Francesca Bortolotti

Persistent amenorrhoea in weight-recovered anorexics: psychological and biological aspects.

Demographic, psychopathological and hormonal parameters of 22 women with previous anorexia nervosa (AN) presently recovered, in a state of stabilized nutritional normalization for 3 months to 2 years but with persistent amenorrhoea, and of 20 psychophysically healthy age- and sex-matched normally menstruating controls were studied. Body mass index (BMI) values did not differ in patients and controls. Psychological examination, monitored by Eating Disorder Inventory 1, Bulimic Investigation Test Edinburgh, Yale-Brown-Cornell Eating Disorder Scale, and Tridimensional Personality Questionnaire rating scales, showed the persistence of some of the psychopathological symptoms of AN. Hormonal examinations included basal plasma concentrations of follicle stimulating hormone, luteotropic hormone, estrogens (E), progesterone, thyrotropic hormone, FT(3), FT(4) (immunoradiometric assays), leptin (LEP) (enzymatic-linked-immunosorbent assay) and 24 h urinary free cortisol (immunoradiometric assay). Hormone values were the same in patients and controls, except for E and LEP levels, which were significantly lower in patients than in controls. The concentrations of the two hormones were not correlated with the BMI of the patients, but LEP values were correlated negatively with the difference between the present BMI and the preanorexic one. The values of both hormones correlated negatively with some of the psychopathological aspects typical of AN, in particular with high body dissatisfaction, ineffectiveness, and interpersonal distrust and with low interoceptive awareness.

Serotonergic dysfunction across the eating disorders: relationship to eating behaviour, purging behaviour, nutritional status and general psychopathology

BACKGROUNDnSeveral recent studies have pointed to a dysfunction of serotonin transmission in patients with eating disorders. Notwithstanding, it is not known whether serotonergic abnormalities are related primarily to eating and/or purging behaviour, nutritional status or general psychopathological dimensions. Therefore, by using a validated neuroendocrine strategy, we investigated central serotonergic function in patients with anorexia nervosa, bulimia nervosa or binge-eating disorder who differ on the above parameters.nnnMETHODSnPlasma prolactin response to D-fenfluramine (30 mg p.o.) or placebo was measured in 58 drug-free female volunteers, comprising 15 underweight anorexic women, 18 bulimic women, 10 women with binge-eating disorder and 15 female healthy controls. Behavioural assessment included ratings of eating disorder symptoms, depression, aggression and food-related obsessions and compulsions.nnnRESULTSnA significantly decreased prolactin response to D-fenfluramine was found in underweight anorexic women and in bulimics with high frequency bingeing ( > 2 binge episodes/day), but not in patients with binge-eating disorder or in bulimics with low frequency bingeing (< I binge episode/day). In the whole bulimic group, a negative correlation emerged between frequency of bingeing and prolactin response. No significant correlation was found between physical or psychopathological measures and the hormonal response in any group.nnnCONCLUSIONSnThese results confirm our previous findings of an impaired serotonergic transmission in underweight anorexics and in bulimics with high frequency bingeing, but not in patients with less severe bulimia nervosa. Moreover, they show, for the first time, that the hypothalamic serotonergic system is not altered in women with binge-eating disorder.

Plasma prolactin response to D-fenfluramine is blunted in bulimic patients with frequent binge episodes.

BACKGROUNDnAbnormalities of brain serotonin (5-HT) transmission have been implicated in the pathophysiology of bulimia nervosa (BN), but no conclusive data have yet been provided. The purpose of this study was to assess 5-HT transmission via the measurement of the prolactin (PRL) response to the specific 5-HT releasing agent D-fenfluramine (D-FEN) in both patients with BN and comparison subjects.nnnMETHODSnAccording to a double-blind placebo-controlled design, plasma PRL response to D-FEN was measured in 14 drug-free bulimics and 14 matched healthy controls. In both patients and controls, eating-related psychopathology, depressive and obsessive-compulsive symptoms, and aggressiveness were measured by rating scales.nnnRESULTSnBaseline plasma levels of PRL and 17 beta-oestradiol were significantly reduced in bulimic patients, whereas basal plasma levels of cortisol did not significantly differ from healthy controls. PRL response to D-FEN was not different between patients and controls as groups, but it was significantly blunted in bulimics with high frequency bingeing (> or = 2 binge episodes per day; N = 7) as compared to both those with low frequency bingeing (< or = 1 binge episode per day; N = 7) and matched controls. A significant negative correlation emerged between the frequency of binge episodes and the hormone response to D-FEN. Moreover, although patients scored higher than healthy subjects on rating scales assessing depressive and obsessive-compulsive symptoms and aggressiveness, no significant correlation was found between these measures and the PRL response to D-FEN.nnnCONCLUSIONSnThese results support the idea that serotonin transmission is impaired in bulimic patients with frequent binge episodes.

