Light therapy in seasonal affective disorder is independent of time of day or circadian phase.

OBJECTIVE: We tested the hypothesis that phase-delayed circadian rhythms underlie seasonal affective disorder (SAD) by measuring phase position of 6-sulfatoxymelatonin excretion and comparing antidepressant response to morning or evening light given as a first treatment. DESIGN: Randomized controlled trial. SETTING: Ambulatory. PATIENTS: Thirty-two women and seven men with SAD. INTERVENTION: Light therapy (2500 lux for 1 hour for 1 week) was administered either at 7 AM or 10 PM, preceded by a baseline week and followed by a withdrawal week. RESULTS: Our SAD patient sample was moderately depressed (Hamilton Depression Scale [HAM-D] score 18); a HAM-D reduction of 50% or more was found in 12 of 18 patients given morning and in 15 of 21 patients given evening light (70% response rate). Response was not dependent on age, gender, stage of the menstrual cycle, time of year, or on the timing or duration of sleep. Urinary 6-sulfatoxymelatonin was measured in 30 patients; 22 had phase-delayed circadian rhythms. However, phase position was correlated neither with depth of depression nor with a preferential response to morning or evening light. COMMENT: Both morning and evening light therapy improved depressive symptoms in patients with SAD independent of their circadian phase or sleep timing. These findings argue against a circadian phase-delay hypothesis of the pathophysiology of SAD, or the necessity of a phase-advance by morning light for clinical efficacy. They additionally suggest more practicable and flexible schedules for light therapy in SAD, since time of day is not crucial.

EEG and subjective sleepiness during extended wakefulness in seasonal affective disorder: circadian and homeostatic influences.

BACKGROUND: Seasonal affective disorder (SAD) may reflect a disturbance of circadian phase relationships or a disturbance of sleep-wake dependent processes, both of which change daytime energy and sleepiness levels. METHODS: Under the unmasking conditions of a 40-hour constant routine protocol (CR), self-rated sleepiness and waking electroencephalogram (EEG) power density were assessed in women with SAD (n = 8) and in age-matched healthy control subjects (n = 9). RESULTS: There was no significant effect of season or light treatment in any of the measures. The time course of subjective sleepiness was characterized by a circadian modulation and an overall increase during extended wakefulness in both SAD patients and control subjects. A prominent circadian rhythm of subjective sleepiness was not different in SAD patients and control subjects; however, the progressive buildup of sleepiness, as quantified by nonlinear regression analysis, was significantly reduced in SAD patients, mainly because they were sleepier than control subjects during the first 12 hours of the CR. The time course of waking EEG theta-alpha activity showed a more rapid increase during the first 10 hours of the CR in SAD patients. In contrast to control subjects who showed a progressive increase in the course of the 40-hour episode of extended wakefulness, EEG theta-alpha activity in SAD patients did not further increase over the remainder of the CR. CONCLUSIONS: The data suggest that SAD patients may have a trait (rather than state) deficiency in the homeostatic buildup of sleep pressure during extended wakefulness as indexed by subjective sleepiness and EEG theta-alpha activity.

Power density in theta/alpha frequencies of the waking EEG progressively increases during sustained wakefulness.

Electroencephalogram (EEG) power density and self-rated fatigue were assessed in nine healthy women during a 40-hour period of sustained wakefulness under constant behavioral and environmental conditions (constant routine protocol). Waking EEG recordings were performed for 4 minutes after 3, 10, 27 and 34 hours of prior wakefulness. EEG power density in the 6.25- to 9.0-Hz frequency range progressively increased across the four recordings, suggesting an endogenous homeostatic component in the regulation of the theta/alpha frequencies under constant conditions. Subjective fatigue also exhibited an increasing component in the course of the constant routine protocol, with a clear circadian modulation. Fatigue ratings and the theta/ alpha power density of the waking EEG recorded at the same four time points during the constant routine protocol correlated significantly. Our data demonstrate the presence of a homeostatic component in the control of EEG power density in the 6.25- to 9.0-Hz range.

Morning or night-time melatonin is ineffective in seasonal affective disorder.

Melatonin, at the same doses used to treat circadian-rhythm related sleep disturbances, had no effect on the depressive symptoms in seasonal affective disorder (SAD) patients, whether given early (7 a.m.) or late (11 p.m.) for a week. Slight improvements in sleep were seen with nighttime administration. The circadian rhythmicity of urinary 6-sulphatoxymelatonin was not modified in any way. Melatonin at this dosage (5 mg/day) or at these two times is therefore not a potential alternative treatment for SAD; light remains the therapy of choice.

