Reimer Lund

Circadian rhythms in endogenous depression

A comprehensive study of circadian rhythms was carried out in 16 drug-free patients with endogenous depression, 10 of whom were reinvestigated after clinical remission, and 10 healthy controls. No free-running periods were observed in body temperature, urinary excretion of potassium and free cortisol, or any other variable. Moreover, there was little, if any, indication of phase-advance. The circadian variation of several variables was reduced during depression, e.g., motor activity, body temperature, and (less markedly) urinary potassium, but not cortisol. The circadian worsening of mood tended to occur around the time of awakening during depression, i.e., several hours later than after remission or in normal controls. In patients with circadian variation of self-rated mood, the acrophase of this variable correlated significantly with that of urinary free cortisol. This indicates an entrainment of the disease process to the circadian rhythm of cortisol secretion, probably via circadian variations of neurotransmitters in the hypothalamus. The other circadian phenomena observed in depression can adequately be explained by masking effects (negative or positive) of psychopathological symptoms (e.g., early morning awakening) on overt circadian rhythms.

REM latency in neurotic and endogenous depression and the cholinergic REM induction test

Latency of rapid eye movement (REM) sleep was measured in eight healthy volunteers under baseline conditions and after administration of physostigmine. An infusion of 0.5 mg of physostigmine 5 minutes after sleep onset caused a significant shortening of REM latency in comparison with baseline conditions. In 45 patients with major depression, REM latency during baseline nights was significantly shorter than in control subjects. This shortening of the REM latency was found to be similar in endogenous, neurotic, and unclassified depressed patients. In contrast to findings in the controls, the physostigmine infusion provoked no further significant reduction of REM latency in depressed patients, but awakened the majority of patients. The data concerning spontaneous REM latency and REM latency after physostigmine do not allow a differentiation among the endogenous, neurotic, and unclassified depressed subgroups. The results of the cholinergic REM induction test do not conclusively support the hypothesis of a cholinergic hypersensitivity in depression.

On the origin of early REM episodes in the sleep of depressed patients: a comparison of three hypotheses.

Shortened latency of rapid eye movement (REM) sleep is a feature frequently observed in depressed patients. Three hypotheses on the origin of early REM sleep episodes propose that short REM latency is due to (1) a phase-shift of one subset of the circadian rhythms relative to other circadian rhythms, (2) a loss of inhibition of REM sleep due to a slow wave sleep deficit, or (3) a reduction in amplitude of a putative circadian arousal cycle. From an analysis of experimental data, it is concluded that the hypothesis of a reduced circadian amplitude best explains the early occurrence of REM sleep.

Behavior, attitude, nutrition and endocrinology in anorexia nervosa: A LONGITUDINAL STUDY IN 24 PATIENTS

Twenty‐four anorexia nervosa patients participated in an inpatient broad spectrum behavior therapy program. The changes in body weight, anorectic behaviors and attitudes and endocrine variables (24‐h plasma cortisoml, dexamethasone suppression test, 24‐h plasma luteinizing hormone) were measured. Data indicate that specific anorectic behaviors and attitudes showed significant improvement during inpatient treatment, while attitudes of a more general neurotic scope such as the feeling of insufficiency, general distress, (sexual) anxieties and anancasm did not. On admission 24‐h plasma cortisol levels were elevated, episodic secretory spikes occurred at unusual times and the number was increased, cortisol plasma halflife was increased and non‐suppression of cortisol secretion following the application of dexamethasone was observed. All these parameters normalized already after 10 % weight gain. 24‐h plasma LH pattern showed a close relationship with body weight. Our data suggest that the dysfunctions in anorexia nervosa patients in the hyporthalamo‐pituitary‐adrenal and ‐gonadal axis have little specificity for this disease and are mainly a consequence of nutritional factors and starvation. The relationship between cortisol and LH‐secretion, behavioral and attitudinal variables and weight gain was more complex than previously suggested by others and a positive relationship between the LH secretory pattern and anorectic symptomatology could not be established.

