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Biomedical subjects

T D Brewerton

Publications and source records attributed to T D Brewerton.

At least 19 recordsLinked 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

Neuroendocrine responses to m-chlorophenylpiperazine and L-tryptophan in bulimia.

Preclinical and clinical evidence supports a theory of serotonin (5-hydroxytryptamine [5-HT]) dysregulation in bulimia. We therefore studied the prolactin (PRL) and cortisol responses following challenges with the postsynaptic 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg orally, the 5-HT precursor L-tryptophan, 100 mg/kg intravenously, and placebo in a group of 28 normal weight bulimic patients and 16 healthy controls. Patients with bulimia, regardless of the presence of major depression, had significantly blunted PRL responses following m-CPP administration compared with those in controls. In contrast, only bulimic patients with concurrent major depression had significantly blunted PRL responses following L-tryptophan administration compared with those in nondepressed bulimic patients and controls. Cortisol responses following m-CPP were not significantly different for bulimic patients vs controls, although there was a trend toward blunted cortisol responses following L-tryptophan administration in the depressed bulimic patients. These differences in neuroendocrine responses were not related to differences in age, percent of average body weight, medications, time of day, peak plasma drug levels, or baseline estradiol levels. Seasonal variations in PRL responses to both agents were identified, although covariation for season did not alter the group differences. The PRL responses following m-CPP administration were inversely correlated to baseline cortisol levels in the bulimic patients, but not in the controls, suggesting a dampening effect by hypothalamic-pituitary-adrenal axis dysfunction on postsynaptic 5-HT receptor sensitivity. The reasons for the differing hormonal responses to these two serotonergic agents may relate to differential involvement of presynaptic and postsynaptic mechanisms, 5-HT receptor subtypes, and anatomical loci of action. The blunted PRL responses to m-CPP administration suggest that postsynaptic 5-HT receptor sensitivity is altered in bulimia nervosa, and that similar alterations in 5-HT receptors at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms.

Adult↗
PubMed1992

Headache responses following m-chlorophenylpiperazine in bulimics and controls.

We have previously reported that the serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) induced late occurring migraine-like headaches in a group of patients with eating disorders and controls (n = 52). In this report, we extend our analyses of these data and describe results indicating that headache responses following m-CPP are greater in patients with bulimia nervosa than controls, regardless of the presence of anorexia nervosa or major depression. Although patients with severe migraine-like headaches had higher peak m-CPP levels than patients without severe headaches, these levels are not higher than other groups studied who did not get headaches. These findings suggest that post-synaptic 5-HT receptor sensitivity is altered in the vascular tissues of bulimic patients. Additional disturbances in 5-HT function, perhaps presynaptic ones, may be associated with anorexia nervosa and major depression. Similar alterations in other 5-HT pathways at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms of bulimia nervosa. Further studies exploring the functional integrity of 5-HT receptors and their subtypes are warranted in bulimic patients, as well as in patients with nonbulimic anorexia nervosa, minor and major depression without an eating disorder, and migraine and other headache patients.

Anorexia Nervosa↗
PubMed1992

CSF beta-endorphin and dynorphin in bulimia nervosa.

OBJECTIVE: Preclinical and clinical evidence suggests that central opioid dysfunction may play a role in the pathophysiology of the eating disorders. In particular, endogenous opioids are known to regulate feeding behavior, mood, perception, and neuroendocrine function, all of which are disturbed in patients with eating disorders. Although low concentrations of CSF beta-endorphin have been reported in low-weight patients with anorexia nervosa, central opioid activity in normal-weight patients with bulimia nervosa has not been reported. The authors therefore measured CSF concentrations of beta-endorphin and dynorphin in drug-free female patients with DSM-III-R-defined bulimia nervosa and normal comparison subjects. METHOD: After 4 days of a low monoamine diet and overnight bed rest, CSF was obtained (12-26 cc) from 11 women with bulimia and 17 normal comparison subjects (eight women and nine men). RESULTS: The women with bulimia had significantly lower CSF concentrations of beta-endorphin than did the female comparison subjects. However, CSF concentrations of dynorphin were not significantly different in patients and female or male comparison subjects. beta-Endorphin concentrations were inversely correlated with Beck Depression Inventory scores and the depression subscale of the Eating Disorders Inventory. CONCLUSIONS: These data support a role for central opiates in the mediation of the pathophysiology of the signs and symptoms of bulimia nervosa, although it is impossible to rule out the effects of depression on the results.

Adult↗
PubMed1991

Fluoxetine-induced suicidality, serotonin, and seasonality.

In spite of the complexities involved in suicide, fluoxetine has been prematurely and simplistically blamed for inducing this phenomenon. A variety of variables must be factored into such an interpretation. Nevertheless, given the complicated psychobiological circumstances involved, acute and rapid changes in serotonin (5-HT) function appear to be important to the understanding of changes in suicidal behavior. Such a mechanism may also explain the robust seasonal peak of suicides in spring.

Adult↗
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

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

A study of the seasonal variation of migraine.

