The effect of a mental challenge test of plasma norepinephrine and cortisol in bulimia nervosa and in controls.
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Adult↗
Biomedical subjects
K M Pirke
Publications and source records attributed to K M Pirke.
Plasma norepinephrine after a standardized test meal in acute and remitted patients with anorexia nervosa and in healthy controls.
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Adult↗
Activation of 5-HT1C-receptors suppresses excessive wheel running induced by semi-starvation in the rat.
Male Wistar rats were housed in cages linked to running wheels and fed on a schedule designed to reduce their body weight by 20-30%. During this period of semi-starvation the rats increased their daily running wheel activity (RWA) by up to 30 km/day. RWA could be kept at this level provided that body weight was kept constant. Different serotonin receptor (5-HT) agonists and antagonists were tested for their effects on RWA and it was found that RWA could be suppressed only by agonists with high affinity for the 5-HT1C receptor (TFMPP, mCPP, DOI and quipazine). Serotonin receptor agonists, which do not pass the blood-brain barrier, and 5-HT itself had no effect on RWA. The inhibitory effect of the agonists on RWA was prevented by pretreatment with antagonists that also had high affinity for 5-HT1C receptors (mianserin, metergoline and mesulergine). From these results we conclude that semi-starvation-induced hyperactivity can be blocked by 5-HT1C agonists. Furthermore we suggest that the animal model presented in this study might be a useful tool for in vivo studies on selective 5-HT1C receptor activation.
Animals↗
Body size perception and body satisfaction in restrained and unrestrained eaters.
In 21 restrained and 20 unrestrained eaters body size perception was measured using the video distortion technique (VDT), the image marking procedure (IMP) and the kinesthetic size estimating apparatus (KSEA). Body satisfaction was assessed by questionnaires (Body Shape Questionnaire, Dieting scale of the Eating Attitudes Test). Restrained eaters showed no systematic over- or underestimation of the body size but less perceptual accuracy (in VDT and KSEA). Furthermore, they were clearly more dissatisfied with their bodies than unrestrained eaters. Both findings were unrelated to each other. In both groups depressive mood or thoughts seemed to be associated with body dissatisfaction but not with body size misperception. Objective body measures (body mass index, body fat content) were not related to either body size perception or body satisfaction. The findings suggest that a perceptual uncertainty in regard to body size (either for visual or for somatosensory aspects) has already developed in restrained eaters, which may constitute a predisposition for more overt forms of body size misperception as found in eating disorder patients.
Behavior Therapy↗
Activation of alpha 2-adrenoceptors suppresses excessive wheel running in the semistarvation-induced hyperactive rat.
Male Wistar rats were housed in cages linked to running wheels and fed on a schedule designed to reduce their body weight by 20-30%. During this period of semistarvation, rats increased their daily running wheel activity (RWA) by up to 30 km/day. RWA could be kept at this level provided that body weight was kept constant. Different alpha-adrenergic agonists and antagonists were tested for their effects on RWA and it was found that RWA could be suppressed only by agonists that display high affinity for the alpha 2-receptor (clonidine and guanfacine). Neither antagonist had an effect on RWA. Clonidine's inhibiting effect on RWA was prevented by pretreatment with yohimbine, which also has high affinity for alpha 2-receptors. From these results, we conclude that semistarvation-induced hyperactivity can be blocked by alpha 2-agonists. In view of this result and those that were obtained in previous studies, a theoretical model for the development of semistarvation-induced hyperactivity will be presented.
Adrenergic alpha-Agonists↗
Cortisol levels and vigilance in eating disorder patients.
Elevated plasma levels of cortisol, as well as deficits in cognitive processes such as attention, have been observed in patients with eating disorders. The association between plasma cortisol and performance in vigilance task was studied in 17 patients with bulimia nervosa or anorexia nervosa during the acute phase of their eating disorder. In comparison to normal young women, the patients had a significantly lower hit rate in a discrimination task and showed an impaired perceptual sensitivity index. They also displayed significantly longer reaction times to hits, but not to false alarms. Cortisol levels of the patients were significantly higher than those of the normal controls. When patients were divided according to their median cortisol level, the patients with higher levels performed significantly more poorly than did the patients with lower levels. In the total patient sample, cortisol levels showed a significant negative correlation with hit-rate (r = -.54) and a significant positive correlation with reaction time to hits (r = .70). Other clinical characteristics were not related to cognitive performance. These results suggest a possible role of cortisol in the development of attentional deficits in eating disorder patients.
Adult↗
Everyday eating behavior and menstrual function in young women.