A review of sleep EEG patterns. Part I: A compilation of amended rules for their visual recognition according to Rechtschaffen and Kales

ZusammenfassungFragestellungAus polysomnographischen Labor- und Feldstudien leitete das DLR-Institut für Luft- und Raumfahrtmedizin Kriterien zum Schutz vor nächtlichen Fluglärm für den Flughafen Leipzig/Halle ab, der zu einem Frachtdrehkreuz ausgebaut werden soll. Mit den hier vorgestellten Analysen sollte untersucht werden, ob die prognostizierte dichte Flugabfolge in der Nacht bei Einhaltung der empfohlenen Kriterien zu gravierenden makrostrukturellen Änderungen des schlafes führt oder nicht.MethodikAls Datengrundlage diente eine Feldstudie, in der am Flughafen Köln/Bonn 64 Anwohner polysomnographisch untersucht wurden. Markov-Prozesse wurden für die Modellierung einer achtstündigen Bettzeit verwendet. Es wurde nur zwischen den beiden Zuständen Wach und Schlaf (S1-S4, REM) unterschieden. Übergangswahrscheinlichkeiten zwischen den beiden Zuständen wurden mit logistischen Regressionsmodellen in Abhängigkeit vom aktuellen Zustand, von der in diesem Zustand bereits verbrachten Dauer, von der verstrichenen Schlafzeit und vom Maximalpegel des Fluggeräusches bestimmt. 3 Flugbetriebsszenarien wurden simuliert: Ruhe, Fluglärm vorwiegend am Anfang der Nacht (Modell A) und Fluglärm vorwiegend am Ende der Nacht (Modell E).ErgebnisseBezogen auf eine Bettzeit von 8 Stunden war der Wachanteil im Vergleich zum Ruhemodell (81,1 min) im Modell A um 3,8 min (+4,7%) und im Modell E um 5,9 min (+7,3%) erhöht. Fluglärm am Ende der Nacht führte jedoch zu größeren Schlafstörungen als Fluglärm am Anfang der Nacht, weshalb empfohlen wird, Fluggeräusche in der zweiten Nachthälfte mit einem Malus von 1,4 dB zu belegen.SchlussfolgerungIm Zusammenhang mit Fluglärmwirkungen auf den Schlaf erlauben Markov-Prozesse die flexible Modellierung abhängiger Ereignisse und unterschiedlicher Betriebsszenarien. Bei einhaltung der vom DLR vorgeschlagenen Schutzkriterien ermitteln die vorgestellten Modelle nur geringfügige fluglärmbedingte Erhöhungen von Wachanteil und der Anzahl zusätzlicher erinnerbarer Aufwachreaktionen.SummaryQuestion of the studyOn the basis of polysomnographic laboratory and field studies, the DLR Institute of Aerospace Medicine has developed a concept to protect against adverse effects of nocturnal aircraft noise at Airport Leipzig/Halle, which will be extended to a freight hub. We investigated whether or not the expected high traffic densities during the night will relevantly interfere with sleep macrostructure, if the criteria suggested by DLR are met.MethodsModels were based on data sampled in a polysomnographic field study on 64 residents living in the vicinity of Airport Cologne/Bonn. Markov processes wer used to model a time in bed (TIB) of 8 h. Only two states were differentiated: wake and sleep, the latter consisting of S1-S4 and REM. Transition probabilities were estimated with logistic regression including current state (wake/sleep), duration of current state, elapsed sleep time, and maximum sound pressure level (SPL) of the aircraft noise event (ANE) as covariates. Three traffic scenarios were simulated: (i) no noise, (ii) aircraft noise at the beginning of the night (model A), and (iii) aircraft noise at the end of the night (model E).ResultsOn the basis of 8 hours TIB and compared to the scenario without aireraft noise (81.1 min), time spent awake increased by 3.8 min (+4.7%) in model A and by 5.9 min (+7.3%) in model E. However, aircraft noise at the end of the night caused more pronounced changes in sleep structure than aircraft noise at the beginning of the night. Therefore, we propose to levy a malus of 1.4 dB on aircraft noise events occurring in the second half of the night.ConclusionIn the context of noise effects on sleep, Markov processes allow for a flexible modelling of dependent events and variable traffic scenarios. If the criteria of the DLR protection concept are met, the models predict only minor noise-induced changes in time spent awake and in the number of awakenings recalled in the morning.

