Peter Doerr

Relationship between weight gain and hypothalamic pituitary adrenal function in patients with anorexia nervosa

Abstract Sixteen patients with anorexia nervosa, aged 13 to 29, were studied after adaption to the hospital for one week when they had 63% (51–77%) of their ideal body weight (IBW). A 24-h secretory profile of plasma Cortisol repeated after initial weight gain of 10% in IBW and on discharge and a dexamethasone suppression test with blood sampling from 9.00 h to 19.00 h repeated at each 10% increase in IBW were ascertained. With one exception all patients had either an insufficient suppression or showed an early escape from suppression after dexamethasone administration. After an increase of only 10% in IBW normal suppressibility of the hypothalamic pituitary unit was seen in all patients except for three who showed a more delayed recovery. The 24-h profile of plasma cortisol was characterized by an increased number of secretory episodes, an increase in the time spent in secretory activity, an elevated 24-h mean level and a prolonged plasma half-life. Highly significant changes were seen after initial weight gain and only slight, non-significant changes after final weight gain. It is concluded that starvation-induced metabolic changes in patients with anorexia nervosa lead to a delayed degradation of cortisol and to a central endocrine dysfunction characterized by an increased secretory activity and an insufficient glucocorticoid feedback. Recovery from all endocrine dysfunctions reported here is rapidly achieved during weight gain of only 10% in IBW.

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.

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.

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.

Neuroendocrine Dysfunction in Subtypes of Depression

As pointed out by G. M. Brown and associates in their contribution to this volume, “neuroendocrine function may provide a means of differentiating various subtypes among the affective disorders, because they may mirror the central activity of biogenic amines in depressed subjects. Different types of neurotransmitter deficit have been postulated in depressive illness. Different underlying abnormalities could lead to syndromes which differ with respect to clinical characteristics, visceral symptomatology, and endocrine abnormalities.” They have listed a series of endocrine abnormalities of depressed patients as described in the literature and added information about their own findings on neuroendocrine effects of lithium (see also Prange and Loosen, this volume; Johnson, 1982; Sachar, 1982; Winokur et al., 1982).

Dexamethasone-induced suppression of the circadian rhythm of plasma testosterone in normal adult males

The aim of the present study was to investigate the dexamethasone-induced interference with the circadian rhythm of plasma testosterone. Normal adult males were treated with dexamethasone (3 mg/6 h) for 24 or 48 h or with a combination of dexamethasone and fluoxymesterone for 48 h. Following suppression of the nocturnal rise in testosterone by administration of dexamethasone, testosterone did not resume a circadian rhythm from day 2 to 3 under continued treatment, while plasma LH increased to about twice the baseline level. When the increase in LH was prevented by administration of fluoxymesterone (1.5mg at 6h intervals from 2200h on day 1 to 0400h on day 3) testosterone again did not show a circadian rhythm. Under treatment with dexamethasone and fluoxymesterone the overall 24 h mean of testosterone from day 2 to 3 was 44.2% of the basal level, which was significantly different from the overall mean under treatment with dexamethasone only (61.3%, n = 10, P < 0.02). Following cessation of the 24 h treatment with dexamethasone, testosterone increased slowly from 58.6% of the baseline level (overall mean from 0800 to 1000h on day 2) to 90.4% on day 4 and did not resume a circadian rhythm until day 4–5. To exclude the possibility that dexamethasone may act by attenuating the Leydig cell response to LH, 10 normal adult males were given i.v. injections of 100 μg GnRH at 1 h intervals from 1400 to 2100h with and without 10 h pretreatment with dexamethasone. Neither the pituitary response to GnRH nor the Leydig cell response to LH was modified. On the basis of these and earlier findings it is concluded that dexamethasone abolishes the circadian rhythm of testosterone by blocking the nocturnal rise. Following cessation of treatment with dexamethasone, testosterone does not resume a circadian rhythm until basal levels are reached 48 h later. This is in contrast to plasma cortisol, where a circadian rhythm reappears much earlier while it is still suppressed.

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.

Relationship between receptor occupancy and stimulation of adenosin-3',5'-monophosphate (cAMP) and progesterone production in isolated rat granulosa cells

Abstract In granulosa cells isolated from preovulatory follicles of PMSG-primed immature rats half-maximum steroidogenic response was seen when 3% of the available LH binding sites were occupied by hCG and maximum response was reached at 15–20% saturation. The response in cAMP was much less sensitive; a detectable response was seen at hCG concentrations which elicited about half-maximum progesterone production. Maximum response in cAMP was reached when more than 50% of the available binding sites were occupied. In the presence of the phosphodiesterase inhibitor IBMX the entire range of the progesterone response curve shifted to lower hCG concentrations indicating a sufficient cAMP level within an intracellular compartment for mediating steroidogenic response. Granulosa cells obviously differ from rat Leydig cells where maximum steroidogenic response is achieved when only 1% of the LH receptors are occupied.

The Role of the Hypothalamus-Pituitary-Adrenocortical System in Depression

An increased activity of the hypothalamus-pituitary-adrenocortical system (HPAS) during episodes of depression has been reported by several investigators since the middle of the 1950s (Bryson and Martin 1954; Board et al. 1957; for review see Mason 1968; Rubin and Mandell 1966). As this phenomenon occurs only in a certain proportion of patients suffering from depression and disappears with clinical recovery (see, e.g., Kathol et al. 1984), it can be regarded as a state marker for some depressions, especially severe psychotic forms of endogenous depression (see Carroll et al. 1980; Rudorfer et al. 1982). Originally, HPAS activation in depression was hypothetically related to nonspecific stress induced by the disorder, e.g., via anxiety, inner tension, or other symptoms that seem to indicate a breakdown of ego defenses. This interpretation was, however, questioned on several grounds and finally rejected by most authorities in the field of psychoneuroendocrinology (e.g., Sachar 1975,1982; Carroll and Mendels 1976; Rubin and Kendler 1977; Rubin and Poland 1984). We will restrict our discussion of the problem to two arguments which we have empirically analyzed to some depth. They are both related to reports in the literature concerning the endogenous subtype of depression (melancholia). In this subtype the hyperactivity of the HPAS was found not only to be more pronounced than in other subtypes of the disorder but also to display melancholia-specific features which cannot be explained as stress phenomena.