OBJECTIVE: To examine the association of different types of everyday eating behavior with disturbances of menstrual function. DESIGN: Prospective cohort study with two groups, low dietary restraint (n = 13) and high dietary restraint (n = 9), identified with the Three-Factor Eating Questionnaire by Stunkard and Messick. SETTING: Research clinic. PARTICIPANTS: Normal volunteers (students and young professionals). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Frequent serum and urine samples for determination of estradiol (E2), progesterone (P), and metabolites. Food and behavioral diaries. RESULTS: Eleven of the 13 women with low dietary restraint had menstrual cycles that fulfilled the following standard criteria: Serum E2 maximum of 440 pmol/L or more, P maximum of 19 nmol/L or more, and luteal phase length of 9 days or more. Only 2 of the 9 women with high dietary restraint had cycles that satisfied these criteria. Of the remaining 7, 1 had an anovulatory cycle and 6 had decreased P concentrations (P less than 0.05) and/or a shortened luteal phase (P less than 0.02). CONCLUSIONS: High cognitive restraint in everyday eating behavior may be a risk factor for the development of menstrual disturbance in young women.
Adult↗
Gonadotropin secretion in bulimia nervosa.
Twenty-two normal weight women with bulimia nervosa (BN) were studied (mean age, 25 +/- 5 yr; body mass index, 20.2 +/- 2.6 kg/m2). Sixteen of them reported menstrual cycles in the range of 21-42 days, and 6 had experienced absence of menstruation for at least 3 months. Twenty-one healthy women with regular menstrual cycles (mean age, 23 +/- 2 yr; body mass index, 20.7 +/- 1.4) served as the control subjects. Frequent morning blood samples for estradiol (E2) and progesterone (P4) determinations were obtained for the duration of 1 menstrual cycle or for 6 weeks in the case of amenorrhea. LH, FSH, cortisol, and insulin secretion were studied on day 3, 4, or 5 after the onset of a menstrual cycle or on a random day in the 6 BN women with amenorrhea. Blood samples were collected at 15-min intervals from 1800-0600 h for LH and FSH and at 30-min intervals from 2400-0600 h for cortisol and insulin. Nineteen of the 21 controls, but only 10 of the 22 BN women, fulfilled the following standard criteria: maximum E2 above 440 pmol/L, maximum P4 above 19 nmol/L, and luteal phase length of 9 days or more. The 10 BN women with normal menstrual cycles had lower mean insulin concentrations than the controls (70 +/- 20 vs. 120 +/- 30 pmol/L; P less than 0.01), but gonadotropin secretion, cortisol, and T3 concentrations were similar. The 8 BN women with amenorrhea or ovulatory dysfunction (maximum E2, less than 440 pmol/L; maximum P4, less than 6 nmol/L) displayed decreased mean LH pulse frequency (2.6 +/- 2.4 vs. 5.7 +/- 2.0 pulses/12 h; P less than 0.01), increased mean cortisol (120 +/- 40 vs. 80 +/- 20 nmol/L; P less than 0.01), decreased mean insulin (90 +/- 40 vs. 120 +/- 30 pmol/L; P less than 0.05), and decreased mean T3 concentrations (1.5 +/- 0.3 vs. 1.8 +/- 0.2 nmol/L; P less than 0.01). The data suggest that BN in normal weight women is associated with an increased rate of ovarian dysfunction; decreased pulsatile LH secretion seems to be an important mechanism. Increased cortisol in the disturbed subgroup indicates that activation of the hypothalamic-pituitary-adrenal axis may play a role in the pathogenesis of gonadal dysfunction in bulimia nervosa.
Adult↗
Average total energy expenditure in anorexia nervosa, bulimia nervosa, and healthy young women.
The double-labeled water method was used to measure average daily total energy expenditure (EE) in 11 healthy normal-weight women classified as unrestrained eaters, in 8 patients with anorexia nervosa, and in 8 patients with bulimia nervosa. The body mass index was 20.0 +/- 1.3 kg/m2 in the control group, 15.2 +/- 5.6 kg/m2 in the anorectic groups, and 19.7 +/- 1.9 kg/m2 in the bulimic group. EE was measured over a 2-week period during which weight remained constant in all groups and was 2357 +/- 504 kcal/day for the controls, 2510 +/- 920 kcal/day for the bulimics, and 2899 +/- 656 kcal/day for the anorectics. Differences were not significant among groups. Physical activity was recorded in diaries by all subjects. Anorectic patients showed significantly more activity than all other groups. The data suggest that EE is high in anorectic patients as a consequence of physical activity.
Adult↗
Pain sensitivity in anorexia nervosa and bulimia nervosa.
