Serotonin transporter polymorphism and potential response to SSRIs in bulimia nervosa.
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Biomedical subjects
Publications and source records attributed to P Monteleone.
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OBJECTIVE: The aim of the present study was to evaluate the clinical usefulness of routine use of endometrial ultrasound in asymptomatic, bleeding-free postmenopausal women. METHODS: We retrospectively reviewed the data of 850 postmenopausal women subjected to hysteroscopy, focusing our attention on those cases (148) with an ultrasound indication of endometrial thickening. RESULTS: In 850 postmenopausal women, we identified 27 (3.2%) endometrial adenocarcinomas. In these subjects, the indication for office hysteroscopy was abnormal uterine bleeding in 24 (24/27; 88.9%) cases; pathological pap smear with abnormal endometrial cells in 2 (2/27; 7.4%) cases and thickened endometrium upon transvaginal ultrasound (tvUS) only in one (1/27; 3.7%) patient. On the other hand, 148 hysteroscopies were performed on the basis of the tvUS indication in otherwise asymptomatic (bleeding free) postmenopausal women; only 1(0.7%) of these presented an adenocarcinoma. CONCLUSION: Our findings show that the use of tvUS as a screening tool for endometrial pathology in asymptomatic postmenopausal women generates 93.2% false positive results, so that most of these women undergo this second level invasive procedure uselessly. Our data suggest that, in asymptomatic postmenopausal women, endometrial ultrasound evaluation is not worthwhile as a screening tool, such as it is considered in common clinical practice. The present results call for a larger prospective trial to further elucidate this controversial issue.
BACKGROUND: Immune function is altered in adult depressed patients. The aim of our study was to see whether or not cytokine secretion is impaired at a very young phase of development of depressive disorders, possibly being pathogenetically involved in their course. METHODS: Basal plasma concentrations of interleukin-1beta (Il-1beta) and tumor necrosis factor-alpha (TNF-alpha) were measured radioimmunologically in 22 drug-free children-adolescents, 11 with recurrent major depressive disorders (MDD) and 11 with dysthymia (DYS), and in 11 psychophysically healthy age-sex matched controls. Depression was monitored using the Poznanski Rating Scale and Anxiety with the Reynold Rating Scale. RESULTS: Il-1beta levels were not significantly different in MDD from controls and significantly higher than normal in DYS subjects. TNF-alpha levels were not significantly different in MDD patients from controls and significantly lower than normal in DYS patients. Cytokine concentrations were correlated with anxious and depressive symptomatology in MDD but not in DYS patients. CONCLUSIONS: There is a cytokine pathology in depressive disorders of obscure etiopathogenetical significance.
Malnutrition and absence of exogenous luminal nutrients in the gastrointestinal tract affect intestinal permeability (IP) leading to an increased penetration of substances that passively cross intestinal epithelium via intercellular pathways. We hypothesised that an increase in IP could occur in patients with anorexia nervosa because of their prolonged fasting and chronic malnutrition. Therefore, we assessed IP in 14 drug-free anorexic women and 19 drug-free age-matched healthy women by means of the lactulose/mannitol (LA/MA) test. To this purpose, after an overnight fast, subjects ingested an oral solution containing 5 g lactulose and 2 g mannitol in 100 ml water. Urine specimens were collected immediately before and 30, 60, 120, 180, 240 and 300 min after the ingestion of the sugar solution. Urinary lactulose and mannitol were determined by high-performance anion exchange chromatography coupled with pulsed amperometric detection. We found that IP, as expressed by the 5-h LA/MA excretion ratio, was significantly decreased in anorexic women because of a lower urinary recovery of lactulose. Moreover, in patients, the time course of lactulose excretion significantly differs from healthy controls. These results do not confirm our hypothesis of increased IP in anorexia nervosa. Since IP reflects the anatomo-functional status of intestinal mucosa, the present findings support the idea that changes in the anatomo-physiology of intestinal mucosa occur in anorexia nervosa.
