Predictors of short-term treatment outcome in bulimia nervosa inpatients.

Recent studies, mostly performed on bulimic outpatients, did not find consistent predictors of treatment outcome in bulimia nervosa. This is the first study to investigate anamnestic and clinical factors predictive of the short-term outcome of hospital treatment in 31 female bulimia nervosa patients with a mean age of 22.9 yr. Treatment outcome was assessed by several self-rating instruments measuring different features of the specific and unspecific psychopathology of bulimia nervosa. The most relevant predictors of the outcome of the 8-week hospital treatment were duration of previous inpatient treatments for bulimia, the intensity of anorexic tendency and the pretreatment level of depression. The majority of predictors tested did not show a strong relationship to treatment outcome. The findings are discussed in relation to results of other studies as well as to possible implications for treatment and research.

Effect of dexfenfluramine on sleep in healthy subjects.

The acute effects of dexfenfluramine on nocturnal sleep were studied in ten healthy male subjects by means of sleep EEG recordings and ratings of subjective sleep quality. Four different dosages (3 mg, 7 mg, 15 mg, and 30 mg) were tested, administered over a period of 3 days each. Under 15 mg and 30 mg dexfenfluramine, only slight effects on sleep were observed: 15 mg led to decreased sleep efficiency in the first night of medication, and to reduced percentage of slow wave sleep in the first and third night. A significant lengthening of REM latency was present in the third night under 30 mg dexfenfluramine, without changes in other REM sleep parameters. Daily doses of 3 mg and 7 mg dexfenfluramine did not influence sleep, except for a significant REM latency reduction observed in the first night under 3 mg. Apart from a transient slight impairment under 30 mg, ratings of subjective sleep quality did not mirror any impact of dexfenfluramine. The data suggest that therapeutic dosages of dexfenfluramine only slightly influence nocturnal sleep, which contrasts with the known impact of other anti-obesity agents like the amphetamines. Unlike classical antidepressants, dexfenfluramine does not reduce REM sleep; in light of a hypothetical link between REM sleep reduction and antidepressant action of a drug, dexfenfluramine is not expected to have a pronounced antidepressant effect.

Visual palatability of food in patients with eating disorders and dieting women.

The effects of 19 meals of different caloric content on slides on palatability and hypothetical duration of consumption were investigated in 7 patients with anorexia nervosa, 17 patients with bulimia nervosa at the beginning and after 8 weeks of hospital treatment. Nine healthy females served as controls. At the beginning of treatment, palatability of low caloric food was significantly higher and hypothetical duration of consumption of high caloric food was significantly longer in patients when compared to controls. After 8 weeks, in the patients palatability of low caloric food had decreased. Dislike for high caloric food remained stable in anorexics.

[Psychological effects of previous treatment experiences with neuroleptics]. / Psychologische Wirkungen von Behandlungsvorerfahrungen mit Neuroleptika.

Stable attitudes towards illness and treatment and a high compliance with a 5-week low dose neuroleptic treatment (with/without anticonvulsant adjuvant therapy) were observed in 18 inpatients with schizophrenic disorders (ICD-9, DSM-III-R). Patients having previously received neuroleptics showed more compliant attitudes and greater satisfaction with the treatment, and complained less often about side effects. Noncompliant attitudes were related to dissatisfaction with treatment and self-rated depressed mood. Results of this pilot study are discussed, considering methodological problems and possible therapeutic implications.

Effects and limitations of cognitive behavior therapy in bulimia inpatients.

Cognitive behavior therapy was applied to 8 inpatients with bulimia (DSM-III). Improvement of bulimia was superior when compared to 6 bulimics treated with nonspecific psychotherapy. Social maladjustment was linked to the maintenance of bulimia. The effectiveness of cognitive behavior therapy seemed to be impaired by co-morbidity and dysphoric mood. Therefore a more structured externally controlled behavioral hospital treatment program is recommended.

