expected somewhat greater benefit from the placebo. Patients treated in summer responded as well as those treated in winter. Baseline electroencephalogram (EEG) sleep stage data (e.g., rapid eye movement; REM latency) did not predict treatment responses. These 1-week treatment results suggest that bright light might produce benefits for patients with nonseasonal depression. Bright light should not be recommended for routine clinical application before additional assessments with longer treatment durations are done.
The purpose of this study was to develop and validate automatic scoring methods to distinguish sleep from wakefulness based on wrist activity. Forty-one subjects (18 normals and 23 with sleep or psychiatric disorders) wore a wrist actigraph during overnight polysomnography. In a randomly selected subsample of 20 subjects, candidate sleep/wake prediction algorithms were iteratively optimized against standard sleep/wake scores. The optimal algorithms obtained for various data collection epoch lengths were then prospectively tested on the remaining 21 subjects. The final algorithms correctly distinguished sleep from wakefulness approximately 88% of the time. Actigraphic sleep percentage and sleep latency estimates correlated 0.82 and 0.90, respectively, with corresponding parameters scored from the polysomnogram (p < 0.0001). Automatic scoring of wrist activity provides valuable information about sleep and wakefulness that could be useful in both clinical and research applications.
The suppression of melatonin by bright light is probably mediated by the suprachiasmatic nucleus (SCN) in humans. In animals, SCN cells have broad visual receptive fields, suggesting that peripheral bright light could be effective for melatonin suppression. Twelve healthy subjects were subjected to 1000 lux illumination for 2 hr from 0100 to 0300 on two occasions: once lighting the central visual field 5 degrees from the center of gaze and once lighting the peripheral visual field 60 degrees lateral to the direction of gaze. Six subjects were observed on a third occasion in dim light. The three conditions differed significantly, with less melatonin secreted in 1000 lux, but melatonin levels with central and peripheral illumination did not differ. This suggests that phototherapy using bright light in the visual periphery may be effective.
OBJECTIVE: The authors' objective was to test the hypothesis that fatigue affects the activities and employment of subjects with HIV infection and that indices of immunosuppression and inflammation may have statistical utility in predicting fatigue and sleep disturbance. METHOD: The authors prospectively asked 112 homosexual men (62 HIV-seropositive subjects and 50 HIV-seronegative comparison subjects) to complete a questionnaire on fatigue and sleep disturbance. In addition, hematocrit, WBC count, CD4+ cell number, lactate dehydrogenase, albumin, and total globulin were measured. RESULTS: For HIV-seropositive patients fatigue was significantly more of a problem and interfered more with important activities such as employment and driving than with seronegative comparison subjects. The HIV-infected patients were significantly more likely to be unemployed, to feel fatigued through more hours of the day, to sleep more, to nap more, and to have diminished midmorning alertness. The medical variables could be used to statistically predict fatigue, its interference with daily activities, and employment. CONCLUSIONS: Fatigue and sleep disturbances contribute to morbidity and disability in HIV-infected homosexual men, especially those in CDC stage IV (AIDS-related complex or AIDS). Correlation with measures of immunosuppression and inflammation and comparison between fatigued versus nonfatigued groups suggest the possibility of statistical prediction of fatigue by using these measures. Further study is needed to examine the possibility of eventual specific intervention to clinically treat HIV-related fatigue, sleepiness, and sleep disturbance.
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.
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Quality of sleep influences the level of daytime functioning, including stress levels, psychosomatic complaints, general health, and overall well-being. As people age, they complain more about disturbed sleep, insomnia, increased time in bed, and sleep fragmentation. These complaints can be related to circadian rhythm desynchronization, hypnotic or other medication use, chronic bedrest, napping, dementia, or to sleep apnea, a disorder of respiratory cessation which is quite prevalent in the elderly. We review here the results of 12 years of research on sleep in the elderly. In studies of three populations of elderly, it was found that between 24% and 42% had five or more apneas per hour of sleep and 4%-14% had 20 or more apneas per hour of sleep. Since apnea is related to dementia and even to mortality, this high prevalence of apnea is of extreme importance.
Effects of depression and age on the Horne-Ostberg morningness-eveningness scale in human volunteers were assessed. Thirty-nine healthy outpatients with current DSM-IIIR depression, free of recent substance abuse or confounding medications, were compared to 39 age- and sex-matched controls. Patients reported greater 'eveningness' than controls (P = 0.014, Wilcoxon signed-ranks test). There was multimodality in the distribution of Horne-Ostberg scale scores in the depressed group, but a normal distribution in controls. Pearson's correlation of age vs. Horne-Ostberg score was positive (r = 0.42-0.55). Depression and age influence the Horne-Ostberg score. Potential multimodality of circadian phase in the depressed group deserves further study.