Seasonality in affective disorders in Switzerland.

OBJECTIVE: To estimate the prevalence of seasonal affective disorder (SAD) and its subsyndromal form (S-SAD) in Switzerland (47 degrees N). METHOD: A representative sample from all three language areas of Switzerland (n = 980) were given a structured telephone interview using the extended Seasonal Pattern Assessment Questionnaire (SPAQ+). A smaller, but also representative sample in the city of Basel filled in the SPAQ+ form as well as undergoing a structured diagnostic interview. RESULTS: In this Swiss sample, 2.2% of the population presented with symptom severity of SAD, 8.9% with S-SAD. In Basel, a much higher prevalence of SAD was found. Seasonal problems occurred more often in patients with the Diagnostic and Statistical Manual (DSM)-III diagnosis of major affective disorders than in those with pure anxiety disorders or no psychiatric diagnosis. CONCLUSION: These estimates for SAD in Switzerland are similar to those found in the Zürich Study, using other methods, and for populations in the UK, with the limitations inherent in retrospective questionnaire studies.

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.

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.

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.

[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.

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).

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.

Early evening melatonin and S-20098 advance circadian phase and nocturnal regulation of core body temperature.

The phase-shifting capacity and thermoregulatory effects of a single oral administration at 18 h of melatonin (5 mg) or S-20098, a melatonin agonist (5 or 100 mg), was investigated in eight healthy young men in a double-blind placebo crossover design. The unmasking conditions of a shortened constant-routine protocol (mini-CR) were used to collect evening phase markers of physiological parameters. In comparison to placebo, all three drug administrations induced an earlier dim-light melatonin onset (DLMO), an earlier increase in distal skin temperature, and an earlier decrease in core body temperature (CBT), heart rate, and proximal skin temperature. This indicates that administration at 18 h of both melatonin and S-20098 (more pronounced with 100 than 5 mg) induced an earlier regulation of the endogenous circadian nocturnal decline in CBT. On the posttreatment day a second mini-CR revealed persistent significantly phase-advanced circadian rhythms as estimated by DLMO, as well as by the midrange crossing time of CBT and heart rate decline. There were no significant differences between the two doses of S-20098. The data suggest that, in addition to immediate thermoregulatory changes, a phase advance of the circadian system had occurred and that the phase advance could still be measured on the posttreatment day.

Melatonin and S-20098 increase REM sleep and wake-up propensity without modifying NREM sleep homeostasis.

The pineal hormone melatonin has been implicated in the circadian regulation of sleep. In a crossover design, we investigated the effect of acute administration of 5 mg melatonin and a melatonin agonist (S-20098, 5 and 100 mg) in healthy young men when given 5 h before bedtime on sleep structure and electroencephalogram (EEG) power density. Each trial comprised a baseline, a treatment, and a posttreatment sleep episode. Relative to the placebo condition, all treatments phase advanced the core body temperature rhythm [Kräuchi, K., C. Cajochen, D. Möri, C. Hetsch, and A. Wirz-Justice. Sleep Res. 24: 526, 1995; and Kräuchi, K., C. Cajochen, D. Möri, and A. Wirz-Justice. Am. J. Physiol. 272 (Regulatory Integrative Comp. Physiol. 41): R1178-1188, 1997]. Rapid eye movement (REM) sleep was increased after both melatonin and S-20098. This increase in REM sleep was most pronounced in the first REM sleep episode. On the posttreatment night after melatonin and S-20098 administration, more wakefulness was present in the latter one-half of the sleep episode. EEG power density between 0.25 and 20 Hz during either non-REM (NREM) or REM sleep did not differ from placebo. Thus a single early evening dose of melatonin or the agonist S-20098 increases REM sleep propensity and advances sleep termination while, at the same time, the EEG in NREM sleep remains unaffected.

Follow-up study of seasonal affective disorder in Switzerland.

Of 39 diagnosed Seasonal Affective Disorder (SAD) patients who were interviewed 2-5 years after participation in a light therapy trial, 10 continued to have recurrent major depressive episodes in winter, and 17 manifested sub-syndromal SAD (2 patients also had recurrent brief depression, seasonal type). 8 patients had recovered, and 4 had shifted in symptomatology. Thus, over a number of years, the clinical diagnosis changed for the better in 64% of the patients, suggesting that SAD is not a prodromal form of a more chronic major affective disorder, and that light therapy (and perhaps also light-oriented behaviour) reduced the incidence and depth of subsequent depressive episodes. Further evidence for this was the large reduction in use of conventional antidepressant drugs (from 17 to 1) during the follow-up period. Diagnosis of SAD was stable and reliable.

'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.

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.

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.

Circadian rhythms and sleep regulation in seasonal affective disorder.

Seasonal affective disorder (SAD) is characterised by recurrent episodes in autumn and winter of depression, hypersomnia, augmented appetite with carbohydrate craving, and weight gain, and can be successfully treated with bright light. Circadian rhythm hypotheses (summarized in) have stimulated research into the pathophysiology of SAD, postulating that: 1.The illness is a consequence of delayed phase position, 2.It is correlated with diminished circadian amplitude, or 3.It results from changes in the nocturnal duration between dusk and dawn e.g. of low core body temperature or melatonin secretion. Light is considered to act directly on the circadian pacemaker ('Process C') and not on sleep dependent processes ('Process S'). Thus successful treatment of SAD must act via mechanisms within known retinohypothalamic pathways. Conversely, emergence of SAD symptoms may reflect inappropriate neurobiological response to decreasing daylength.

Long-term follow-up of depression in seasonal affective disorder.

Twenty-six patients diagnosed as having seasonal affective disorder (SAD) completed weekly depression self-ratings for at least 2.5 and up to 8.25 years. Seasonal recurrence of depression persisted in nine patients, seven remitted, four were chronically depressed, and six showed a diffuse pattern. The age at SAD onset and duration of SAD history before entry into this prospective study could not be identified as predictors of the subsequent course of the disease. Short-lasting, recurrent periods of depression could be identified in many of the long-term records. They were found primarily in autumn and winter in patients with either a persistent seasonal or a remitted pattern. In the core group of patients with persistent seasonal pattern, the onset and offset of depressive periods (DPs) were more variable than the DSM-III-R 60-day window criterion for seasonal pattern allows.

Seasonal affective disorder: are the DSM-III-R criteria valid?

Retrospective analysis of the stringency of diagnosis and therapeutic response was carried out in 80 patients with major recurrent winter depression (SAD) who had participated in controlled light therapy trials in Switzerland from 1984 to 1990. Two groups were formed with respect to anamnestic information: patients whose previous episodes of seasonal depression had been reconstructed graphically, and those who could only globally recollect prior depressive phases. These data were taken to test conformity to DSM-III-R criteria for seasonal pattern, as well as its prognostic usefulness for response to light therapy. The more liberal 'Rosenthal criteria' for SAD of at least two consecutive, seasonally recurring major depressive episodes were sufficient to predict improvement with light: none of the other DSM-III-R criteria differentiated further, and few patients could remember previous depressive episodes in precise detail. Our data support suggestions to revise the restrictive SAD diagnostic criteria for DSM-IV.

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.

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.