Biomedical subjects

W H Kaye

Publications and source records attributed to W H Kaye.

At least 91 records · Page 5Linked to original sources

PubMed1992

Low serotonin and dopamine metabolite concentrations in cerebrospinal fluid from bulimic patients with frequent binge episodes.

Cerebrospinal fluid neurotransmitter metabolite levels were studied to assess whether measures of central serotonin, dopamine, or norepinephrine function are associated with severity of abnormal eating patterns in patients with bulimia nervosa. In comparison with healthy controls (N = 17), hospitalized bulimic patients with a history of binge eating more frequently than twice daily (N = 11) had significantly lower CSF concentrations of 5-hydroxyindoleacetic acid and homovanillic acid. For the total patient group (N = 29), levels of both metabolites were significantly inversely correlated with binge frequency. On the basis of preclinical studies, these results were examined in the context of speculative models in which low central serotonin function might contribute to blunted satiety responses in bulimic patients, while low central dopamine activity might play a role in abnormal hedonic responses to food.

Adult↗

PubMed1992

Laboratory assessment of feeding behavior in bulimia nervosa and healthy women: methods for developing a human-feeding laboratory.

We have designed a human-feeding laboratory to be used to study feeding behavior in patients with eating disorders. Twenty-one normal-weight bulimic subjects consumed 29.711 +/- 39.940 MJ (range 0.862-178.632 MJ; 7101 +/- 9546 kcal, range 206 to 42,694 kcal) in 24 h. In comparison, 11 healthy volunteer women, when instructed to eat ad lib for 48 h, ate 7.715 +/- 2.590 MJ (1844 +/- 619 kcal) during the first 24 h and 7665 +/- 1828 MJ (1832 +/- 437 kcal) during the second 24 h. Bulimics and control subjects had a similar number of eating intervals (6.6 +/- 2.6 vs 5.0 +/- 1.7); 72% of the bulimic subjects' meals were similar in size to the meals of the controls [167-4100 kJ (40-980 kcal)] but these meals were higher in carbohydrate and lower in fat in bulemic patients. Excessive caloric intake by bulimic subjects was because 28% of their meals were very large [range 4.427-28.150 MJ (1058-6728 kcal)]. Data gathered in a laboratory setting appears to be a reasonable replication of naturalistic feeding and suggest that such a laboratory may prove useful for future studies of feeding behaviors in humans.

Adult↗

PubMed1991

Feeding patterns in bulimia nervosa.

We characterized the naturalistic feeding patterns of 54 women with bulimia nervosa and 11 matched controls over a continuous 24-hr period in a feeding laboratory. Overall, bulimic women consumed more calories in 24 hr (4446 +/- 584 kcal) than did controls (1845 +/- 649 kcal). Bulimic women consumed a wide range of caloric intake, with 44% overeating and 19% undereating in comparison to the range of controls. In addition, bulimics showed a disruption of circadian feeding patterns. For overeating bulimic women, the majority of meals were of normal size and frequency. Increased caloric intake in the group of overeating bulimic women was mainly due to the fact that 37% of their meals were greater than 1000 calories. Large meals occurred predominantly during the afternoon and evening and consisted primarily of dessert and snack foods. Importantly, the percentage of fat, but not carbohydrates, consumed increased as meal size, and 24-hr caloric intake increased. This study is the first to describe the naturalistic feeding characteristics of a large number of bulimics by direct observation. These findings are consistent with previous self-reports and extend and replicate previous laboratory studies. We think that laboratory studies are a reasonable replica of naturalistic feeding and should facilitate further investigation of the psychological and physiological correlates of feeding behavior in eating disorders.

Adolescent↗

PubMed1991

Circadian patterns of cortisol, prolactin, and growth hormonal secretion during bingeing and vomiting in normal weight bulimic patients.

Women who are of normal weight and have bulimia nervosa exhibit multiple neuroendocrine disturbances. We hypothesized that bingeing and vomiting behavior could be contributory because food consumption in healthy volunteers increases plasma cortisol and prolactin secretion and suppresses growth hormone secretion. Thus, we investigated the effects of bingeing and vomiting on the circadian pattern (measurements every 20 min for 24 hr) of these hormones in comparison to healthy control women eating normally. Bingeing and vomiting were associated with modest increases in cortisol and prolactin and reductions in growth hormone secretion. However, this bingeing or purging did not alter mean 24-hr pattern of cortisol and growth hormone secretion as values for bulimics were similar to controls. While mean daytime patterns of prolactin secretion were similar in bulimics and controls, bulimic patients had a significant reduction of nocturnal prolactin levels. In summary, bingeing and vomiting does not appear to have a substantial influence on hormonal secretion. However, bulimic women have blunted nocturnal prolactin patterns.

