Melatonin in light treatment of patients with seasonal and nonseasonal depression

Melatonin as a marker of circadian rhythm and the effect of bright light on melatonin were studied in 63 depressed patients, 42 with a seasonal pattern and 21 with a nonseasonal pattern. The patients were matched for age, time of treatment and severity of depression. Before light treatment, blood was sampled for melatonin and depression was clinically rated with the Comprehensive Psychopathological Rating Scale and Hamilton Depression Rating Scale. Two hours of light treatment, 350 cd/m2, was given daily for 10 days 0600 to 0800 or 1800 to 2000. Of the 42 patients with seasonal depression, 26 were treated with morning light and, 16 with evening light. The melatonin amplitude was significantly decreased by light, and the melatonin phase position was advanced by morning light and delayed by evening light. All patients except for 3 in each group changed in the expected direction. Although the patients with seasonal pattern had a more favorable outcome than patients with nonseasonal pattern, there was no difference in therapeutic outcome related to the baseline melatonin phase position. The hypothesis that the short term clinical effects of light therapy either in the morning or evening are related to pretreatment melatonin levels or alteration of melatonin amplitude or phase position was not supported in the study. There was also no significant difference between the seasonal and nonseasonal patients related to the degree of light suppression of melatonin and the rebound effect of serum melatonin levels following bright level exposure between 2200 and 2300 before regular light treatment.     

Negative attributional style in seasonal and nonseasonal depression

OBJECTIVE: There is a substantial relationship between dysfunctional cognitions and the clinical course of major depression. This study examined whether this association extends to patients with seasonal affective disorder. METHOD: A revised version of the Attributional Style Questionnaire was used to assess negative attributional style and predict response to treatment in a group of depressed outpatients, 26 with seasonal depression and 30 with nonseasonal, unipolar major depression. RESULTS: Pretreatment scores on negative attributional style did not differ between the patients with seasonal affective disorder and those with nonseasonal depression. Negative attributional style predicted poor response to pharmacotherapy in the nonseasonal depression group but did not predict response to light therapy in the group with seasonal affective disorder. CONCLUSIONS: Dysfunctional cognitions may play a lesser role in seasonal affective disorder than in nonseasonal depression.     

Melatonin and biological rhythms

The purpose of this study was to examine the influence of cognitive function and other biopsychosocial factors on test-retest agreement, four-week variability, and intensity of self-reported pain using the verbal 0 to 10 scale and a pain thermometer in 115 nursing home residents over four weeks. Pain was assessed twice on three days during week 1, and once each during weeks 2, 3 and 4. A forward stepwise regression procedure was used to examine the influence of biopsychosocial parameters (age, race, gender, educational status, marital status, comorbidity, cognitive function, depression, social support, physical function and self-rated health) on pain intensity, test-retest agreement and variability. There was a quadratic association between cognitive function and test-retest agreement with the 0-10 scale; residents with Folstein scores of 22-26 were more likely to show disagreement (50% of 34) than residents with scores < 22 or > 26 (7% of 71). Higher Folstein scores were also associated with greater pain intensity for both pain scales (p < 0.001). Baseline pain intensity was significantly related to pain variability (0-10 scale only). The clinician should be cognizant of these relationships when interpreting verbalizations of pain in long-term care facilities.     

Melatonin: role in development

Melatonin is the mammalian fetus's window to periodicity of the outside world. Through melatonin, the fetus "knows" what time of year it is and, in all likelihood, also knows the time of day. The best known function of melatonin during development is to communicate information about photoperiod and thereby adaptively regulate reproductive development. A second likely function of melatonin during development, which may be related to but more widespread than the first, is to entrain the developing circadian pacemaker. Prenatal maternal entrainment occurs in all of the eutherian mammals in which it has been examined, and in Syrian hamsters exogenous melatonin during development causes entrainment. The broader distribution and greater abundance of melatonin receptors during development, relative to mature animals, suggests that developmental effects of melatonin are greater and more diverse. The human fetal suprachiasmatic nucleus expresses melatonin binding sites and is therefore likely to be affected by both endogenous and exogenous melatonin with consequences for the prenatal and postnatal expression and entrainment of circadian rhythms. Caution is warranted, not only concerning the use of exogenous melatonin during pregnancy and lactation but also concerning behavior that might disrupt the mother's endogenous melatonin rhythm.     

