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Biomedical subjects

H E Gwirtsman

Publications and source records attributed to H E Gwirtsman.

At least 19 recordsLinked to original sources

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

Pituitary-adrenal-immune system in normal subjects and in patients with anorexia nervosa: the number of circulating helper T lymphocytes (CD4) expressing the homing receptor Leu8 is regulated in part by pituitary-adrenal products.

The association between plasma pituitary-adrenal (PA) hormones and the number of certain populations of peripheral blood lymphocytes (PBL) was examined in subjects with normal PA function and in patients with anorexia nervosa (AN). AN patients display several neuroendocrine dysfunctions, including hypercortisolemia. In the normal subjects there were positive correlations between adrenocorticotropic hormone (ACTH) and the number of PBL and helper T lymphocytes expressing the homing receptor Leu8 (CD4+Leu8+); there was a negative relationship between cortisol and these lymphocyte populations. These latter, inverse correlations did not occur in the AN patients, either while underweight or after weight recovery, with some persistence of hypercortisolemia. Administration of dexamethasone (DEX) suppressed cortisol levels and reduced, perhaps via a receptor-mediated mechanism, the number of circulating PBL and CD4+Leu8+ in the normal subjects but not in the AN patients. These results support the physiological relevance of PA-CMI interaction in subjects with normal PA function and indicate that the PA-CMI interrelationship is disrupted in AN patients with hypercortisolemia.

Adrenocorticotropic Hormone

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

Fluoxetine treatment of anorexia nervosa: an open clinical trial.

Six patients with chronic, refractory anorexia nervosa were treated with fluoxetine. Depressive symptoms diminished in all patients, and this was associated with weight gain. Subjects, despite frequent medical comorbidity, tolerated fluoxetine well, even in dosages greater than those used for depression.

Adult

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

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

Central and peripheral ACTH and cortisol levels in anorexia nervosa and bulimia.

To explore the relationship of central and peripheral adrenocorticotropic hormone (ACTH, or corticotropin) levels to hypothalamo-pituitary-adrenal axis dysfunction in patients with eating disorders, levels of cerebrospinal fluid (CSF) and plasma ACTH, cortisol, and 24-hour urinary free cortisol were measured in 16 patients with anorexia nervosa (60% +/- 1.1% of ideal body weight), 14 patients with bulimia (93.2% +/- 4.6% of ideal body weight), and 11 healthy age-matched women volunteers. The CSF, plasma, and urinary free cortisol levels were elevated in underweight anorexic patients and showed declines following weight recovery. Cortisol-binding globulin levels were similar in anorexics and controls. In contrast, underweight anorexics showed low CSF ACTH levels that returned to normal following weight recovery, and their plasma ACTH levels were normal. On hospital admission, bulimic patients demonstrated normal ACTH and cortisol levels. After their abstinence from binge-purge episodes, the CSF ACTH levels decreased significantly. Positive relationships were found among CSF, plasma, and urinary cortisol levels, and inverse relationships were seen between cortisol measures and CSF ACTH levels in patients with eating disorders. Secretion of ACTH into the CSF may respond to feedback by cortisol or, alternatively, may be suppressed by the hypersecretion of corticotropin-releasing hormone, leading to the depletion of the pro-opiomelanocortin molecule.

Adolescent

Decreased caloric intake in normal-weight patients with bulimia: comparison with female volunteers.

Patients with bulimia (binge-purge syndrome) frequently complain that they consume a very restrictive diet to avoid gaining weight. To investigate this claim, 23 hospitalized bulimic patients were assessed daily for body weight, caloric intake, macronutrient diet content, activity measures, and body composition estimates during weight-stable periods. Bulimic patients ate fewer kilocalories per kilogram body weight (22.1 +/- 4.6 kcal/kg) than did age-matched normal women (29.7 +/- 6.5 kcal/kg) but had similar activity levels and body composition. Clinical variables, such as history of laxative abuse, anorexia, or obesity, and physiological characteristics, such as body weight, activity level, or dietary content, could not account for this difference in caloric consumption. Bulimic patients tended to eat a diet lower in fat and higher in protein than did control subjects. These results agree with observations of increased efficiency of caloric utilization in obese patients and support patient complaints of a tendency to gain weight easily.

Adolescent

Apparent phase advance in diurnal MHPG rhythm in depression.

Several investigators have proposed that diurnal rhythms, particularly that of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), show abnormalities in affective disorders. The present study compared diurnal MHPG rhythms in the plasma of 18 male depressed patients and 12 healthy male volunteers. A diurnal rhythm of MHPG closely fit to a cosine model was observed in volunteers and, to a lesser extent, in depressed patients. Patients, especially those with endogenous depression (N = 11), demonstrated an earlier acrophase (mean +/- SD = 12.53 +/- 3.38 hours), and treatment with desipramine was associated with a significant (3-hour) phase delay. This study confirms and extends previous reports of apparent phase advances in circadian noradrenergic rhythms in depressed patients.

Adult

Hyperamylasemia and its relationship to binge-purge episodes: development of a clinically relevant laboratory test.

