Karl-Martin Pirke

Preliminary evidence for reduced cortisol responsivity to psychological stress in women using oral contraceptive medication

In two studies, saliva cortisol responses to the psychological stress of public speaking and mental arithmetic were investigated in women using oral contraceptives (OC; n = 28) and in control women (n = 29). While no significant differences in baseline levels were observed, altered adrenocortical responses were found in OC users. These women showed significantly attenuated cortisol responses to the experimental stressor in both studies, with peak cortisol levels only slightly elevated above baseline levels. These differences could not be attributed to affective responses as indicated in ratings on visual analogue scales assessing subjective stress responses (Study 2). A comparison between control women and men (n = 19) again revealed the previously reported result of larger cortisol responses to psychological stress in males. We conclude that the use of OC may interfere with the adrenocortical response to psychological stress and should therefore be viewed as an important intervening variable. While it appears that differences at a supra-adrenal site is responsible for the observed cortisol hyporesponsiveness in OC users, the physiological mechanisms remain to be elucidated.

Weight loss causes neuroendocrine disturbances: experimental study in healthy starving subjects

A variety of endocrine dysfunctions have been reported for anorexia nervosa, protein caloric malnutrition, and depression. The effect of reduced caloric intake and weight loss on endocrine functions was assessed in an experiment with five healthy female subjects during an initial baseline phase, a 3-week phase of complete food abstinence, weight gain to the original level, and a final baseline phase. During fasting, disturbances in hypothalamic-pituitary-adrenal function were observed, with elevated plasma cortisol levels, increase in the number of secretory episodes, increase in cortisol plasma half-life, and insufficient suppression following 1.5 mg dexamethasone. While all dexamethasone suppression tests (DSTs) were normal at baseline, 7 of 14 DSTs showed insufficient suppression in the fasting phase. During fasting, basal thyroid-stimulating hormone (TSH) values were lowered and the TSH response to thyrotropin-releasing hormone (TRH) was blunted. The plasma level of growth hormone (GH) over 24 hours was elevated during fasting and administration of the alpha 2-adrenergic receptor agonist clonidine resulted in a subnormal GH response after restoration of original body weight. One of the five subjects showed increased irritability, distress, anxiety, and depression as measured by various psychological scales. The results show that reduced caloric intake, weight loss, or catabolic state have powerful effects on several endocrine systems. The specificity of measures of endocrine disturbances (DST, TRH tests, and clonidine tests) as biological markers for certain types of depression must be questioned, and the metabolic state should be given more consideration in future studies.

Endocrine, metabolic, and cranial computed tomographie findings in anorexia nervosa

Computerized tomographic brain scans were completed in 50 inpatients with anorexia nervosa and were compared with an age- and sex-matched control group. Seventy percent of the anorectic patients displayed enlarged lateral ventricles. There was a close link between ventricular size and low weight, but not between ventricular size and duration of the eating disorder. In addition, sulcal widening was observed more frequently in patients with enlarged ventricles than in patients without these structural changes. After weight gain, a statistically significant decrease in ventricular dilatation could be observed even when mean ventricular size still far exceeded that of the control subjects. The analysis of the endocrine and metabolic parameters, known to be indicators for the process of starvation, revealed a significant inverse correlation between triiodothyronine and ventricular size. Various possible pathogenetic mechanisms for the morphological brain alterations in patients with eating disorders are discussed.

Serotonin transporter gene-linked polymorphic region: Allele distributions in relationship to body weight and in anorexia nervosa

Several lines of evidence implicate a role for the serotonergic system in body weight regulation and eating disorders. The magnitude and duration of postsynaptic responses to serotonin (5-HT) is directed by the transport into and release from the presynaptic neuron. Recently, a common polymorphism of a repetitive element in the region of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) was identified that results in a system of two common alleles. The activity of the 5-HTT, as measured in in vitro assays and in human lymphoblastoid cell lines, is dependent on the respective genotype. We thus hypothesized that this polymorphism is relevant for weight regulation in general and is possibly involved in the etiology of anorexia nervosa (AN). Allele frequencies and genotypes were determined in a total of 385 unrelated obese children, adolescents and adults, 112 underweight subjects and 96 patients with AN. Furthermore, both parents of 98 obese children and adolescents and of 55 patients with AN, respectively, were genotyped, thus allowing to test for both association and linkage. The comparison of allele frequencies between obese and underweight probands provided no evidence for a major role of the 5-HTTLPR in weight regulation. Patients with AN had allele frequencies not significantly different to those observed for obese and underweight individuals.

Starvation-induced hyperactivity in the rat: the role of endocrine and neurotransmitter changes.