Available evidence supports the contention that migraine involves a disturbance in serotonin function. Several parameters of serotonin function in humans have been found to vary seasonally and may underlie the seasonal fluctuations observed in many clinical neuropsychiatric phenomena that are thought to involve serotonin dysfunction. We therefore postulated that migraine headaches might also vary seasonally and examined the admissions to our hospital over a 20-year period with a primary diagnosis of migraine. Peak admissions were found to occur most frequently in the spring for females in comparison to males (p less than or equal to 0.04, chi-square). The implications of these findings are discussed.

Chi-Square Distribution↗
PubMed1990

Serotonin in human eating disorders.

The onset and progression of symptomatology in patients with anorexia nervosa and bulimia nervosa is complex. It is unlikely that dysregulation of a single neurotransmitter system would be sufficient to explain the pathophysiology of these disorders. The studies reviewed above provide preliminary evidence that decreased central serotonin function may contribute to the onset or persistence of binge eating episodes in patients with bulimia nervosa, including low weight anorexic patients with bulimic symptoms. Future clinical studies will benefit from the availability of selective serotonin receptor agonists and antagonists. Longitudinal studies through progressive phases of treatment and clinical remission will be important to clarify the contribution of dietary and body weight changes to results of neurotransmitter studies with eating disorder patients.

Anorexia Nervosa↗
PubMed1990

Relation of clinical variables to dissociative phenomena in eating disorders.

In this study 30 female patients with eating disorders were compared with 30 age-matched normal female subjects. The patients demonstrated significantly higher levels of dissociative psychopathology than the comparison subjects. Furthermore, the presence of severe dissociative experience appeared to be specifically related to a propensity for self-mutilation and suicidal behavior. These findings are discussed in light of recent data which suggest that neurochemical systems shown to be abnormal in patients with eating disorders may be key pathophysiologic substrates for dissociative experience.

Adolescent↗
PubMed1988

Analysis of seasonal fluctuations of CSF monoamine metabolites and neuropeptides in normal controls: findings with 5HIAA and HVA.

Seasonal variations of certain cerebrospinal fluid (CSF) parameters have been reported in several psychiatric patient groups, but there is little or no available information on such variations in normal individuals. To evaluate possible circannual variations in the major CSF monoamine metabolites and an array of neuropeptide measures, we analyzed data from 20 to 34 normal volunteers studied over a 3-year period. Data were analyzed for seasonal and cross-seasonal fluctuations by one-way analysis of variance (ANOVA) followed by Bonferroni t tests when appropriate. The only statistically significant findings by ANOVA were for CSF 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA), both of which were lowest during spring and highest during summer. These spring-summer differences were statistically significant following Bonferroni t tests. These data support a growing body of evidence indicating a substantial seasonal effect on the serotonin system and suggest that any group analysis of CSF 5HIAA, and perhaps HVA, should take into account circannual variability.

Brain↗
PubMed1988

Bingeing behavior and plasma amino acids: a possible involvement of brain serotonin in bulimia nervosa.

It has been suggested that bingeing and vomiting behavior may be an attempt to suppress hunger or reduce dysphoria. Theoretically, such relationships could involve a mechanism whereby bingeing and vomiting change plasma amino acids which, in turn, enhance brain serotonin-mediated satiety and/or improvement in mood. This hypothesis is based on data showing that the intake of dietary carbohydrates increases the uptake of tryptophan (TRP), the precursor of serotonin, into the brain by increasing the plasma TRP ratio (the ratio of the plasma TRP concentration to the summed concentrations of other amino acids that compete with TRP for brain uptake). Plasma prolactin (PRL) release might reflect the activation of this system. We found that an increase in the TRP ratio during bingeing and vomiting was associated with satiety (i.e., cessation of bingeing and vomiting), but not change in mood. In other words, bulimic subjects who developed an increased plasma TRP ratio during bingeing and vomiting had fewer cycles of bingeing and vomiting and a greater increase in plasma PRL than did subjects who did not develop an increase in the plasma TRP ratio. This study raises the possibility that an increase in the TRP ratio may be associated with the termination of bingeing and vomiting, perhaps due to its effects on brain serotonin metabolism.

Amino Acids↗
PubMed1988

Induction of migrainelike headaches by the serotonin agonist m-chlorophenylpiperazine.

In a study of serotonin (5-HT) function in patients with eating disorders and healthy control subjects, severe headaches with features of common migraine occurred unexpectedly in 28 of 52 subjects (54%) 8 to 12 hours after receiving a single oral dose of the 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg. None of the same subjects developed similar late-occurring headaches after placebo or the 5-HT precursor, L-tryptophan, 100 mg/kg given intravenously. The frequency of these migrainelike headaches was not significantly different between patients with bulimia or anorexia nervosa and control subjects, but incidence of headaches was significantly greater in subjects with a personal or family history of migraine, with almost all predisposed individuals (18 of 20, 90%) developing severe symptoms. Headache ratings were also significantly correlated (rho = 0.70; p less than 0.0001) with peak concentrations of m-CPP in plasma. These observations indicate that m-CPP may provide a novel probe for studies of the pathophysiology of migraine headaches.

Adult↗