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Biomedical subjects

D A Sack

Publications and source records attributed to D A Sack.

At least 145 records · Page 8Linked to original sources

Phototherapy of seasonal affective disorder. Time of day and suppression of melatonin are not critical for antidepressant effects.

Seasonal affective disorder is characterized by recurring cycles of fall-winter depression and spring-summer hypomania (or euthymia). In winter, depressed patients with seasonal affective disorder respond to daily treatments with five to six hours of bright artificial light in two to three days. They relapse two to three days after light is withdrawn. In this study carefully controlled experimental conditions were used to determine whether phototherapy acts via a photoperiodic mechanism in which the timing of light is critical for its therapeutic effect. Photoperiodism is a common regulatory mechanism in animal seasonal rhythms and depends for its effect on light-induced changes in the pattern of nocturnal melatonin secretion. The results reported herein of "skeleton photoperiod" experiments indicate that the efficacy of phototherapy may not depend on its timing or its effect on melatonin secretion.

Circadian Rhythm↗

A psychophysiological study of insomnia.

Ten insomniacs with age- and sex-matched controls had studies of baseline sleep, relation of polygraphically defined sleep to retrospective reports, and arousal thresholds to electronic tones or to a recording of a voice calling out the subject's name. The two groups differed in 10 out of 13 questions about habitual sleep and daytime feelings. In contrast, polygraphic measures of baseline sleep indicated only that insomniacs tended to have slightly less total sleep and had a small but significant increase in early morning awakening time. Unlike the descriptions of habitual sleep, the subjects' retrospective reports of the previous night's sleep differed significantly only for the variable of total sleep time, and there were virtually no differences in the description of their status at a given moment. Auditory arousal thresholds were similar in the two groups, and both went back to sleep and stayed asleep with equal facility. These findings suggest that subjectively poor sleep is not necessarily "light" sleep. For both groups, arousal thresholds differed across the sleep stages, and thresholds to hearing the subject's name were lower than those in response to electronic tones. Although insomniacs had as much polygraphically defined sleep as controls between the forced awakenings of the arousal threshold studies, they perceived their sleep to be only approximately half as long. Insomniacs described themselves as having been awake more frequently than controls in 8 out of 10 forced awakening situations. In one case, insomniacs also overestimated the time between awakenings. In both groups, there was little relationship between reported habitual aspects of sleep and baseline polygraphically defined sleep variables. On questionnaires the following mornings, however, in both groups there was a positive correlation of subjective quality of sleep on the baseline nights with percentage of rapid eye movement sleep, and a negative correlation to various aspects of slow-wave sleep.

Adult↗

Vitamin B12 deficiency and the dexamethasone suppression test.

The authors describe dexamethasone nonsuppression in a depressed patient with a vitamin B12 deficiency. After B12 replacement there was no change in the patient's clinical state. However, the dexamethasone suppression test normalized. Thus, dexamethasone nonsuppression in this patient seemed to be more closely related to vitamin B12 deficiency than to affective state.

Depressive Disorder↗

Melatonin in seasonal affective disorder and phototherapy.

In several studies we have found that treatment with bright environmental light, capable of suppressing human melatonin, reverses the winter depressive symptoms of patients with seasonal affective disorder (SAD), whereas light too dim to suppress human melatonin is therapeutically ineffective. This finding, as well as the central importance of melatonin as a hormonal mediator of photoperiodic changes on seasonal rhythms in animals, led us to test the hypothesis that melatonin mediates the effects of shortening days on the winter symptoms of SAD and that the modification of melatonin secretion by bright light mediates its antidepressant effects. We partially reversed the antidepressant effects of phototherapy in 8 SAD patients by oral melatonin administration, but in another study of 19 SAD patients we failed to find any therapeutic difference between the beta-adrenergic blocker, atenolol, which inhibits melatonin secretion, and placebo. In a third study of 7 SAD patients we showed that the anti-depressant effects of phototherapy were not photoperiodic and appeared to be independent of melatonin suppression. There is some preliminary evidence that melatonin secretion may be abnormal in SAD. We conclude that while melatonin may play some role in the symptoms of SAD and the effects of phototherapy, it cannot by itself account for these phenomena.