Effect of chronic clozapine administration on [3H]MK801-binding sites in the rat brain: a side-preference action in cortical areas

We studied modifications in [3H]MK801-binding sites in the rat brain after chronic clozapine. We found a 20-30% reduction of [3H]MK801-binding sites in the anterior cingulate, frontoparietal motor and frontoparietal somatosensory cortices on the left side but none on the right. We also demonstrated a 20% bilateral increase of N-methyl-D-aspartate (NMDA) receptors in the dentate gyrus of the hippocampus. No changes were found in the prefrontal cortex, caudate-putamen, nucleus accumbens, hippocampus or olfactory tubercle.

Primary Prevention of Eating Disorders through Attitude Change: A Two Country Comparison

Primary prevention of eating disorders though increasing the knowledge base about eating disorders has been ineffectual, and in some cases has had a deleterious effect. The following study compared the efficacy of a classroom intervention using cognitive dissonance and repetition, in Italy and the U.S. In each country, health education classes of tenth grade students (U.S. n = 50, Italy n = 138) were randomly assigned to intervention and non-intervention sections. Subjects in the non-intervention sections received the standard health classes taught by their usual teacher. Students in the intervention sections received five classes taught by a psychologist (in the U.S.) or a psychiatrist (in Italy) specializing in eating disorders. Subjects in the intervention group also completed a cognitive dissonance essay designed to persuade a same sex friend that self-esteem should not be based solely on appearance. Intervention and non-intervention groups completed questionnaires before and after the intervention as well as at the end of the semester. The U.S. group had significantly higher Perfectionism scores and significantly lower Drive for Thinness scores (DT) than the Italian group. There was a significant decrease in DT for the intervention group in Italy. The intervention did not affect any other measures in the Italian group. There are clearly ethnic differences in comparing these two samples that may account for the baseline differences in eating attitudes. However, despite otherwise differing profiles, girls from each country had a desire to diet. This program appears to have made some impact in changing the attitudes away from a desire for thinness for Italian subjects. It is possible that many attitudes about weight, shape, and eating are established in this age group and a younger target audience would be more appropriate in the future.

Seasonal variation in plasma prolactin response to d-fenfluramine in healthy subjects

To assess dynamically a seasonal variation in the functioning of the central serotonin (5-HT) system, we investigated the prolactin (PRL) response to the specific serotonergic agent D-fenfluramine (D-FEN) in the different seasons of the year. Thirteen healthy women and 11 healthy men (six for each season), aged 20-50 years, received PO 30 mg D-FEN and placebo, according to a randomized double-blind design. As compared to placebo, D-FEN induced a clear-cut increase in plasma PRL levels in all the seasons; this response was higher in fall than in spring and summer (p < .01 and < .05, respectively). In all the subjects, as a group, the hormone response to the 5-HT probe was inversely correlated with the body weight and age. These results document a seasonal variability in the PRL response to D-FEN, which suggests a seasonal fluctuation in central 5-HT transmission in healthy humans.

Plasma prolactin response to d-fenfluramine in obsessive—compulsive patients before and after fluvoxamine treatment

The prolactin (PRL) responses to oral d-fenfluramine (30 mg) and placebo were assessed in 13 patients with obsessive-compulsive disorder (OCD) and in matched healthy subjects. After the neuroendocrine test, all patients were treated with fluvoxamine maleate (150-300 mg/day). At the end of the 10th week of treatment, 10 patients underwent again the neuroendocrine assessment. In drug-free patients, the PRL response to d-fenfluramine was significantly lower than in the comparison group. After 10-week fluvoxamine treatment, the PRL response to the serotonergic agent normalized. These findings suggest that, at least at the neuroendocrine level, central serotonergic responsivity is reduced in drug-free OCD patients, and that long-term fluvoxamine administration is associated with its normalization.

DIFFERENCES BETWEEN MORNING AND AFTERNOON HORMONAL RESPONSES TO D-FENFLURAMINE IN HEALTHY HUMANS

The prolactin (PRL) and cortisol responses to oral D-fenfluramine (30 mg) and placebo were measured in seven healthy subjects (two women and five men) in the morning and in the afternoon. As compared to placebo, D-fenfluramine significantly increased plasma PRL levels in both the morning and the afternoon, with no significant circadian difference. On the contrary, D-fenfluramine significantly enhanced plasma cortisol levels in the afternoon, but not in the morning. These data suggest that the time of the day at which the D-fenfluramine challenge test is carried out may be an important variable in determining the glucocorticoid response to the 5-HT releasing agent in humans.