Food intake in Prader-Willi syndrome and controls with obesity after administration of a benzodiazepine receptor agonist.

Benzodiazepine receptor (BZR) agonists, used extensively for their anxiolytic effects, have been shown to increase food intake in many mammalian species. Little information, however, is available on the effects of BZR agonists on feeding behaviors of humans. Food intake was evaluated in a 60-minute free-feeding standardized test after the acute administration of the BZR agonist chlordiazepoxide (CDP, Librium; 5 mg or 20 mg) or placebo. Subjects were 12 individuals with the Prader-Willi syndrome (PWS), a disorder characterized by extreme hyperphagia and morbid obesity, and 11 controls with obesity. PWS subjects showed the characteristic hyperphagia associated with the appetite disorder, consuming more than six times as many sandwiches as controls with obesity. Results revealed no significant effect of either dose of CDP on the food intake of either group. Serum assays revealed that dose-dependent, clinically effective levels of CDP and active metabolites were achieved. These results suggest that acute administration of the BZR agonist CDP, at the therapeutic levels used, may not increase food intake in populations with obesity. However, the chronic effects of CDP on appetite in human populations still need to be explored.

Food preferences in Prader-Willi syndrome, normal weight and obese controls.

OBJECTIVE: The aim of this work was to assess the specific food type (high carbohydrate, high fat, high protein) preference profiles of individuals with Prader-Willi syndrome (PWS), obese controls and normal weight individuals. DESIGN: Subjects tasted a food predominantly high in carbohydrate, a food predominantly high in protein and a food predominantly high in fat over repeated trials and indicated their most preferred, second preferred and least preferred foods. Specific items tested on a given trial were counterbalanced in a block randomized fashion. SUBJECTS: These were 12 individuals with Prader-Willi syndrome, 12 matched obese controls (obese, but otherwise normal) and 14 normal weight subjects. MEASUREMENTS: The basic data were expressed as a proportion of each food type selected as most preferred over the total 27 trials. RESULTS: PWS subjects preferred high carbohydrate foods over high protein foods and high protein foods over high fat foods. These subjects demonstrated a statistically reliable difference in preference for high carbohydrate foods over high fat foods. However, normal weight and obese control subjects demonstrated no difference in food preferences. The only significant between-group comparisons were between PWS subjects and obese controls, with the PWS group showing a significantly greater preference for high carbohydrate foods than obese controls. CONCLUSIONS: The obesity of PWS was shown to have a significant and distinctly different food preference profile from normal weight and obese controls. The differences in food preference between the obese PWS and non-PWS subjects is in accord with the growing recognition of functional subgroups within the obese population, that may have not only differing underlying etiologies, but also distinct behavioral profiles of ingestion.

Illusions, arithmetic, and the bidirectional modulation of vagal control of the heart.

Behavioral contexts can evoke a variety of autonomic modes of response, characterized by reciprocal, coactive, or independent changes in the autonomic divisions. The present study investigated the modes of autonomic response to visual illusion and mental arithmetic tasks, by the use of noninvasive measures of sympathetic (pre-ejection period; PEP) and parasympathetic (respiratory sinus arrhythmia; RSA) cardiac control. As previously demonstrated, mental arithmetic was associated with a reciprocal pattern of sympathetic activation and vagal withdrawal. The illusion task, however, yielded a distinct mode of vagal activation in the absence of sympathetic change. Responses within tasks were reliable. In contrast to the general intertask consistency reported for stress tasks that yield similar autonomic modes of response, however, neither PEP nor RSA responses were correlated across the illusion and arithmetic tasks. This may be attributable to the dissimilar modes of autonomic control evoked by these tasks. The distinct modes of autonomic response to arithmetic and illusions emphasize the importance of a bivariate model of autonomic control, and may offer important experimental tools for psychophysiological studies of autonomic control.

Autonomic cardiac control. II. Noninvasive indices and basal response as revealed by autonomic blockades.

Heart period, systolic time intervals, low and high frequency heart period variability, blood pressure, and respiration were measured in female subjects under three drug conditions (saline, atropine sulfate, metoprolol) while sitting and standing on three consecutive days. Following preinfusion baseline recordings, saline, metoprolol (14 mg), or atropine sulfate (2 mg) was infused for 15 min (by using a double-blind procedure). Recordings were taken during a postinfusion baseline and in response to an orthostatic stressor (standing versus sitting postures). At the end of the metoprolol session, atropine sulfate was infused and responses were monitored during the postinfusion (i.e., double blockade) baseline and during orthostatic stressor. Analyses of the blockade data revealed that the preejection period (PEP) reflected sympathetic but not vagal influences on the heart, and high frequency (HF, 0.12-0.40 Hz) heart rate variability (respiratory sinus arrhythmia) reflected vagal but not sympathetic influences on the heart. No other measure provided a specific index of the tonic sympathetic or vagal activation of the heart. Postinfusion PEP under saline predicted individual differences in postinfusion cardiac sympathetic activation, whereas postinfusion heart period (but not HF variability) under saline predicted individual differences in postinfusion cardiac vagal activation.

Autonomic cardiac control. III. Psychological stress and cardiac response in autonomic space as revealed by pharmacological blockades.

Behavioral contexts can evoke a variety of autonomic modes of response, characterized by reciprocal, coactive, or independent changes in the autonomic divisions. In the present study, we investigated the reactive autonomic control of the heart in response to psychological stressors, using quantitative methods for analyzing single and double autonomic blockades, and through the use of noninvasive indices based on heart period variability and systolic time intervals. Analysis of the effects of pharmacological blockades revealed an overall pattern of increased sympathetic and decreased parasympathetic control of the heart during speech stress, mental arithmetic, and a reaction-time task. Unlike the classical reciprocal sympathetic-parasympathetic response to orthostatic challenge, however, the responses of the autonomic branches to stress were uncorrelated. This reflected notable individual differences in the mode of autonomic response to stress, which had considerable stability across stress tasks. The putative noninvasive indices of sympathetic (preejection period) and parasympathetic (respiratory sinus arrhythmia) control changed in accord with the results of pharmacological blockades. Together, these results emphasize the substantial individual differences in the mode of autonomic response to stress, the advantages of a quantitative approach to analyzing blockade data, and the importance of validity estimates of blockade data.