Adolescent↗

PubMed1991

Measurement of CSF dynorphin A 1-8 immunoreactivity in anorexia nervosa and normal-weight bulimia.

Twenty-one patients with anorexia nervosa and 35 normal-weight patients with bulimia underwent a series of CSF studies involving measurement of CSF dynorphin A 1-8 immunoreactivity during hospitalization in an eating-disorder treatment and research program. The control group consisted of 17 healthy volunteers. There were no statistically significant differences in CSF dynorphin A 1-8 measurements among groups or within a group at various stages of treatment. These results regarding dynorphin A 1-8 immunoreactivity are discussed in light of other evidence for altered opiate function in some eating-disorder patients.

Adult↗

PubMed1991

Altered serotonin activity in anorexia nervosa after long-term weight restoration. Does elevated cerebrospinal fluid 5-hydroxyindoleacetic acid level correlate with rigid and obsessive behavior?

To avoid the confounding influences of malnutrition or weight loss, we studied patients with anorexia nervosa at normal weight and stable dietary intake. Compared with 15 controls, 17 long-term weight-restored anorectic subjects had elevated concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid, the major serotonin metabolite, whereas levels of cerebrospinal fluid homovanillic acid, the major dopamine metabolite, were normal. Elevated levels of cerebrospinal fluid 5-hydroxyindoleacetic acid may indicate increased serotonin activity. Such activity could contribute to pathological feeding behavior. Most importantly, this study raises the question as to whether increased cerebrospinal fluid 5-hydroxyindoleacetic acid levels are associated with overly inhibited, anxious, or obsessive traits.

Adult↗

PubMed1991

Abnormal caloric requirements for weight maintenance in patients with anorexia and bulimia nervosa.

OBJECTIVE: This study tested previous findings that patients with eating disorders who attain normal weight have abnormal caloric requirements for maintaining weight. METHOD: Fifty-three female patients meeting the DSM-III-R criteria for anorexia nervosa and/or bulimia nervosa were divided into four subgroups, and their daily caloric intake was measured over a weight-stable period. Patients with anorexia nervosa (restricting and bulimic subtypes) were studied 4 weeks after refeeding and weight gain, when they had attained 95% of average body weight. Patients with normal-weight bulimia (previously anorexic or never previously anorexic) were studied 1-4 weeks after admission to an inpatient unit. RESULTS: After weight restoration, restricting anorexic patients required significantly more calories per day to maintain weight than did bulimic anorexic patients, as measured with corrections for weight, body surface area, and fat-free mass. Previously anorexic normal-weight bulimic patients required significantly more calories per day to maintain weight than never-anorexic normal-weight bulimic patients, as measured with correction for weight but not with the other factors used to correct caloric intake. CONCLUSIONS: To maintain stable weight after weight restoration, restricting anorexic patients require a significantly higher caloric intake than do bulimic anorexic patients. Differences in caloric needs between normal-weight bulimic patients with and without histories of anorexia may depend on the methods used to correct caloric requirements. Body surface area may be the most precise correction factor across different subgroups of eating disorder patients. Elevated caloric requirements, when coupled with reduced food intake, may particularly contribute to relapse in anorexic patients.

Adolescent↗

PubMed1991

Slowing of pulsatile luteinizing hormone secretion in men after forty-eight hours of fasting.

