Decreased serotonin function in bulimia nervosa.

BACKGROUND: Evidence that serotonin-active antidepressant medications decrease binge eating in patients with bulimia nervosa has fueled interest in the hypothesis that abnormal serotonergic neurotransmitter function contributes to symptoms of the disorder. To evaluate this hypothesis, we employed pharmacological challenge testing to compare serotonin function in patients with bulimia nervosa and healthy controls. METHODS: Neuroendocrine response patterns were compared for 15 nonhospitalized, medication-free, normal-weight women with bulimia nervosa and 14 age-matched healthy female controls. Behavioral assessment included ratings of eating disorder symptoms, depression, and anxiety. Serotonergic response patterns were assessed by measuring the increase in serum prolactin concentration during 5 hours following single-dose, oral administration of 60 mg of d,l-fenfluramine hydrochloride (Pondimin). RESULTS: For patients with bulimia nervosa, the fenfluramine-stimulated increase in serum prolactin concentration was significantly less than for controls. Within the patient group, the frequency of binge eating episodes during the 4 weeks prior to the study exhibited a significant inverse correlation with serotonin-stimulated prolactin secretion. CONCLUSION: Our study provides new evidence that impaired central nervous system serotonergic responsiveness may contribute to the onset or maintenance of abnormal eating patterns in patients with bulimia nervosa.

Decreased serum leptin in bulimia nervosa.

The eating disorder bulimia nervosa has been associated with impaired satiety, decreased resting metabolic rate, and abnormal neuroendocrine regulation. Preclinical studies suggest that such alterations could be associated with impaired leptin function. Thus, the goal of this study was to assess whether leptin function is decreased in bulimia nervosa. Serum leptin levels measured in women with bulimia nervosa (n = 18) and in women who had maintained stable recovery from bulimia nervosa (n = 15) were compared with values in healthy female controls (n = 20). Subjects were studied during the follicular phase of their menstrual cycle after an overnight fast and bed rest. Baseline serum samples were analyzed for leptin concentration by RIA. Subject groups were matched for age and body weight. Analysis of covariance, adjusting for percent body fat, demonstrated abnormally low serum leptin levels in the bulimia nervosa group (P: = 0.02), with a trend toward an inverse correlation between frequency of binge episodes and serum leptin concentration (P: < 0.1). Additionally, the remitted patient group demonstrated abnormally low leptin values (P: = 0.01). These results are consistent with the hypothesis that decreased leptin function may be associated with alterations in eating patterns, metabolic rate, and neuroendocrine regulation in bulimia nervosa.

Salivary gland enlargement and elevated serum amylase in bulimia nervosa.

BACKGROUND: Clinical reports have described salivary gland enlargement in bulimia nervosa, particularly in patients with elevated serum amylase concentration. The goal of the current study was to provide a controlled comparison of salivary gland size in patients with bulimia nervosa and healthy volunteers. METHODS: Subjects included 17 women with bulimia nervosa and 21 healthy female control subjects. Dimensions of the parotid and submandibular salivary glands were estimated by ultrasonography. Blood samples for amylase measurement were obtained after overnight fast. RESULTS: Parotid gland size was enlarged 36% in patients with bulimia nervosa in comparison to control subjects (p < .01). For the patient group, salivary gland size was significantly correlated with frequency of bulimic symptoms and with serum amylase concentration. CONCLUSIONS: These results provide new quantitative data demonstrating increased salivary gland size in bulimia nervosa. Further studies are needed to evaluate factors responsible for salivary gland enlargement and hyperamylasemia in this disorder.

Serotonin function following remission from bulimia nervosa.

Abnormal serotonergic regulation in bulimia nervosa is thought to contribute to recurrent binge eating, depressed mood, and impulsivity. To follow-up on previous studies showing decreased neuroendocrine responses in symptomatic patients, this study assessed serotonin-mediated prolactin responses in individuals who had remitted from bulimia nervosa. Subjects included 21 women with a history of bulimia nervosa and 21 healthy female controls, as well as an additional comparison group of 19 women with current bulimia nervosa. Placebo-controlled neuroendocrine response studies utilized a single oral dose (60 mg) of the indirect serotonin agonist d,l-fenfluramine. For the bulimia nervosa remitted group, the fenfluramine-stimulated elevation in serum prolactin concentration was not significantly different from the response in healthy controls, but was significantly larger than the response in patients with current bulimia nervosa (p < .01). These findings suggest that diminished serotonergic neuroendocrine responsiveness in bulimia nervosa reflects a state-related abnormality. The results are discussed in relationship to recent reports indicating that some alterations in central nervous system serotonin regulation may persist in symptomatically recovered individuals.