Diurnal variation of mood and the cortisol rhythm in depression and normal states of mind

SummaryA large scale chronobiological investigation was undertaken in 20 drug-free psychiatric inpatients displaying RDC major depression (endogenous subtype) in comparison to 10 healthy control subjects and 10 of the patients after clinical recovery. A series of measurements was taken 6 times a day and, in 8 of a total of 14 variables, also once a night over a period of 10 to 14 days. The following variables were assessed: mood (three different scales), performance (two tests), motor activity (three measures), salivary flow, urinary excretion of water, sodium, potassium, and free cortisol (UFC), and rectal temperature. A phase chart of the acrophases of the 8 variables with measurements taken during day and night revealed two clusters in the depressives and three in the non-depressed subjects. In the depressives, the acrophases of the mood scales clustered around the time of awakening in the morning, together with the acrophase of UFC, whereas all other acrophases clustered in the afternoon. In the non-depressed subjects, however, the mood scales reached their circadian maxima in the middle of the night around the time when sleep was interrupted to take measurements. All other acrophases corresponded roughly with those found in the depressives. The coincidence of the time course of depressed mood and cortisol excretion in the patients was interpreted as reflecting a temporal relationship between diurnal mood swings in depression and the cortisol rhythm. This interpretation was supported by the significant correlation between the acrophases of the two respective rhythms in patients showing a significant diurnal variation in mood. The mood curves of non-depressed subjects seemed unrelated to the cortisol rhythm. Probably, they mirror diurnal fluctuations of vigilance rather than fluctuations of mood. According to the literature, this rhythm is temporally related to the rhythm of melatonin secretion.

The measurement of change in sleep during depression and remission

SummarySleep disturbances, which are a prominent symptom of depressive illness, were analyzed in endogenously depressed patients during depression and during full remission. These disturbances may be described at the level of sleep stages, at the level of the sleep profile, and at the level of consecutive sleep records.The scoring of sleep stages in sleep records of depressive patients provides difficulties, because the temporal coherence of different electrophysiological descriptors of sleep is weakened during depression. The sleep profile of depressed patients is characterized by alterations in the normal sequence of sleep stages and frequent stage changes. The disturbances in the sleep profile are unstable in that they show marked day to day fluctuations. It could be shown in some patients that there is a correlation between parameters of the first REM sleep phase and urinary free cortisol excretion in corresponding nights.

48-Hour-Cycles of Depression and their Biological Concomitants with and without ‘Zeitgebers’. A Case Report

Publisher Summary This chapter describes the 48-hour cycles of depression and their biological concomitants with and without zeitgebers. A general feature of 48-hour cycles in the mental state is that mainly, though not exclusively, general activity and mood are involved with a dramatic change from either one abnormal extreme to the opposite extreme or from one of them to a normal state. Commonly, one state lasts for 24 h so that in the latter case, bad days and good days run in alternation. In most cases, the change takes place during the night while the patients are sleeping so that they awake in the morning with quite a different mental condition compared to the day before. The time of change may vary between patients, but for each individual, this time may be remarkably stable. Very often, the change occurs very rapidly, in some instances even within a few seconds. The transition involves a whole spectrum of symptoms in the areas of activity, mood, thought content, and others. The resulting syndromes cannot be differentiated from those seen in other organic or functional mental disorders, either general paralysis with excitement and/or affective symptomatology or episodic psychoses of a schizophrenic, schizoaffective, or purely affective type.