Animals↗

Liberation of hydrogen from gastric acid following administration of oral magnesium.

We are in the process of developing a noninvasive test for gastric acid secretion based on the reaction of orally administered magnesium metal with gastric acid: Mg + 2HCl in equilibrium with MgCl2 + H2. We hypothesized that the hydrogen gas thus evolved could be detected in exhaled air and belches and that the amount of hydrogen released could be related to the amount of acid in the stomach. To validate this hypothesis, we gave magnesium to two groups of young adult volunteers following either betazole stimulation or cimetidine inhibition of acid secretion. In group I we gave subcutaneous betazole and gave magnesium in doses from 10 to 200 mg. In group II we gave oral betazole and used a constant dose of 150 mg of magnesium. In both groups we consistently detected significant increases in breath and belch hydrogen following magnesium in the betazole-stimulated volunteers. This response was blocked by cimetidine. The magnitude of the response was related to the magnesium dose, with 150 mg appearing to induce a maximum response. Administration of oral magnesium up to 200 mg was not associated with any untoward effects. We conclude that magnesium led to the release of hydrogen gas in vivo and that the quantity of hydrogen gas recovered was related to the amount of gastric acid. With further development, this principle might be used to develop a simple noninvasive test for gastric acid secretion.

Adult↗

Sleep and circadian rhythms in affective patients isolated from external time cues.

Sleep electroencephalographic activity, circadian rhythms in motor activity and rectal temperature, and clinical state were monitored longitudinally in four affectively ill patients (two depressed, one manic, and one rapidly cycling between depression and mania) who lived in isolation from external time cues (zeitgebers) for 3 to 4 weeks. In these conditions it was possible to observe the intrinsic or free-running behavior of circadian pacemakers and thereby to test several hypotheses about the role of sleep and circadian rhythms in the pathogenesis of depression. No hypothesis was consistently supported by the results. We found that the intrinsic rhythm of a circadian pacemaker appeared to free-run with an abnormally fast frequency in one patient. No patient remained stably depressed during temporal isolation. Our experience suggests that this type of study can be carried out safely with appropriate precautions. Temporal isolation is a means to test decisively predictions of several chronobiological hypotheses about affective illness and should be applied to additional patients.

Adult↗

Antidepressant effects of sleep deprivation in bright and dim light.

In order to test whether exposure to bright artificial light at night is a necessary condition for the antidepressant response to sleep deprivation therapy, five patients were totally sleep-deprived on two separate nights, once in very bright light and once in nearly total darkness. During the day after the sleep-deprivation night patients were found to have responded equally well to sleep deprivation in both conditions. During the sleep-deprivation night, however, antidepressant responses may have been greater in the bright light condition. Thus, light at night is not necessary for the antidepressant response to sleep deprivation, but we cannot rule out the possibility that the effects of light exposure and sleep deprivation are additive or that exposure to light at some time after sleep deprivation begins (including during the following day) is necessary for the response.

Adult↗

Psychoses associated with bupropion treatment.

The authors describe the development of acute psychoses in four patients treated with bupropion, a unicyclic aminoketone antidepressant. In two of the cases the psychoses seemed to be affected by dose. The mechanism responsible for the psychotic reactions is unclear, although it may involve perturbation of dopaminergic systems. On the basis of their experience, the authors offer recommendations regarding the clinical use of bupropion.

Acute Disease↗

Antidepressant effects of light in seasonal affective disorder.

The authors treated winter depression in 13 patients with typical seasonal affective disorder by extending the length of winter days with bright and dim light in the morning and evening in a balanced-order crossover study. Bright light had a marked antidepressant effect, whereas the dim light did not. This response could not be attributed to sleep deprivation. Subsequent pilot studies indicated that bright evening light alone is probably also effective. Several patients were able to maintain the antidepressant response throughout the winter months by continuing daily light treatments.

Adult↗

Potentiation of antidepressant medications by phase advance of the sleep-wake cycle.