Medications in the treatment of eating disorders.

Effective planning for medication treatment in patients with bulimia nervosa and anorexia nervosa is based on a comprehensive clinical assessment, including a careful review of comorbid psychiatric disorders and response to treatments for previous episodes of the disorder. Although most patients with bulimia nervosa are offered a trial of psychotherapy, significant results of controlled trials have contributed to an increased role for medications in the treatment of patients with this disorder. Pharmacologic treatment of anorexia nervosa has similarities to that of treatment-resistant depression, with the clinician turning to open trials and clinical reports for clues to rational management. As described in this article, considerations of potential side effects and medical complications are likely to play an important role in guiding the choice of medication used for treatment of patients with eating disorders.

Comparison of the effects of amino acid mixture and placebo on plasma tryptophan to large neutral amino acid ratio.

To assess the possible role of altered central serotonin function in psychiatric disorders, investigators have utilized pharmacological challenge testing with an amino acid mixture to decrease blood tryptophan concentration and, indirectly, brain serotonin levels. The aim of this pilot study was to assess the effectiveness of a modified amino mixture, administered in capsule form, in decreasing plasma tryptophan levels. Studies were conducted in six healthy, medication-free female volunteers. Following double-blind, randomized, cross-over design, subjects received on separate days capsules containing a tryptophan-free amino acid mixture (31.5 grams) or lactose placebo. Over the six hours following amino acid administration, plasma tryptophan concentrations decreased to 21% of baseline values, while the tryptophan/large neutral amino acid ratio decreased to 6% of baseline. Subjects reported minimal symptoms of nausea or other side effects following amino acid administration. The results suggest that the modified amino acid mixture may be useful in assessing behavioral responses to acute tryptophan depletion challenge testing.

The effects of dieting on plasma tryptophan concentration and food intake in healthy women.

Although many people diet, relatively few dieters are successful in maintaining weight loss. The extent to which dieting behavior might dampen satiety responses normally mediated by the neurotransmitter serotonin remains uncertain. This study tested the hypothesis that dieting behavior decreases the availability of plasma tryptophan (TRP) and the ratio of TRP to other branched-chain amino acids (BCAA) that compete for entry into the central nervous system (CNS). This effect could diminish the CNS concentration of TRP, the amino acid precursor for serotonin synthesis, thus interfering with serotonin-mediated influences on food intake. Using a fixed-order design, 15 healthy, normal-weight women were studied longitudinally during an ad lib dietary intake phase and subsequent reduced-calorie diet phase. Physiological and behavioral measures were collected at baseline, at the end of the ad lib-intake phase, and at the end of the 4-week study diet phase. Food intake was measured by a single-item test meal. Plasma TRP and TRP: sigma BCAA significantly decreased following the study diet compared to baseline (p < 0.05). Change in TRP and TRP: sigma BCAA significantly correlated with decrease in body weight (p < 0.01). No significant relationship was observed between postdiet change in TRP or TRP: sigma BCAA ratio and postdiet change in test meal food intake, with covariation for weight loss. The observed decreases in plasma TRP and TRP: sigma BCAA extend previous reports suggesting that dieting behavior may diminish central serotonin function through a reduction in precursor availability.

Laboratory screening for electrolyte abnormalities and anemia in bulimia nervosa: a controlled study.

OBJECTIVE: Abnormal eating patterns and recurrent purging behaviors can result in significant medical complications. The purpose of this study was to assess the frequency of abnormalities in clinical laboratory tests in patients with bulimia nervosa who reported being otherwise in good health. METHODS: Subjects included nonhospitalized women (N = 74) who met criteria for bulimia nervosa outlined in the 3rd Rev. ed. of the Diagnostic and Statistical Manual of Mental Disorders. They also reported use of self-induced vomiting and/or laxatives as compensatory behaviors (purging subtype). The control group (N = 110) included female volunteers with no history of a psychiatric disorder. All subjects reported being in good medical health, were medication free, and were in a normal weight range. Blood samples were analyzed in the hospital clinical laboratory. RESULTS: Compared with controls, patients showed more frequent occurrence of low values for serum potassium (6.8% vs. 0.9%; p <.05) and chloride (8.1% vs. 0.9%; p <.02). Electrolyte abnormalities occurred most often in patients with frequent bulimic episodes. Study groups did not differ significantly in frequency of abnormal hemoglobin concentrations. DISCUSSION: These results help to clarify the expected frequency of electrolyte abnormalities in individuals with bulimia nervosa who report otherwise good medical health. The substantial frequency of hypokalemia and hypochloremia underscores the importance of an appropriate medical assessment for individuals with this disorder.