R.H. van den Hoofdakker

Changes in daily rhythms of body temperature and activity after a single social defeat in rats

The long-term consequences of social stress on daily rhythms of body temperature and activity in rats were studied by means of radiotelemetry with intraperitoneally implanted transmitters. Rats were subjected to a single social defeat by placing them into the territory of a male conspecific for 1 h. Social defeat caused a sharp subsequent reduction in the amplitude of the daily temperature rhythm, which lasted for at least 4 days. The reduced amplitude was mainly due to higher temperatures during the circadian rest phase, i.e., the light period. Movement activity was less affected, but the decrease in activity during the dark phase after defeat correlated significantly with the temperature increase during the light phase. The stress-induced changes in daily rhythms of body temperature and activity are discussed in terms of their relevance to the role of rhythm-disturbances in the pathogenesis of affective disorders.

Changes in behaviour and body weight following a single or double social defeat in rats.

In a series of experiments, the consequences of a single and double social conflict on various behaviours and body weight in rats were studied. Animals were subjected to social defeat by placing them into the territory of an aggressive male conspecific for one hour, either once, or twice at the same time on two consecutive days. To assess the consequences of social defeat, three experiments were performed with independent groups of rats. In the first experiment, an open field test was performed two days after the last conflict. Locomotor activity was strongly reduced after social defeat. There were no differences between the single and double defeat group. To assess the effects of social defeat on subsequent social behaviour, a second experiment was performed in which experimental animals were confronted with an unfamiliar non-aggressive rat two days after a single or double conflict. Social defeat resulted in a reduction of social contact with the unfamiliar conspecific. There was no difference between the single and double conflict group. In the third experiment, the effects of social conflict on food intake, body weight and saccharine preference were measured. Food intake was not affected after a single conflict, but in the double conflict group food intake was decreased for several days. Body weight gain was decreased after both single and double social defeat. The decrease was stronger in the double conflict group. Water intake and saccharine preference were not significantly affected. This study revealed that social defeat in rats causes pronounced changes in various behaviours and body weight. Different aspects of behaviour are differentially affected by defeat with respect to the magnitude and time course of the changes induced. Moreover, different behavioural parameters are differentially sensitive to repetition of the stressor.

Long-term changes in open field behaviour following a single social defeat in rats can be reversed by sleep deprivation

The long-term consequences of a single social defeat on open field behaviour in rats were studied, with special emphasis on the time course of stress-induced changes. Animals were subjected to social defeat by placing them into the territory of an aggressive male conspecific for 1 h. After the defeat session experimental animals were returned to their home cage and their own room, receiving no further cues from the resident. Other animals serving as controls were placed in a clean and empty cage for 1 h. Five-minute open field tests were performed on days 1, 2, 7, 14, and 28 after defeat, with independent groups of rats. Locomotion of the animals was recorded and analyzed with an automated video system. Social defeat resulted in a strong subsequent reduction in open field activity, which lasted till at least 7 days after the conflict. Differences in total travelled distance were no longer significant 2 weeks after the conflict. The latency for moving to the outer ring of the open field arena after the start of the test was still significantly longer 4 weeks after defeat. The stress-induced reduction in open field locomotion could be reversed by 12-h sleep deprivation during the resting phase, an intervention known to have antidepressant effects in humans. Possible relevance of the present findings with respect to human affective disorders is discussed.

EFFECTS OF SEGANSERIN, A 5-HT2 ANTAGONIST, AND TEMAZEPAM ON HUMAN SLEEP STAGES AND EEG POWER SPECTRA

The effects of seganserin, a specific 5HT2 antagonist, on human sleep were assessed in two experiments and compared to the effects of temazepam and sleep deprivation. During daytime recovery sleep after sleep deprivation, seganserin did not significantly enhance visually scored slow wave sleep (SWS, stages 3 + 4) or the EEG power density in the delta frequencies. Under these conditions temazepam reduced the power density in the delta and theta frequencies. During nighttime sleep after a nap in the evening, seganserin caused an increase in SWS, a reduction in intermittent wakefulness, and an enhancement of the power density in the delta and theta frequencies during non-rapid eye movement (NREM) sleep. Temazepam induced a reduction in the power density in the delta and theta frequencies. It is concluded that the 5HT2 antagonist, seganserin, can induce SWS. However, since the spectral results showed that the changes in the sleep EEG were not identical to those induced by sleep deprivation it seems premature to conclude that 5HT2 receptors are primarily involved in NREM sleep regulation.

The prevalence of seasonal affective disorder in The Netherlands: a prospective and retrospective study of seasonal mood variation in the general population.

BACKGROUND The aim of the present study was to assess the prevalence of seasonal affective disorder (SAD) in The Netherlands. METHODS The subjects (n = 5356), randomly selected from community registers, were given the Seasonal Pattern Assessment Questionnaire and the Centre for Epidemiological Studies Depression Scale over a period of 13 months. The response rate was 52.6%. RESULTS Three percent of the respondents met the criteria for winter SAD, 0.1% for summer SAD. The criteria for subsyndromal SAD, a milder form of SAD, were met by 8.5%, 0.3% of whom showed a summer pattern. Younger women received a diagnosis of SAD more often than men or older women. CONCLUSIONS SAD subjects were significantly more often unemployed or on sick leave than other subjects. Respondents who met winter SAD criteria were significantly more depressed than healthy subjects, in both winter and summer. Finally, month of completion had no influence on the number of subjects meeting the SAD criteria.

