Peter Graw

Circadian and wake-dependent modulation of fastest and slowest reaction times during the psychomotor vigilance task

Performance on the psychomotor vigilance task (PVT) sensitively reflects a circadian modulation of neurobehavioral functions, as well as the effect of sleep pressure developing with duration of time awake, without being confounded by a learning curve. Sixteen healthy volunteers underwent two 40-h constant posture protocols in a balanced crossover design. During these protocols, either low sleep pressure conditions were attained by an alternating cycle of 150 min of wakefulness and 75 min of sleep (NAP) protocol, or high sleep pressure conditions were achieved by total sleep deprivation (SD) protocol. During scheduled wakefulness in both protocols, the PVT was carried out every 225 min. Quantitative analysis of the lapses, slowest (90th percentile) and fastest (10th percentile) reaction times (RTs) during the protocols, indicated that the lapses and slowest RTs were sensitive to changes in homeostatic sleep pressure. Our data indicate that the difference between the fastest and slowest RTs (interpercentile range 10th-90th percentile) was particular sensitive to detect very early effects of growing sleep pressure. On the other hand, decrements in PVT performance which were related to circadian phase did not depend significantly on any categorization (such as percentiles of the RTs).

‘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.

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.

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.

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.

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.

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.

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.