Semistarved rats develop high running wheel activity. This running activity induces increased norepinephrine, dopamine, and serotonin turnover in the hypothalamus. Corticosterone in plasma becomes increased while luteinizing hormone and testosterone are suppressed. In female rats cyclic gonadal function is suppressed. Running activity in the semistarved rats can be suppressed specifically by serotonin 1-c-agonists and by alpha 2-adrenoceptor agonists. This animal model is helpful in the understanding of the combined effects of starvation and hyperactivity, which are observed in many patients with anorexia nervosa. The observation of the serotonergic system might help to develop a pharmacological treatment of hyperactivity in anorectic patients.

Mood changes and physical complaints during the normal menstrual cycle in healthy young women.

Significant emotional and physical symptoms have been linked to hormonal changes during the menstrual cycle. A critical evaluation of the available studies questions the commonly held belief in menstrual-cycle-related complaints in the majority of normal women. The present study investigated changes in mood, somatic complaints and vegetative variables during the menstrual cycle in 30 healthy young women. Normal cycle function was evaluated and cycle phases were defined according to endocrine data. For all subjects, blood samples were taken at least three times a week to measure estradiol and progesterone. Daily ratings of psychological variables revealed no significant changes in global mood or depression over the cycle. Somatic complaints such as abdominal pain and breast tenderness were significantly related to the luteal, premenstrual, and menstrual phases. Appetite increased in the periovulatory and premenstrual phases. There was a tendency for sexual interest to be highest in the post-menstrual period. Affect and vegetative variables showed no association with hormone levels but were significantly correlated with subjective stress ratings. We conclude that in most healthy young women, cycle-related hormone fluctuations are not accompanied by marked affective changes. Specific physical complaints, however, do occur, particularly in the luteal, premenstrual, and menstrual phases.

Regional cerebral glucose metabolism in anorexia nervosa measured by positron emission tomography

Regional cerebral glucose metabolism was measured in five female anorectic patients, during the anorectic state and after weight gain, using the fluorodeoxyglucose method and positron emission tomography. In addition, these results were compared with those of 15 young male normals. During the anorectic state, significant caudate hypermetabolism was found bilaterally, unlike the finding in repeat measurements or in male normals. In some other brain structures (temporal cortex, lentiform nucleus, thalamus, and brainstem), significant hypermetabolism was also found during the anorectic state, but these results were not concordant for both sides and in both comparisons. There was no difference between patients after improvement and young male normals.

Differences in food-choice frequencies between restrained and unrestrained eaters

Reported frequency of consumption for certain food items was studied in young normal-weight women, classified into 19 unrestrained and 20 restrained eaters by the Three-Factor Eating Questionnaire of Stunkard & Messick (1985). Neither group differed in the consumption of basic foods and snacks but restrained eaters showed a strong tendency to avoid fat. A large percentage of this group was used to consuming artificial sweeteners and other calorie-reduced foodstuffs. These qualitative alterations in the everyday eating behavior of restrained eaters may be one of the links between dietary restraint and binge eating.

Disturbed cholecystokinin secretion in patients with eating disorders

It has been shown that the gastrointestinal hormone cholecystokinin (CCK) induces satiety and reduces food intake in laboratory animals and humans. In the light of this evidence we studied CCK release in patients suffering from eating disorders. The secretion of CCK into the general circulation was measured in 10 anorectic, in 7 bulimic patients, and in 8 healthy controls before and after a high-caloric liquid testmeal. Baseline CCK values were similar in controls (0.6 +/- 0.2 pmol/l) and bulimics (0.6 +/- 0.1 pmol/l) and were significantly increased in the anorectic group (1.8 +/- 0.4 pmol/l) (p less than or equal to 0.005). After eating peak plasma levels increased to 6.1 +/- 0.9 pmol/l in the anorectic, to 3.8 +/- 0.5 pmol/l in the bulimic and to 2.7 +/- 0.6 pmol/l in the control group. All postprandial CCK values were significantly higher in the anorectic group. The secretion of CCK-8-S, an important peptide in the CCK family, was significantly elevated, too. This disturbed CCK secretion in patients suffering from anorexia nervosa, even if it is a secondary, diet-induced defect, may perpetuate this disorder.

Central and peripheral noradrenalin regulation in eating disorders

Norepinephrine and its metabolites were studied in various body fluids (plasma, urine and cerebrospinal fluid) of patients with anorexia nervosa, bulimia nervosa and healthy young women. The reaction of plasma norepinephrine to different stimuli like orthostatic challenge, test meals, standardized exercise, mental challenge tests etc. were studied. All results indicate a reduced noradrenergic activity in the central and peripheral nervous system of patients with eating disorders. The clinical consequences of these changes are hypotension, bradicardia, hypothermia and depression. Evidence is presented that the reduced activity of the sympathetic nervous system is caused by starvation (anorexia nervosa) or intermittent dieting (bulimia nervosa).