To determine whether short periods of fasting can suppress the activity of the reproductive axis in normal healthy men, eight men were studied on a fed day and again after 48 h of fasting. Subjects were between 20-32 yr of age and ranged from 84-119% of normal body weight. Blood samples were collected on day 1 (a fed day) and day 3 (after 48 h of fasting) at 15-min intervals from 0800-1600 h through indwelling venous catheters. Fasting for 48 h resulted in a significant decrease in mean LH, FSH, and testosterone concentrations. The mean LH concentration decreased from 2.94 +/- 0.59 IU/L on the fed day to 1.07 +/- 0.14 IU/L after 48 h of fasting, and there was an accompanying decrease in LH pulse frequency (from 5.13 +/- 0.29 to 2.63 +/- 0.62 pulses/8 h) and mean baseline LH concentration (from 1.83 +/- 0.52 to 0.51 +/- 0.07 IU/L), but no significant decrease in LH pulse amplitude. In a second study, blood samples were collected from five subjects who were allowed to eat normally between days 1 and 3; these individuals showed no difference in LH secretion. To begin to examine the possibility that an activation of the hypothalamic-pituitary-adrenal axis leads to the suppression of reproductive hormone levels that occurred after 48 h of fasting, cortisol levels were measured in all plasma samples. There was no significant difference in mean cortisol concentrations on fed vs. fasted days or when cortisol concentrations were examined as hourly means across the 2 days. These results indicate that activity of the reproductive axis can be suppressed in normal healthy men by 48 h of fasting. It appears unlikely that activation of the adrenal axis is the cause of this suppression of reproductive axis activity.

Adult↗

PubMed1991

Neurochemistry of bulimia nervosa.

Normal weight bulimia nervosa, a disorder of unknown etiology, is characterized by bingeing and purging behavior, disturbances of mood, and neuroendocrine abnormalities. Bulimic women have alterations of neurotransmitter systems known to contribute to the modulation of feeding, mood, and neuroendocrine function. Bulimic patients have increased cerebrospinal fluid concentrations of peptide YY (PYY), a peptide which is a potent stimulant of feeding in experimental animals. It has been suggested that increased brain PYY activity could contribute to the powerful and uncontrollable drive of bulimic patients to binge. It also has been reported that bulimics have impaired satiety and secretion of cholecystokinin, a peptide known to induce satiety and reduce food intake in animals and humans. Most data show that bulimic women have alterations of serotonin and norepinephrine activity. In animals, serotonin appears to have effects on eating behavior (inhibition) that are opposite to the actions of endogenous norepinephrine (activation) at alpha 2 receptors in the hypothalamus. Bingeing behavior is consistent with an overactivity of the hypothalamic alpha-noradrenergic system, an underactivity of hypothalamic serotonergic systems, or a combination of both defects. In summary, it is possible that bulimic patients have a trait-related disturbance of one or more neurotransmitter systems that could cause their appetitive dysregulation. Alternatively, these neurotransmitter disturbances may be secondary to extremes of dietary intake. Nonetheless, such neurotransmitter disturbances may contribute to a high recidivism rate. That is, bulimic patients could enter a vicious cycle in which pathologic feeding sustains and provokes continued pathologic feeding behavior. Moreover, the self-reinforcing effects of bulimia, such as decreased anxiety or food craving, may be mediated through behavior-induced changes in neurotransmission.

Animals↗

PubMed1991

An open trial of fluoxetine in patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa is a disorder of unknown etiology with a high rate of relapse and no known treatment. Because anorexia nervosa shares some similarities with obsessive compulsive disorder, we hypothesized that a serotonin-specific medication might be useful in the treatment of this illness. METHOD: We administered an open trial of fluoxetine to 31 patients with DSM-III-R anorexia nervosa. Most anorexics were started on fluoxetine treatment after inpatient weight restoration and then discharged from the hospital and followed up as outpatients. RESULTS: At the time of follow-up (11 +/- 6 months on fluoxetine), 29 of the 31 patients had maintained their weight at or above 85% average body weight (97% +/- 13% average body weight for the group). We judged response as good in 10, partial in 17, and poor in 4 anorexics as measured by improvements in eating behavior, mood, and obsessional symptoms. Restrictor anorexics responded significantly better than bulimic and/or purging-type anorexics. CONCLUSION: This open trial suggests that fluoxetine may help patients with anorexia nervosa maintain a healthy body weight as outpatients. The reasons for the positive effects of fluoxetine are uncertain, but the agent may help by improving eating behavior and/or reducing obsessionality, depression, and anxiety. It is important to emphasize that this was not a double-blind, placebo-controlled study. Thus we can not be certain of the efficacy of fluoxetine and caution that fluoxetine should not be used as the sole treatment of anorexia nervosa at this time.

Adolescent↗

PubMed1991

Serotonin activity in anorexia and bulimia nervosa: relationship to the modulation of feeding and mood.