Melatonin: a popular hormone

This contribution makes an attempt to critically reassess the impressive career of melatonin (MEL) from a stepchild of hormone research to a best-seller of drug marketing. Melatonin, the hormone of the pineal gland, provides temporal information on diurnal and seasonal variation to the body and brain and it is involved in the synchronization of many different aspects of circadian systems to the light-dark cycle. In addition to these receptor-mediated functions, MEL may act as a modulator of intracellular signal transduction to enhance or suppress the responses of many different cells to other incoming signals. Melatonin is also a potent scavenger of reactive oxygen species and may thus protect cells and tissues against radical-mediated damages. The production of MEL declines with increasing age, and circulating MEL levels are affected by certain pharmacological or physiological manipulations. Animal and cell culture experiments suggest that MEL may have beneficial effects on certain aspects of aging and age-associated diseases. Of particular interest in this respect are reports on the influence of MEL on the brain and the immune system. The sole sufficiently investigated indication in humans is the treatment of certain sleep disorders from the group of sleep-wake-rhythm disturbances. These manifest themselves by sleep time of the day, i.e. in shift workers, after flights across time zones and in some aged persons. Clinical studies need to be performed in order to identify possible side effects of long-term MEL treatment. Serious concerns are raised about the use of uncontrolled, impure, or partially degraded MEL preparations.     

Melatonin hype hard to swallow

Melatonin is being touted as the latest cure-all. But in their eagerness to explain to the public the possible health benefits of this natural hormone, the mass media as well as some scientists have misrepresented the scientific data.     

Melatonin rhythm in human milk

The pineal hormone melatonin exhibits a circadian rhythm in body fluids. No data are available on melatonin in human milk. The present study was undertaken to determine whether melatonin is detectable in human milk and, if so, whether it exhibits a daily rhythm. Blood and milk were sampled between 1400-1700 h and again between 0200-0400 h from 10 mothers 3-4 days after delivery. Melatonin in both fluids was beyond the limit of detection during the day, whereas during the night, its concentration was 280 +/- 34 pmol/L in serum and 99 +/- 26 pmol/L in milk. Six mothers collected milk after each feeding throughout 1 24-h period within 3 months after delivery. Melatonin in the milk of all subjects exhibited a pronounced daily rhythm, with high levels during the night and undetectable levels during the day. The presence of the rhythm in milk suggests that melatonin fluctuations in milk might communicate time of day information to breast-fed infants.     

Melatonin: a sleep-promoting hormone

This review discusses the issue of a dual effect of melatonin on sleep: acute sleep promotion that typically occurs within one hour of administration, and the ability to alter the phase of an underlying circadian pacemaker after a repeated melatonin treatment. The authors suggest that both mechanisms are at work, that they are complementary, and that they may manifest jointly or separately. The review provides some basic information on melatonin, an overview of the literature, and the authors' experience in studying the acute effects of melatonin treatment in humans of different age groups. This review also illustrates the authors' cautious attitude toward melatonin treatment that induces supraphysiologic circulating levels of the hormone.     

Childhood depression, stressors and parental depression

The relationship between depression and stressors and the relationship between depression in children and depression in their parents were investigated. Depressed children aged 7-11 years (n = 20) were compared with clinical non-depressed children (n = 88) and normal children (n = 55). Children, mothers and fathers in the three groups were tested. Measures included the Children's Depression Inventory, Recent Life Events Scale, Stressor Scale and Beck Depression Inventory. The findings showed that children and mothers in the depressed group reported more stressors than other children and other mothers while fathers of children in the depressed group did not report more stressors. The findings also showed that mothers of depressed children were more depressed than mothers of normal children while there were no differences between the scores of fathers in the three groups.     

Melatonin. Physiology, pathophysiology and possible therapeutic approaches

Patients presenting with the major brain arteries (MBA) pathologies were examined by a novel diagnostic tool relying on prolonged latent evoked potentials in response to rotating stimulation (EPR), which allowed an objective quantitative assessment to be performed of central vestibular dysfunction. This approach in the form of a computer programme permitted the testing of patients presenting with MBA pathologies during the preclinical stage of the condition, prior to carrying out such complicated surgical studies as angiography. The EPS method is simple, cost-effective, and convenient in screening examinations, enabling the brain vascular pathology to be detected during the stage of early functional disorders.     

Dopamine and depression

The dopamine hypothesis of schizophrenia and the emphasis on other neurotransmitters, most notably norepinephrine, serotonin, and acetylcholine, in the pathogenesis of depression, have focused attention away from substantial evidence implicating dopamine in affective disorders. The clinical evidence includes alterations in depressive symptoms with aging (concomitant with possible changes in dopamine metabolism), potential dopaminergic involvement in several subtypes of depression, similarities between some of the symptoms of Parkinson's disease and those of depression (including psychomotor retardation and diminished motivation), and potential dopaminergic abnormalities in seasonal mood disorder. The biochemical evidence in patients with depression derives from studies of homovanillic acid, a dopamine metabolite, indicating diminished dopamine turnover. In addition, there is a considerable amount of pharmacologic evidence regarding the efficacy of antidepressants with dopaminergic effects in the treatment of depression. We conclude that dopamine likely contributes significantly to the pathophysiology of depression. However, the role of dopamine in this syndrome must be understood in the context of existing theories involving other neurotransmitters which may act independently, and interact with dopamine and other neurochemicals, to contribute to depression.     