Tibolone, a steroid with tissue-specific activities, can reduce the bone resorption that takes place after the menopause. The present calcium-controlled, 2-year study aimed to evaluate the effect of two doses of oral tibolone, 1.25 mg and 2.5 mg, on bone loss in early postmenopausal women. The subjects were randomly allocated to one of the three groups, namely tibolone 2.5 mg (n = 30), tibolone 1.25 mg (n = 30) and a control group (n = 30). All subjects received 1000 mg of calcium per day. In the control group, vertebral and femur bone mineral density (BMD) decreased significantly (p < 0.05) after 12 and 24 months. In both tibolone groups, vertebral and femur BMD increased significantly (p < 0.05) increased after 12 and 24 months. In the control group, bone turnover markers (urinary excretion of hydroxyproline/creatinine and plasma osteocalcin levels) remained constant, while in both tibolone groups these markers showed similar significant decreases (p < 0.05) after 12 and 24 months. After 24 months, body weight increased in the control group (p < 0.05), while smaller increments were evident in the tibolone groups. Symptom scores in the control group did not show any significant modification during the study. In contrast, the administration of 2.5 mg tibolone was significantly (p < 0.05) effective in reducing hot flushes and other symptoms. The tibolone 1.25 mg group yielded similar results (even if it was proportionally less efficient) to the higher dose. It is concluded that tibolone is effective, even at lower doses, in relieving climacteric symptoms and preventing a decrease in spine and femur BMD in early postmenopausal women.
Several studies have been performed during recent years to investigate the existence of a possible endocrine cause for premenstrual syndrome (PMS); the results reported are often discordant. Great interest has been raised around allopregnanolone, which could be involved in the determination of mood disorders reported by PMS patients. During the luteal phase, lower levels of this hormone have been detected in PMS patients. The aim of our study was to evaluate estradiol, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, total and free testosterone, cortisol, pregnenolone and allopregnanolone levels in 20 patients suffering from PMS and to compare them with those found in 20 fertile healthy women in the follicular and the luteal phases. Adrenocorticotropic hormone (ACTH) tests after dexamethasone suppression were performed in 10 patients of each group during the follicular and the luteal phases. In the PMS group, significantly lower allopregnolone levels were found in the luteal phase, while progesterone was lower in the PMS group in both phases. In the PMS group, higher free testosterone levels were found during the luteal phase and higher DHEA levels in both the follicular and the luteal phases. The present data confirm reduced allopregnanolone levels in the luteal phase in PMS patients, together with higher levels of DHEA and free testosterone. It is possible to conclude that, in addition to the previously described reduced luteal secretion of allopregnanolone, the adrenal gland production of this steroid in PMS sufferers is also impaired in the luteal phase. Considering the specific actions of these hormones on the control of mood and behavior, this specific hormonal milieu may contribute to the cyclic occurrence of anxiety, aggressiveness and irritability reported by PMS patients.
Sex-steroid-related tumours in women are represented by breast cancer and endometrial cancer, but a possible relationship may exist between sex steroids and both ovarian and colon cancer. Unopposed oestrogen therapy is known to increase the risk of endometrial cancer and is appropriate only for hysterectomized women. In women with an intact uterus, an appropriate combination of oestrogen and progestin does not appear to increase-and may even decrease-the risk of endometrial cancer. Current users of HRT seem to benefit from a reduced risk for colon cancer. As for epithelial ovarian cancer, the present data are very conflicting. The association between replacement hormones and this malignancy seems to be stronger for unopposed oestrogen than for oestrogen-progestin treatment. Data available at the moment do not allow discriminating for dose, routes of administration, bioavailability and tissue effects of different compounds so that it is inappropriate to consider all forms of HRT jointly. The future of HRT in post-menopausal women lies in the individualization of the therapy based upon personal risk factors and characteristics.