Vegetative Funktionen und körperliche Aktivität in der endogenen Depression

SummaryVegetative functions were studied in a 66-year-old male patient with 48-h unipolar cycles of depression. Salivary secretion, body temperature, and motor activity were measured at 3-h-intervals during the day and once at night. The mood state was assessed by two self-rating scales. There was a regular alternation between ‘good’ and ‘bad’ days. Salivary secretion was higher on good days, especially in the morning (P<0.002,10:00). The shape of the 24-h-profile was different on good and bad days, with a maximum at 10:00 on good at 16:00 on bad days. The minimum in the night was the same on both good and had days. Body temperature was increased, as compared with normal subjects (mean 37.2° C) and the diurnal variation was slight. On good days, body temperature during the day was about 0.1° C higher than on bad days. Motor activity (arm and leg), registrated by means of the ‘activity watch’, was higher (during the day) on good days. The present data give some hints for a central dysregulation of vegetative functions in endogenous depression.ZusammenfassungBei einem 66 Jahre alten männlichen Patienten mit 48-h-Zyklen einer unipolaren endogenen Depression wurden vegetative Funktionen untersucht. Speichelsekretion, Körpertemperatur und körperliche Aktivität wurden am Tage in 3-h-Abständen und einmal nachts gemessen. Die Stimmung wurde mit Hilfe von zwei Selbstbeurteilungsskalen beurteilt. Die Skalenwerte ergaben eine regelmäßige Abfolge von „guten“ und „schlechten“ Tagen. Die Speichelsekretion war an „guten“ Tagen gegenüber den Meß-werten an „schlechten“ Tagen erhöht. Dieser Unterschied war am Morgen besonders deutlich (P<0.002, 10.00). Die Form des 24-h-Profils der Speichelsekretion war an „guten“ und „schlechten“ Tagen unterschiedlich: an „guten“ Tagen lag das Maximum um 10.00 Uhr, an „schlechten“ Tagen um 16.00 Uhr. Dagegen zeigte die Lage des nächtlichen Minimums keinen Unterschied zwischen „guten“ und „schlechten“ Tagen. Die Meßwerte der Körpertemperatur waren gegenüber Normalwerten deutlich erhöht (Mittelwerte um 37,2° C) und zeigten eine geringe Amplitude des Tagesganges. An „guten“ Tagen lag die Körpertemperatur tagsüber im Mittel um 0,1°C höher als an „schlechten“ Tagen. Die körperliche Aktivität (Arm und Bein) wurde mit Hilfe eines Aktometers („activity watch“) registriert. Die Meßwerte waren tagsüber an „guten“ Tagen höher als an „schlechten“ Tagen. Die vorliegenden Befunde geben Hinweise auf eine zentrale Regulationsstörung vegetativer Funktionen bei der endogenen Depression.

The Origin of Early REM Sleep Episodes in Depression and other Conditions

Normal sleep onset in the human adult is characterized by a transition from wakefulness to non-REM sleep. There is a progression of the sleep stages 1 — 2 — 3 — 4, which is ended after about an hour by the emergence of the first REM sleep episode. Numerous studies have shown that this basic structure of the first sleep cycle is significantly altered in many nights of depressed patients. As Kupfer and coworkers have shown, REM latency is abbreviated during depression (Kupfer, 1976). In addition, the amount of slow wave sleep stages 3 and 4 may be reduced by the illness (Gillin et al., 1979). While a reduction of slow wave sleep has also been observed in other patient samples and in healthy subjects of advanced age, short REM latency has been claimed to be more specific and to represent a biological marker of primary depression (Kupfer, 1976). However, specificity of short REM latency as a marker for depression has been challenged by the fact that short REM sleep latencies may also occur in normal aged subjects (Spiegel, 1981) and in patients with different psychiatric diseases (Jus et al., 1973; Insel et al., 1982). In addition, sleep onset REM episodes (SOREM, latency ≦ 20 minutes after sleep onset) have been observed after a shift of the regular sleep time (Decoster and Foret, 1979), after a reduction of sleep time (Mullaney et al., 1977), in nap studies (Karacan et al., 1970), and in subjects living on an ultradian rest-activity schedule (Weitzman et al., 1974).