Hyperamylasemia and parotid hypertrophy are conditions found in bulimic patients. The authors studied serum amylase levels in 56 underweight anorectics, 24 weight-recovered anorectics, 23 normal-weight bulimics, and 31 volunteer women. Normal-weight bulimic patients had significantly higher admission serum amylase values (mean +/- SE = 73.4 +/- 8.0 IU/L) than controls (40.8 +/- 2.4 IU/L). Additionally, the serum amylase test distinguished between restrictor anorectics (N = 31, 44.7 +/- 4.7 IU/L) and bulimic anorectics (N = 25, 68.8 +/- 8.6 IU/L, p less than .05) with a high degree of specificity and a fair degree of sensitivity. A subsample (N = 7) of bulimics showed twofold to fourfold increases in serum amylase values after a controlled period of binge eating and vomiting, whereas normal volunteers showed no change in serum amylase values (p less than .001) after ingesting a large meal. Serum amylase values declined significantly within 6 to 15 days of admission. However, after passes off the unit, serum amylase values returned to admission values, presumably as a result of binge-vomit episodes. The authors observe that modest increases of serum amylase values appear to be a consequence of binge-vomit behavior and suggest that serial serum amylase determination may be useful in monitoring the degree of patient abstinence in therapeutic programs.

Adult

Contribution of CNS neuropeptide (NPY, CRH, and beta-endorphin) alterations to psychophysiological abnormalities in anorexia nervosa.

Patients with anorexia nervosa have neuroendocrine and behavioral alterations that starvation and weight loss are thought to cause, or contribute to, since they are reversed by weight restoration. We have found that anorexics have starvation-related disturbances of neuropeptide Y (NPY), corticotropin-releasing hormone (CRH), and beta-endorphin, as determined by their measurements in cerebrospinal fluid. The relationship between these neuropeptides and several symptoms in anorexia, together with findings in experimental animals, raise a possibility that changes in the activity of these neuropeptides contribute to neuroendocrine and behavioral alterations in anorexia. Specifically, a disturbance of central nervous system CRH activity is likely to be responsible for hypercortisolemia, while a disturbance of central nervous system NPY may contribute to amenorrhea. In addition, disturbances of these neuropeptides could contribute to other symptoms such as increased physical activity, hypotension, reduced sexual interest, depression, and pathological feeding behavior.

Adult

Energy intake and dietary macronutrient content in women with anorexia nervosa and volunteers.

This study was designed to compare the dietary intakes of patients with anorexia nervosa and normal controls. Twenty-four patients hospitalized for treatment of anorexia nervosa were compared with 10 normal controls. Patients ate a self-selected diet and maintained their admission weight to within 1.0 kg during this period (19 +/- 3 days). Food chosen by each subject was weighed before and after meals, and intake was determined to be the difference. Intakes of food energy, protein, fat, and carbohydrate were calculated. Patients were closely monitored to ensure that no disposal of food occurred. Patients with anorexia nervosa had a mean daily energy intake of 1,017 +/- 54 kcal (mean +/- SEM), significantly lower than the mean energy intake for controls (1,651 +/- 108 kcal). Similarly, mean intakes of macronutrients (41 +/- 4 gm protein, 34 +/- 2 gm fat, and 136 +/- 9 gm carbohydrate) were significantly lower for patients than for controls (68.5 +/- gm protein, 65 +/- 6 gm fat, and 204 +/- 13 gm carbohydrate). However, when protein, fat, and carbohydrate were assessed as a percent of total calories, there were no significant differences between patients and controls. There were also no significant differences in calories consumed per kilogram body weight. Underweight patients with anorexia nervosa who maintain their weight on an unrestricted hospital diet have energy intake per kilogram body weight and dietary macronutrient content indistinguishable from those of normal women.

Adult

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

CSF somatostatin in anorexia nervosa and bulimia: relationship to the hypothalamic pituitary-adrenal cortical axis.

The eating disorders, anorexia nervosa and normal weight bulimia, are associated with disturbances of hypothalamic-pituitary-adrenal cortical (HPA) and growth hormone function. Because somatostatin (SRIF) is one of the neuropeptides known to modulate feeding behavior and neuroendocrine systems, we measured cerebrospinal fluid (CSF) concentrations of this peptide in patients with eating disorders. CSF SRIF concentrations in patients with anorexia nervosa, both at low weight and after weight recovery, were similar to those in controls. When normal weight bulimic women stopped binging, they had a modest but significant increase in CSF SRIF. CSF SRIF was not related to plasma growth hormone concentrations but did show relationships to HPA axis hormones. Healthy volunteer women had a significant positive relationship between CSF SRIF and CSF corticotropin releasing hormone (CRH). In underweight anorectics, CSF SRIF was negatively related to both 24-hr urinary free cortisol and plasma cortisol concentrations after dexamethasone, but it was not significantly related to CSF CRH. These relationships more closely resembled those of healthy controls after weight correction. In bulimics, CSF SRIF was positively related to CSF CRH and negatively related to plasma cortisol. Our findings support a previously described relationship between CSF SRIF and HPA axis activity. The differences in SRIF-HPA relationships in anorectics and bulimics may constitute or reflect pathophysiological distinctions between these disorders.

Adult

Relative importance of calorie intake needed to gain weight and level of physical activity in anorexia nervosa.

We assessed whether level of physical activity of anorexia nervosa patients could influence caloric consumption needed to gain weight during hospitalization. Seventy-three percent of patients with anorexia nervosa had higher levels of motor activity than did healthy female volunteers. Anorectics required 8301 +/- 2272 kcal (mean +/- SD) to gain 1 kg body wt. Activity levels and caloric consumption needed to gain 1 kg were significantly correlated; the most active patients needed to consume more calories to gain weight. A median split of anorectic patients by level of activity showed that the group with lower activity levels gained 1 kg every 5.1 +/- 1.2 d, whereas the group with higher activity levels gained 1 kg every 7.2 +/- 1.9 d. These data suggest that the rate of weight gain can be accelerated, and the cost of hospitalization decreased, by restricting exercise in anorectics during refeeding.

Adult