Cognition and depression

OBJECTIVES: To find the relationship between cognitive deterioration and the symptoms of depression. PATIENTS AND METHODS: A sample from the community of 602 persons, 200 of whom had been diagnosed as having dementia and 81 depression. Cognitive deterioration was evaluated using the CAMLOG and the depressive symptoms by means of the CAMDEX depression scale. RESULTS: On multiple regression analysis it was observed that the CAMLOG did not influence the results on the depression scale. Similarly, on ANOVA it was seen that the diagnosis of depression did not influence the results of CAMLOG either. CONCLUSIONS: Cognitive deterioration does not affect depressive symptoms, nor does depression affect cognitive function.     

Melatonin treatment for circadian rhythm sleep disorders

We administered 1-3 mg melatonin to 11 patients (eight men, three women, aged 16-46 years) with circadian rhythm sleep disorders; nine with delayed sleep phase syndrome and two with non-24-hour sleep-wake syndrome. Sleep logs were recorded throughout the study periods and actigraph and rectal temperature were monitored during treatment periods. Melatonin was administered 1-2 h before the desirable bedtime for expected phase-shifting, or 0.5-1 h before habitual bedtime for gradual advance expecting an hypnotic effect of the melatonin. Melatonin treatments were successful in 6/11 patients. Timing and dose of melatonin administration, together with its pharmacological properties for circadian rhythm sleep disorders, should be further studied.     

Melatonin and delayed sleep phase syndrome: ambulatory polygraphic evaluation

The present study objectively evaluated the efficacy of oral 5 mg day-1 melatonin in advancing the sleep-wake rhythm in patients with delayed sleep phase syndrome (DSPS). Six patients underwent ambulatory sleep monitoring for 72 h before and 48 h after 1 month of melatonin treatment. In each patient melatonin was administered on the basis of his own estimated dim light melatonin onset (DLMO) delay. Mean advances in sleep onset time of 115 min and in final awakening hour of 106 min were found after treatment, with no significant changes in sleep architecture parameters. Our study objectively confirms previous data obtained by a sleep-wake subjective diary on the efficacy of melatonin DSPS.     

Melatonin chimeras alter reproductive development and photorefractoriness in Siberian hamsters

Apoptosis is well accepted as a type of cell death occurring in the development of mammalian muscles, but the death of adult myofibres in neuromuscular disorders and exercise-induced muscle damage is usually explained in terms of muscle necrosis. The current view that apoptosis precedes necrosis in death of dystrophin-deficient muscle fibres of mdx mouse has been well substantiated. Moreover, apoptotic myonuclei have been reported to increase in mdx mice 2 days after spontaneous exercise. To investigate the contribution of apoptosis to exercise-induced damage of normal muscle fibre a time-course analysis has been performed in adult C57BL/6 mice. Groups of five mice were sacrificed immediately after the end of the exercise, and after a rest period of 6 or 96 h. The amount of apoptosis in leg muscles was assessed by electron microscopy, by the terminal deoxynucleotidyl transferase assay and by electrophoretic detection of fragmented DNA; the expression of Bcl-2, Bax, Fas, ICE, p53 and ubiquitin was examined by immunohistochemistry and Western blot. Absent in muscles of normal 'sedentary' mice, apoptotic myonuclei peak in muscles of normal mice after a night of spontaneous wheel-running (4% +/- 3.5, immediately and 2.5% +/- 1.8 after 6 h rest, P < 0.05 vs non-runner mice); they then decrease but are present 4 days later (0.8% +/- 1.5). Satellite cells are also involved in the apoptotic process. Myofibre content of Bcl-2 decreases whereas Bax, Fas, ICE and ubiquitin modify their pattern of expression in correlation with the changes in apoptotic myonuclei. Apoptosis of endothelial cells is present after the night of wheel-running and with a twofold increase 4 days later (1.5 +/- 2.3 and 4.8 +/- 4.4 P < 0.05, respectively). Satellite cells are also involved in the apoptotic process. Thus, spontaneous running in unaccustomed mice increases the number of apoptotic nuclei in adult muscle fibres and in endothelial cells. It remains to be established whether muscle apoptosis is restricted to the repair mechanisms, as often suggested in many pathologic processes, or it is also part of pathogenesis of muscle damage. Regardless of whether these results are extended to human dystrophies, the clinical implications in terms of secondary pathogenetic mechanisms and muscle training are obvious.