Brain serotonin activity contributes to satiety. Theoretically, binging behavior is consistent with reduced serotonin function, whereas anorexia nervosa is consistent with increased serotonin activity. Brain serotonin abnormalities could also contribute to psychopathologic behaviors such as dysphoric mood, disturbance of impulse control, and obsessionality, as well as neuroendocrine disturbances. In fact, disturbances of serotonin have been found in acutely ill anorexia nervosa patients. Tryptophan, an essential amino acid found in the diet, is the precursor of serotonin. Thus serotonin disturbances could be secondary to dietary abnormalities. However, disturbances of serotonin activity appear to persist after long-term weight recovery from anorexia nervosa. While speculative, it is possible that increased serotonin activity could contribute to the pathogenesis of restricted eating and obsessional behaviors in this illness. Physiologic and pharmacologic evidence suggest that patients with normal weight bulimia have reduced serotonin activity when acutely ill. Such disturbances, even if secondary to dietary abnormalities, may still contribute to dysphoric mood and binging behavior.

Affect↗

PubMed1990

Eating disorders and depression: is there a serotonin connection?

Central serotonin pathways modulate eating patterns, and may also participate in the regulation of behavioral impulsivity and mood. Recent studies lend support to the hypothesis that impaired postingestive satiety in bulimia nervosa is associated with reduced hypothalamic serotonergic responsiveness. Serotonin dysregulation has been implicated in major depression, and may play a role in the increased prevalence of depressive episodes in patients with eating disorders. This review compares evidence for alterations in central serotonin regulation in patients with anorexia nervosa, bulimia nervosa, and depression. It is proposed that impaired synaptic transmission in functionally distinct serotonin pathways may result in concurrent or sequential periods of binge eating, behavioral impulsivity, and depression in patients with eating disorders.

Anorexia Nervosa↗

PubMed1990

Disturbances of noradrenergic systems in normal weight bulimia: relationship to diet and menses.

Several lines of evidence suggest that noradrenergic (NE) disturbances occur in normal-weight bulimic patients. The purpose of this study was to investigate factors that may be related to noradrenergic disturbances. First, we measured plasma NE during bingeing and vomiting. We found that this behavior activated the sympathetic nervous system. Bingeing produced a significant increase in the duration and the peak increase of plasma NE when compared with normal controls eating a large meal. Second, we assessed basal peripheral and central NE levels near in time (within several days of hospital admission) to chronic bingeing and vomiting. At this time, bulimics had normal basal plasma and CSF NE levels. Finally, we restudied the same patients after 30 days of inpatient hospitalization and observed abstinence from bingeing and vomiting. In this last state, bulimics had a reduction of basal plasma and cerebrospinal fluid (CSF) NE levels compared with themselves on admission and compared with healthy controls. This study confirms that reduced noradrenergic activity occurs in normal-weight bulimic women and suggests that this abnormality may emerge during abstinence from bingeing. We hypothesize that dietary intake is related to noradrenergic activity, but cause and effect remain uncertain. Noradrenergic disturbances did not appear to be related to weight, depression, physical activity, or amino acid precursors. Lower CSF NE levels were found in amenorrheic bulimic women in both states, suggesting that a noradrenergic disturbance may be associated with the frequent incidence of amenorrhea in bulimic women.

Adult↗

PubMed1990

Altered cerebrospinal fluid neuropeptide Y and peptide YY immunoreactivity in anorexia and bulimia nervosa.

The related central nervous system peptides neuropeptide Y and peptide YY have been found to be among the most potent endogenous stimulants of feeding behavior. We measured these neuropeptides in cerebrospinal fluid to determine whether they contributed to the pathophysiologic characteristics of anorexia and bulimia nervosa. Cerebrospinal fluid neuropeptide Y concentrations were significantly elevated in underweight anorectic patients and in many of the anorectic patients studied at intervals after weight restoration. These levels normalized in long-term weight-restored anorectic patients who had a return of normal menstrual cycles. Increased neuropeptide Y activity may contribute to several characteristic disturbances in anorexia, including menstrual dysregulation. Cerebrospinal fluid peptide YY concentrations were significantly elevated in normal-weight bulimic patients abstinent from pathological eating behavior for a month compared with themselves when actively bingeing and vomiting or compared with healthy volunteers. Increased peptide YY activity may contribute to a drive to overfeed in normal-weight bulimic patients.

Adult↗

PubMed1990

Altered norepinephrine regulation in bulimia: effects of pharmacological challenge with isoproterenol.