Four patients with major depression who were unresponsive to antidepressant medications rapidly improved and remained euthymic after an advance of the sleep-wake cycle. Phase advance of the sleep-wake cycle and antidepressant treatment may have complementary effects on the circadian system. The authors suggest that the combination may be useful in treating drug nonresponders and in hastening response to antidepressant drugs.

Adult↗

Which veterans go to VA psychiatric hospitals for care: a pilot study.

In a study to determine whether certain factors could predict whether veterans seek psychiatric care at a Veterans Administration psychiatric hospital or at other public hospitals, data were collected on 644 visits by veterans to one VA psychiatric hospital and two non-VA public hospitals. Race, alcoholism, number of presenting problems, kind of prior psychiatric hospitalizations, and whether the disability was service-connected were significant factors in distinguishing veterans seeking psychiatric care at the different hospitals. Age, marital status, income, and transiency were not important factors. Minority status and alcoholism appeared to be independent of each other in predicting greater use of the VA hospital.

Adult↗

Treatment of seasonal affective disorder with light in the evening.

A cross-over comparison study of exposure, in the evenings only, to bright versus dim light was carried out on nine female patients with seasonal affective disorder. A significant antidepressant effect of the bright lights was shown. No consistent observable effects were produced by the dim lights. These results support earlier studies demonstrating the efficacy of bright light given morning and evening. The antidepressant effect of light is not mediated by sleep deprivation, and the early morning hours are not crucial for a response.

Adult↗

Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy.

Seasonal affective disorder (SAD) is a syndrome characterized by recurrent depressions that occur annually at the same time each year. We describe 29 patients with SAD; most of them had a bipolar affective disorder, especially bipolar II, and their depressions were generally characterized by hypersomnia, overeating, and carbohydrate craving and seemed to respond to changes in climate and latitude. Sleep recordings in nine depressed patients confirmed the presence of hypersomnia and showed increased sleep latency and reduced slow-wave (delta) sleep. Preliminary studies in 11 patients suggest that extending the photoperiod with bright artificial light has an antidepressant effect.

Adult↗

Mucosal antitoxic and antibacterial immunity after cholera disease and after immunization with a combined B subunit-whole cell vaccine.

Mucosal and systemic immune responses to a new oral cholera vaccine, consisting of the B subunit plus killed vibrios, were studied in Bangladeshi volunteers and compared with those to clinical cholera. A single peroral dose of vaccine induced a local IgA antitoxin response in intestinal-lavage fluid of seven of eight vaccinees; the response closely mimicked that of patients convalescing from cholera, and evidence of the induction of local immunologic memory was found as well. Two peroral doses were needed for stimulation of an intestinal IgA immune response to the lipopolysaccharide of Vibrio cholerae that was comparable to the response obtained after clinical cholera. This response to peroral immunization was considerably stronger than that to parenteral vaccination, although the intramuscular route gave rise to the strongest IgG antitoxin and antilipolysaccharide responses in serum. The results suggest that B subunit-whole cell vaccine, when given in at least two oral doses, may be a good candidate for use in cholera prophylaxis.

Administration, Oral↗

Local and systemic antibody responses and immunological memory in humans after immunization with cholera B subunit by different routes.

A single oral or intramuscular immunization with purified cholera B subunit induced an intestinal secretory immunoglobulin A (IgA) antitoxin response in, respectively, 10 out of 11 and 9 out of 12 Bangladeshi volunteers. The IgA titre rise in intestinal lavage fluid was similar by either route of immunization, but the duration of the response was usually longer after the oral dose. A second immunization by either route, given 25 days after the first, and a third dose (oral only), given 15 months later, resulted in intestinal immune responses which did not differ in magnitude from that induced by the initial immunization but were observed significantly earlier, usually by day 3. Both the first oral and intramuscular immunizations induced significant antitoxin titre rises, mainly IgG, in the serum in most vaccinees but the magnitude of the response was considerably higher after the intramuscular dose. Significant IgA antitoxin titre rises in saliva and breast milk were seen after both oral and intramuscular immunization.

Administration, Oral↗