Effects of light exposure and sleep displacement on dim light melatonin onset

The purpose of the study was to induce in two different ways, a phase‐angle difference between the circadian pacemaker and the imposed sleep–wake cycle in humans, we intended to: (i) shift the circadian pacemaker by exposure to bright light and keep the timing of the sleep–wake cycle fixed; and (ii) keep the timing of the circadian pacemaker fixed by a constant light–dark cycle and displace sleep. We monitored dim light melatonin onset (DLMO), core body temperature and sleep. DLMO was delayed significantly after 3 days of a 3‐h delayed sleep‐phase when compared with 3 days of sleep at a normal or 3‐h advanced sleep‐phase. The shifts in DLMO were not accompanied by shifts in body temperature, changes in waking‐up time or by a change in the duration of the first rapid eye movement (REM) sleep episode. Three days of light exposure in the morning or evening resulted in shifts in DLMO of similar magnitude, but this was accompanied by shifts in the rhythm of body temperature, changes in waking‐up time and in the duration of the first REM sleep episode. We conclude that the changes observed after light exposure reflect shifts in the circadian pacemaker. In contrast, we propose that the changes observed in DLMO after sleep displacement are not mediated by the circadian pacemaker. These results raise some doubts about the reliability of DLMO as a marker of circadian phase in cases of sleep disturbances. Finally, we initiate a search for changes in sleep that might be responsible for the unexpected effects on DLMO.

Morning and evening light treatment of seasonal affective disorder: response, relapse and prediction

Patients with seasonal affective disorder were randomly assigned to treatment with light in the morning (9.00-12.00 a.m.; n = 16; ML) or evening (6.00-9.00 p.m.; n = 11; EL). An intensive 24-day assessment procedure revealed the same response rates: 57% for ML, 50% for EL. During the rest of the winter season a relatively low relapse rate of 54% was found. No differences between ML and EL were found in the time course of depressed mood or fatigue. A significant negative correlation was found between diurnal variation during baseline and therapeutic response: the larger the diurnal variation the less the response, indicating a potential negative predictive value for this symptom. There were no significant correlations between baseline fatigue or hypersomnia and response.

Prophylactic treatment of seasonal affective disorder (SAD) by using light visors: Bright white or infrared light?

BACKGROUND Thirty-eight patients with SAD participated in a light visor study addressing two questions. 1. Can the development of a depressive episode be prevented by daily exposure to bright light started before symptom onset in early fall and continued throughout the winter? 2. Does the light have to be visible in order to have beneficial effects? METHODS Three groups participated in the study: I (n = 14) received bright white light (2500 lux); II, (n = 15) received infrared light (0.18 lux); III (n = 9, control group) did not receive any light treatment at all. RESULTS Infrared light is just as effective as bright white light. Both are more effective than the control condition. CONCLUSIONS Light visors can be effectively used to prevent the development of SAD. The fact that exposure to infrared light was as effective as exposure to bright white light questions the specific role of visible light in the treatment of SAD.

Prediction of the antidepressant response to total sleep deprivation of depressed patients : longitudinal versus single day assessment of diurnal mood variation

The relationship between diurnal variation of mood and the clinical response to total sleep deprivation (TSD) was investigated in 43 depressed patients. The question asked was whether the propensity to produce diurnal variations of mood or the actual mood course on the day before TSD determines the clinical response to TSD. Patients rated their mood three times daily during an experimental period of 56 days. The frequency as well as the amplitude of daily mood changes were assessed during this period. For each patient six TSDs were scheduled: two after days with a positive mood course, two after a negative mood course, and two after days without a diurnal change of mood. This strategy allowed comparisons of TSD responses within patients. Moreover, longitudinally and retrospectively assessed diurnal variation were compared with each other. It was found that patients vary largely in the occurrence of diurnal variations of mood. The propensity to produce diurnal variations either in terms of frequency or amplitude was positively correlated with the response to TSD. Within patients no differences were found in responses to TSDs applied after days with diurnal variations (positive or negative) or without diurnal variations. A second aim was to get more insight into the mechanism relating diurnal variations of mood and the TSD response. Therefore, the interrelatedness of various measures of diurnal variations, such as amplitudes and frequencies of positive or negative diurnal mood changes, was studied, as well as the relationships of these variables with TSD responses. On the basis of the strong interrelatedness it is suggested that they all reflect the same underlying mechanism, to be symbolized by an oscillator, producing positive daily fluctuations of mood.

Self-rated arousal concurrent with the antidepressant response to total sleep deprivation of patients with a major depressive disorder: a disinhibition hypothesis.

SUMMARY  In view of the opposing theories regarding the arousing or de‐arousing action of total sleep deprivation (TSD) in producing antidepressant effects, 23 patients with a major depressive disorder were deprived of a nights sleep twice weekly for two weeks, and self‐rated their condition 38 times using von Zerssens scale for depression and, concurrently, Thayers Activation Deactivation Adjective Check List (AD ACL). Transient relief of depression after TSD, indicated by eight patients, was mimicked by their AD ACL scores, which revealed the same underlying factors as were found in Thayers studies. TSD appears to be simultaneously arousing (giving more energy) and de‐arousing (leading to less tension), while this response takes place against a background of increased tiredness/sleepiness. It is argued that TSD sets off a psychological disinhibition process on the basis of cerebral fatigue; in particular the prefrontal (orbital?) areas of the cerebral cortex may be implicated, possibly in relation to a dampening down of subcortical arousal systems.