While abnormalities in central norepinephrine regulation may contribute to abnormal eating patterns in bulimia nervosa, alterations in function of the peripheral sympathetic nervous system could contribute to the decreased metabolic rate and increased anxiety responses previously reported in these patients. To assess beta-adrenergic receptor sensitivity in bulimic patients, we studied cardiovascular and hormonal responses to acute pharmacological challenge with intravenously administered isoproterenol. In comparison to healthy controls, binge-abstinent bulimic patients had significantly reduced mean baseline plasma norepinephrine level, pulse rate, and systolic blood pressure, and significantly increased chronotropic responses to isoproterenol infusion. Decreased sympathoneural activity may contribute to a tendency for bulimic patients to maintain body weight despite low caloric intake.

Adult↗

PubMed1990

CSF monoamine levels in normal-weight bulimia: evidence for abnormal noradrenergic activity.

Normal-weight bulimic patients have disturbed appetite, mood, and neuroendocrine function and often respond to antidepressants. Since these findings suggest abnormalities in brain monoaminergic pathways, the authors measured CSF monoamine concentrations in 27 normal-weight bulimic patients and 14 volunteers. Bulimic patients had a significantly lower mean CSF norepinephrine concentration. Levels of CSF 5-HIAA, the major serotonin metabolite, and CSF HVA, the major dopamine metabolite, were normal, although more frequent binge-eating in bulimic subjects was associated with a significantly lower CSF HVA level. Whether trait- or state-related, monoaminergic disturbances are part of this disorder's neurobiological syndrome. The lower CSF norepinephrine concentration suggests bulimia is not simply a variant of affective disorders.

Adult↗

PubMed1990

Isoproterenol infusion test in anorexia nervosa: assessment of pre- and post-beta-noradrenergic receptor activity.

Anorexia nervosa is associated with alterations in sympathetic activity and metabolism that persist during and after weight recovery. This study assessed beta-adrenergic receptor activity, an important modulator of vascular and metabolic function, in anorexic patients studied when underweight and at intervals during recovery, in comparison with healthy volunteer women. An increase in heart rate, in response to increasing doses of isoproterenol, served as an index of postsynaptic activity. Anorexic patients, during refeeding and weight gain, needed a significantly higher dose of isoproterenol to increase basal heart rate by 25 beats/minute, compared with underweight anorexic patients. Down-regulated postsynaptic cardiac beta-adrenoceptors during weight gain may protect against refeeding-induced exaggerated sympathetic activity. Because presynaptic beta-adrenoceptors serve as a positive feedback loop for synaptic catecholamine secretion, the increase in plasma norepinephrine concentrations during the isoproterenol infusion served as an index of presynaptic activity. We found that increasing doses of isoproterenol were associated with a linear increase in plasma norepinephrine in each healthy volunteer. In contrast, anorexic patients at any state had a significantly more erratic secretion of plasma norepinephrine in response to increasing doses of isoproterenol. Altered regulation of presynaptic adrenoceptors may explain, in part, the large variance and little consensus between previous studies as to whether anorexic patients have reduced or normal plasma norepinephrine levels.

Anorexia Nervosa↗

PubMed1989

The effect of bingeing and vomiting on hormonal secretion.

Women who are of normal weight and have bulimia nervosa have multiple neuroendocrine disturbances. The reasons for these neuroendocrine abnormalities are not known, but there are reasons to suspect that bingeing and vomiting behavior could be contributory. It is well known that food consumption in healthy volunteers increases plasma insulin, cortisol, and prolactin secretion and suppresses growth hormone secretion, whereas activation of the emetic reflex increases plasma arginine vasopressin (AVP) secretion. The purpose of this study was to investigate the effects of bingeing and vomiting on these hormones. In comparison with healthy control women consuming a large meal, bulimic patients, when bingeing and vomiting, had an exaggerated secretion of either the amount and/or the duration of insulin, cortisol, and prolactin. Vasopressin secretion was not increased during or after bingeing and vomiting, probably because bulimic subjects do not become nauseated. In addition, bulimic patients had significantly reduced baseline plasma prolactin and possibly elevated baseline cortisol compared with controls. In summary, this study supports the presence of neuroendocrine disturbances in bulimia and raises a question as to whether or not excessive and prolonged food consumption (and/or vomiting) are contributory.

Adult↗