Modifications and problems of behavioural inpatient management of anorexia nervosa: a "patient-suited" approach?

Several treatment modalities, especially behaviour therapy, had been successfully administered in order to normalize body weight in anorexia nervosa inpatients. However, improvement in affective, cognitive and psychosocial features and associated psychopathologic symptoms was rather poor. It is hypothesized that the limited effect of behaviour therapy may be also due to therapeutic shortcomings of the behavioural treatment programme. In the present study of 16 anorectic inpatients a behavioural treatment programme, which had been applied in a former investigation at the same unit, was modified and yielded the following results: rapid increase in weight, good improvement of anorectic and depressive symptoms and a treatment duration of less than 3 months. Although the short-term outcome of the modified treatment programme is encouraging, the therapeutic difficulties encountered in this programme deserve special attention and its long-term effects on the course and prognosis of anorexia nervosa have to be established.

Cortisol response to various stressful situations: relationship to personality variables and coping styles.

Studies on personality traits and coping styles as determinants of interindividual differences in neuroendocrine responses to stress have not yet yielded conclusive results. In a previous investigation, strong hints to distinct interindividual differences in the susceptibility of the HPA axis of 12 male volunteers aged 27 +/- 5 years exposed to five different stress situations were found. In the present report, psychometric variables (personality traits and coping styles) assessed in the same subjects before the study were analyzed to test whether specific psychometric variables were related to the interindividual differences in the susceptibility of the HPA axis. The results revealed that interindividual differences in the frequency of cortisol responses to stress situations could not be predicted by any of the psychometric variables investigated. The question if psychological factors contribute to neuroendocrine stress response and to what degree warrants further interest. These preliminary findings suggest, however, that nonpsychological factors should be considered more seriously as determinants of interindividual differences in neuroendocrine stress responses in healthy subjects as well as in psychiatric patients.

Past and present strategies of research on the HPA-axis in psychiatry.

Hypercortisolism in depression has been extensively studied during the last three decades. The main hypothesis regarding origin and clinical relevance of this phenomenon, however, has changed significantly. Up to the mid-seventies hypercortisolism was conceived as consequence of stress modified by the degree of unconscious defense mechanisms in different forms of depressive or non-depressive psychiatric disorders. At the end of the seventies this point of view changed considerably. Hypercortisolism was regarded as a biological statemarker of the endogenous subtype of depression with clinical differential-diagnostic relevance. An abnormal dexamethasone suppression test (DST) was assumed to be the best indication of increased activation of the cortisol system. These conclusions turned out to be wrong. DST results are not specific for melancholia and the test seems to be of limited value for measuring the function of the HPA-axis. Intervening variables, such as weight loss, drug and alcohol withdrawal or situational stress, influence the test results significantly, independent of the nosological classification. Additionally, interindividual differences in the susceptibility of the HPA-axis may decisively influence the the activation of the HPA-axis as well in healthy subjects under stress as in psychiatric patients.

Methodological aspects of hCRF-stimulated ACTH and cortisol secretion in healthy subjects.

This study, aimed at clarifying some methodological problems of the hCRF stimulation test, was performed on 12 healthy male volunteers. ACTH and cortisol increases after 30 min and their maximum increase proved to be highly reliable response parameters for the net area under the response curve of both hormones. An influence of baseline hormone values on the maximum response was apparent for cortisol but not for ACTH. Cortisol, but not ACTH, revealed a stable test-retest reliability. There were no correlations between ACTH and cortisol responses to hCRF.

Interindividual differences in the susceptibility of the cortisol system: an important factor for the degree of hypercortisolism in stress situations?