Early morning melatonin administration impairs psychomotor vigilance.

The acute soporific effect of melatonin in humans has been demonstrated in a range of studies. How alertness and performance are changed after melatonin given in the morning is not yet known. In a double-blind, placebo-controlled study of nine healthy young men, melatonin was given at 0700 h under controlled conditions of a modified constant routine protocol lasting 56 h (2 days, 3 nights with sleep). A clear decrement in neurobehavioral functions as measured by the Psychomotor Vigilance Test lasted for 6 h after melatonin administration (particularly in the lapse domain and median of the reaction time) without any effect on a letter cancellation task. A subjective soporific effect was present but less pronounced. Thus, melatonin taken in the morning requires caution in situations where high attention is needed.

Daytime melatonin administration enhances sleepiness and theta/alpha activity in the waking EEG.

It is still controversial whether the pineal hormone melatonin can be characterized as a hypnotic. We therefore measured subjective sleepiness and waking EEG power density in the range of 0.25-20 Hz after a single dose of melatonin (5 mg). During an 8 h mini-constant routine protocol, melatonin administered in a double blind cross-over design to healthy young men at 1300 h or 1800 h increased subjective sleepiness, as rated half-hourly on three different scales (Visual Analogue Scale, Akerstedt Sleepiness Symptoms Check List, Akerstedt Sleepiness Scale) and objective fatigue as evidenced by augmented waking EEG power density in the theta/alpha range (5.25-9 Hz). The increase in subjective sleepiness reached significance 40 min and 90 min after melatonin administration (at 1300 h and 1800 h, respectively) and lasted for 3 h (at 1300 h) and 5 h (at 1800 h). The increase in the theta/alpha frequencies of the waking EEG occurred immediately after melatonin ingestion and stayed significantly higher parallel to the higher sleepiness ratings. However, the EEG changes appeared before the subjective symptoms of sleepiness became manifest. There was a significant correlation between salivary melatonin levels and the timing of increased subjective sleepiness. Melatonin had no effects on mood.

The relationship of affective state to dietary preference: winter depression and light therapy as a model.

Seasonal affective disorder (SAD) patients often crave carbohydrates when depressed during the winter. We measured dietary intake using a daily Food/Drink Frequency Questionnaire in 36 SAD patients over four conditions: when depressed in winter, during light therapy (1 h 2500 lux, morning or evening), during withdrawal, and when euthymic in summer. Carbohydrate intake (both sweet and starch) in the second half of the day was elevated during winter depression and was as low after light therapy as in summer. The medial hypothalamus is hypothesised to play a key role in coupling 'mood and food' in SAD.

Sleep deprivation response in seasonal affective disorder during a 40-h constant routine.

BACKGROUND: There are no controlled studies investigating the response of patients with seasonal affective disorder (SAD) to a total sleep deprivation (SD). METHODS: The clinical response to SD of patients with SAD in winter was investigated under the stringently controlled conditions of a 40-h constant routine protocol. RESULTS: 52% of the SAD patients (N=11 women) improved, using a mean of a multiple ratings. This is in the range of response found for non-seasonal major depression. In contrast, controls (N=8 women) showed less improvement of mood (29%). CONCLUSION: SAD patients respond to SD as do non-seasonal major depressives. The best discrimination of response was obtained in an observer rating (Clinical Global Impression: global severity improvement), and the morning values of two different self ratings (v. Zerssen depression scale, 100 mm VAS with the criterion of > or =10 mm improvement). LIMITATION: A more reliable estimate of the SD response rate in SAD patients would require a larger group. CLINICAL RELEVANCE: SAD patients do not differ from other subgroups of major depression in their response to SD, and therefore this is an additional treatment option to light therapy.

Winter and summer outdoor light exposure in women with and without seasonal affective disorder.

BACKGROUND: The annual decrease of daylight duration initiates a depressive phase in patients with seasonal affective disorder (SAD), and light therapy treats it. How much bright light exposure in winter and summer these patients actually receive may help understand the pathogenetic factors initiating SAD. METHODS: During a week in winter and summer, women with and without SAD kept daily logs of the time spent outdoors, subjective sleep, and self-ratings of mood and alertness. RESULTS: Compared with the winter depressive state, mood, alertness, and sleep of SAD patients improved in summer to control values, but did not correlate with the amount of light exposure. In summer, patients with SAD spent more time outdoors than controls. LIMITATION: Light logs--in comparison with light monitor measurements--may overestimate light exposure outdoors. CONCLUSION: Women with SAD do not spend less time outdoors in winter than controls, but spend more time outdoors in summer. CLINICAL RELEVANCE: Patients with SAD show a high amplitude seasonal difference in outdoor light exposure. The susceptibility to winter depression may arise not from behaviourally-related lack of sufficient light exposure, but an increased vulnerability to the amount of light received. They may require more light than controls to remain euthymic (higher light exposure in summer, light therapy in winter).