Pain threshold was measured with short heat stimuli using a contact thermode in 19 patients with anorexia nervosa, 20 patients with bulimia nervosa, and 21 control subjects. Both patient groups had significantly elevated pain thresholds compared with the control subjects. In the total sample, no substantial covariation could be demonstrated among pain threshold and clinical, physiological, metabolic, or psychological data. However, in separate regression analyses pain threshold correlated significantly (negatively) with local skin temperature in the anorectic patients and almost significantly (positively) with body weight in the bulimic patients. This finding suggests that the reduced pain sensitivity in the two kinds of eating disorders might have different causes.
Adult↗
Assessment of somatosensory indicators of polyneuropathy in patients with eating disorders.
The somatosensory functions of small-diameter nerve fibres were tested on the lower and upper extremities in nine patients with anorexia nervosa, ten patients with bulimia nervosa and ten control subjects, by analysing warmth, cold, and pain thresholds. To test large-diameter nerve fibres, the vibration threshold was also measured. Both patient groups had markedly elevated pain thresholds compared with the control subjects. In contrast, warmth and cold thresholds were only suggestively elevated while vibration thresholds were not at all increased in the patients. A distal-proximal pattern of somatosensory deficits, suggestive of peripheral polyneuropathy, was not observed. Hence, a peripheral polyneuropathy affecting small or large afferent fibres as a consequence of an eating disorder seems to be a rare event.
Adult↗
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.
Adolescent↗
Glucose metabolism in the caudate nuclei of patients with eating disorders, measured by PET.
Regional cerebral glucose metabolism was measured with 18F-2-fluoro-2-deoxyglucose and positron emission tomography in nine patients with bulimia nervosa and in seven patients with anorexia nervosa. Relative caudate glucose metabolism (caudate glucose metabolism divided by global cerebral glucose metabolism) was significantly higher in anorexia nervosa than in bulimia nervosa, suggesting that caudate hyperactivity is characteristic of the anorexic state. Whether increased caudate function is a consequence of anorexic behaviour or whether it is directly involved in the pathogenesis of anorexia nervosa is an issue still to be clarified.
Adult↗
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.
Adult↗
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.
Adolescent↗
Circadian pattern of large neutral amino acids, glucose, insulin, and food intake in anorexia nervosa and bulimia nervosa.
Insulin, glucose, and large neutral amino acids (LNAA) were studied in 10 patients with anorexia nervosa, 13 patients with bulimia nervosa, and 15 healthy controls. Blood samples were collected at hourly intervals during the day and at two-hour intervals during the night over a 24-hour period. Ad libitum caloric and relative carbohydrate intake was significantly reduced in the anorectic and bulimic patients. Elevated concentrations of beta-hydroxybutyric acid (BHBA) were seen in the bulimic group, and low triiodothyronine (T3) concentrations in the anorectic group. Mean plasma glucose and insulin concentrations were significantly lowered in both groups. The tryptophan (Trp) to LNAA ratio was reduced in anorectic, but not in bulimic patients. These findings suggest that Trp influx into the brain is reduced in anorectic patients, possibly impairing central serotonergic function.
Amino Acids↗
The influence of semistarvation-induced hyperactivity on hypothalamic serotonin metabolism.
Male rats kept in a running wheel developed hyperactivity when food was restricted. Highest activity occurred around noon when food was given. Semistarved sedentary and ad lib fed sedentary and running rats served as controls. Five-hydroxyindole-acetic acid (5-HIAA) in the medial basal hypothalamus was lowest in the sedentary ad lib fed group. Running significantly increased 5-HIAA. Starvation likewise increased 5-HIAA. This effect was further enhanced by hyperactivity. When the circadian rhythm of serotonin (5-HT) and 5-HIAA was studied in the hypothalamus, a minimum of 5-HT as seen in semistarved sedentary and running rats around feeding time (noon). At this time 5-HIAA reached a maximum in the semistarved running rats while semistarved sedentary and ad lib fed rats showed no circadian pattern of 5-HIAA. These data indicate that serotonin turnover in the medial basal hypothalamus is increased as a consequence of semistarvation and hyperactivity.
Animals↗
Dieting and pain sensitivity: a validation of clinical findings.
To validate findings of a reduced pain sensitivity in anorexia and bulimia nervosa, the effects of dieting on somatosensation (especially pain sensitivity) were investigated in healthy young women. One group of subjects (n = 11) received a calorically reduced balanced diet for 21 days, while the other group (n = 14) continued to eat normally. The fasting state induced in the dieting subjects was comparable to that of eating disorder patients, since the dieters showed a reduction of the body mass index, a decrease in triiodothyronine and an increase in beta-hydroxybutyric acid plasma levels. However, neither the thresholds of pain, warmth, cold and vibration sensitivity nor the peripheral skin temperature changed systematically under the diet. Therefore, the reduced pain sensitivity in eating disorder patients is apparently not a mere effect of fasting, but a true pathological feature.
3-Hydroxybutyric Acid↗