Whereas in psychophysiological research, the specificity of the individual responses has been assumed to be an important trait variable influencing the investigated parameters in stress experiments or in psychopathological states, in psychoneuroendocrinology, the individual differences in the susceptibility of the investigated neuroendocrine axes have been widely neglected. The present study on the cortisol response of 12 healthy young men to 5 different stress tests is considered to be an initial orientation step into this field. All five stress tests (quiz, arithmetic tasks, stress film, cold pressor test, and physical exercise test) could be proven to be effective stimuli regarding the cortisol system. There was, however, a broad spectrum of cortisol responses among the 12 subjects, with a continuum between complete reactors and nonreactors. This did not correlate with the subjective judgment of stress at all. Although the data showed a tendency toward an augmented dispersion of the response frequencies in comparison with random variation, the limited sample size of subjects and stress tests did not allow a statistically significant proof of a stimulus-independent, individual response specificity. Further experimental clarification seems to be necessary to avoid misinterpretations of neuroendocrine data in psychiatric disorders due to neglect of this variable.

The influence of the muscarinic agonist RS 86 on the cortisol system.

To test the assumption that activation of the hypothalamic-pituitary-adrenocortical (HPA) axis is mediated by cholinergic neurons, the cortisol response to the administration of the muscarinic agonist RS 86 was investigated in 12 healthy volunteers. In addition, prolactin and growth hormone secretion patterns were assessed. No significant increase in plasma cortisol or growth hormone was observed after the administration of 1.5 and 3.0 mg RS 86, respectively. However, there was a slight increase in prolactin serum concentration after 3.0 mg RS 86. As RS 86, when used in the same dose range, causes a shortening of rapid eye movement (REM) latency and displays antimanic properties, it is unlikely that a reduced dosage of RS 86 in itself accounts for the lack of stimulation of the HPA axis. If one assumes that in humans the stimulation of the HPA axis is under cholinergic control, then the failure of RS 86 to increase cortisol might be attributable to the fact that different subtypes of muscarinic neurons, for which RS 86 is not a full agonist, are involved, or else nicotinic neurons are implicated in the activation of the HPA axis.

The nature of neuroendocrine abnormalities in depression: a controversial issue in contemporary psychiatry.

Neuroendocrine abnormalities in depression have been regarded, by many authors, as relatively specific markers of nosological subtypes of the disorder, e.g. primary vs. secondary, endogenous vs. non-endogenous or unipolar vs. bipolar depression. They should reflect the same changes in central neurotransmitters (e.g. noradrenergic insufficiency and/or cholinergic hyperactivity) that were hypothesized as the cause of clinical symptoms. This view is challenged on the basis of our own neuroendocrine investigations in 317 psychiatric patients and 103 normal controls. According to these studies the abnormalities are nosologically rather unspecific. They are induced by a large variety of factors, e.g. emotional stress associated with the clinical symptomatology, weight loss due to malnutrition as a consequence of reduced appetite, medication and drug withdrawal. Stress-induced hypercortisolism appears to be the most common abnormality that may trigger other neuroendocrine dysfunctions, such as a blunted TSH response to TRH. Differences in neuroendocrine abnormalities of depressives are probably due to variations in the manifold factors influencing the hormonal axes involved, to temporal changes in hormonal patterns (e.g. one abnormality triggering another) and to individual differences in the basic activity and the responsiveness of the various axes.

Disturbed cortisol secretion in man: contrasting Cushing's disease and endogenous depression.

A disturbed regulation of cortisol secretion is the principal pathology of Cushing's disease and is also the most widely reported neuroendocrine dysfunction in endogenous depression. Because additional clinical signs in both diseases indicated a hypothetical common pathway, we examined 17 patients suffering from Cushing's disease, following a protocol identical to that used in depressed patients (e.g., Hamilton Rating Scale for Depression, self-rating scales, and a clinical interview). Affective disorders, frequently observed in patients with Cushing's disease, were undetectable after surgical treatment (adrenalectomy or microadenomectomy of hypercortisolism). This was an unexpected result, since we found that recovered patients were still characterized by a disturbance of glucocorticoid feedback regulation, probably acting at the hypothalamic level. Our results, as well as numerous reports from others, failed to support the hypothesis that an impaired regulation of cortisol is directly linked to depressive illness.