'Natural' light treatment of seasonal affective disorder.

Patients with seasonal affective disorder (SAD) were treated for 1 week either with a daily 1-h morning walk outdoors (natural light) or low-dose artificial light (0.5 h@2800 lux). The latter treatment (given under double-blind conditions) can be considered mainly placebo and did not improve any of the depression self-ratings, whereas natural light exposure improved all self-ratings. According to the Hamilton depression score, 25% remitted after low-dose artificial light and 50% after the walk. Sleep duration or timing were not crucial for the therapeutic response. The morning walk phase-advanced the onset and/or offset of salivary melatonin secretion, but individual clinical improvement could not be correlated with specific phase-shifts. Morning cortisol was decreased. Low-dose artificial light did not modify melatonin or cortisol patterns. This is the first study to provide evidence for the use of outdoor light exposure as a potential alternative or adjuvant to conventional artificial light therapy in SAD.

High intake of sweets late in the day predicts a rapid and persistent response to light therapy in winter depression.

Demographic characteristics, depression ratings, and detailed daily records of symptoms were examined as possible predictors of the response to light therapy of 51 patients with seasonal affective disorder. Of 26 items, high intake (> 1 portion) of sweets in the second half of the day was the best predictor of a rapid and persistent response to light therapy. The intake of sweets may either act on similar neurochemical substrates to those affected by light or provide a behavioral marker for individuals susceptible to light response.

Diurnal variation of symptoms in seasonal affective disorder.

The classic melancholic pattern of depressive symptoms being worse in the morning was present in 3/4 of a sample of 47 seasonal affective disorder patients (SAD), as assessed by global ratings and self-ratings of diurnal variation (DV). The type of DV did not predict response to light, but it did predict relapse within a week: Only those SAD patients with symptoms worse in the evening or no DV did so.

An underlying circannual rhythm in seasonal affective disorder?

A patient diagnosed with seasonal affective disorder (SAD) carried out prospective ratings of depression weekly for nearly a decade. A winter peak of depression and benzodiazepine intake was documented. However, over the years, the depressive episodes shifted toward spring in an apparent free-running circannual rhythm (periodogram peaks at 53 and 55 weeks). This patient may have an underlying seasonal propensity to depression no longer precisely entrained to environmental cues.

[Developmental course of opiate-dependent patients over 6 years (1979-1985)]. / Entwicklungsverläufe Opiatabhängiger über 6 Jahre (1979-1985).

Drug addicts of the Basle area have been analysed during 6 years in connexion with the National Research Programme 'social integration' and also a following project. The results are contradictory to the pessimism which exists against changes of development of drug addicts.

[Phototherapy]. / Lichttherapie.

Recommendations for a light therapy--PREVALENCE OF SEASONAL AFFECTIVE DISORDER (SAD): Ca. 2% of the adult population in Europe; female to male ratio 4:1. DIAGNOSIS: Recurrent major depressive episodes in winter with full remission in summer. DURATION OF LIGHT THERAPY: For 10,000 lux light boxes 30 minutes/day, for 2500 lux light boxes 1-2 hours/day. TIME OF DAY: If possible in the morning after awakening, otherwise at a time of day when a regular daily light therapy is practicable. ONSET OF LIGHT THERAPY EFFECT: Often already after a week (2-4 weeks treatment produces a stable antidepressant effect). SIDE EFFECTS: Rare, can be avoided by reducing the light dosis. OPHTHALMOLOGICAL RISKS: None under normal conditions. Patients with ocular risk factors (e.g. photosensitizing medications) or preexisting retinal diseases should undergo ophthalmologic examination. LIGHT OR ANTIDEPRESSANT DRUGS: Light therapy is the first line treatment for SAD. For partial or non-response, combination of light with SSRIs is recommended. LIGHT THERAPY MAY BE AN ADJUVANT TREATMENT FOR OTHER PSYCHIATRIC ILLNESSES WITH A SEASONAL TIME COURSE: Bulimia nervosa, obsessive-compulsive disorder, panic disorder; there is some preliminary evidence for usefulness in premenstrual dysphoric disorder and also for non-seasonal major depression.