BACKGROUND: Ghrelin and leptin are endogenous peripheral proteins involved in the regulation of eating behaviour. In particular, ghrelin stimulates hunger and promotes food ingestion, whereas leptin increases satiety and reduces food consumption. Therefore, alterations in the physiology of these peptides may play a role in the pathogenesis of eating disorders such as bulimia nervosa. In the present study, we investigated ghrelin and leptin responses to food ingestion in patients with bulimia nervosa. METHOD: Nine symptomatic drug-free bulimic women and 12 age-matched healthy women ingested a meal of 1207 kcal (60% carbohydrates, 23% fat and 17% proteins) at 12.00 a.m. and underwent blood sample collection before and 45, 60, 90, 120 and 180 min after the meal. Plasma levels of ghrelin, leptin, insulin and glucose were measured. RESULTS: In healthy women, circulating ghrelin exhibited a drastic decrease after the food intake whereas, in bulimic patients, this response was significantly blunted. No difference between the two subjects groups was observed in post-prandial profiles of plasma leptin, insulin and glucose. CONCLUSIONS: The lack of a leptin response to food ingestion, in both bulimic and healthy women, is compatible with the role of this peptide as long-term rather than short-term modulator of eating behaviour. The blunted ghrelin response to food ingestion may support the occurrence in bulimic subjects of an impaired suppression of the drive to eat following a meal. This may have implications for binge-eating.
Alterations of cellular G proteins have been implicated in the pathophysiology of some psychiatric disorders. So far, no study assessed G protein function in anorexia nervosa (AN) and bulimia nervosa (BN). Therefore, we measured immunoreactive levels of G(alpha s), G(alpha i), G(alpha q/11) and G(beta) protein subunits in mononuclear leukocytes of 71 drug-free women, including 25 subjects with AN, 26 individuals with BN and 20 healthy controls. As compared to healthy women, anorexic patients exhibited significantly increased levels of G(alpha i) and G(beta) proteins, while bulimic patients had significantly increased levels of G(alpha s), G(alpha i) and G(beta) proteins. Immunoreactive levels of peripheral G protein subunits were not significantly correlated with demographic or nutritional parameters. These findings, although obtained in peripheral blood cells, may suggest a derangement of G protein-mediated signal transduction in the pathophysiology of eating disorders.
OBJECTIVES: The aim of this cross-sectional study was to describe QoL in a large sample of women attending menopause centres and compare untreated postmenopausal women and matched HRT users by employing the Women's Health Questionnaire (WHQ) and two generic instruments, the SF-36 and the EQ-5D. METHODS: Overall, 2906 women were recruited by 64 menopause centres throughout Italy, of whom 2160 filled in the questionnaire (1093 on HRT and 1067 not on HRT; response rate: 74%). RESULTS: HRT users tended to be younger, healthier and with shorter menopause duration as opposed to non users, while no major socio-economic differences were present. At multivariate analysis, the presence of chronic diseases, low socio-economic status and living in Southern Italy represented the most important predictors of poor QoL. Furthermore, HRT users showed a lower probability of reporting problems in usual activities and pain/discomfort (EQ-5D), role limitations due to emotional problems (SF-36) and anxiety/fears (WHQ). HRT users also showed highly significant better outcomes in those areas that are more directly attributable to hormonal changes of mid age, namely vasomotor symptoms and sexual problems. CONCLUSIONS: Although QoL is mainly influenced by socio-economic and cultural factors, HRT has the potential for improving not only symptoms, but also more general aspects of physical and psychological well-being of symptomatic postmenopausal women.
Leptin is thought to modulate feeding behaviour, body weight and energy metabolism by acting through specific cellular receptors. Derangements of leptin production have been repeatedly reported in patients with anorexia nervosa (AN) or bulimia nervosa (BN), but no information has been provided on the functional status of leptin receptors in these disorders. Therefore, we measured plasma levels of leptin and its soluble receptor (Ob-Re) in a total of 130 women, including 22 patients with AN, 45 patients with BN, 18 patients with the binge-eating disorder (BED), 12 non-binge eating obese women and 33 healthy women. Circulating leptin was drastically reduced in underweight anorexics and normal-weight bulimics, but increased in overweight BED patients and non-binge-eating obese women. Conversely, plasma levels of Ob-Re were significantly increased in patients with AN or BN, but decreased in BED and non-binge-eating obese women. Significant inverse correlations were detected between plasma levels of leptin and those of Ob-Re in all the subject groups, except in non-binge-eating obese subjects. These results show, for the first time, that opposite modifications occur in circulating levels of leptin and Ob-Re across the eating-disorder spectrum. The relevance of these findings to the pathophysiology and treatment of eating disorders remains to be elucidated.
OBJECTIVES: The Women's Health Questionnaire has been developed and validated in Anglo-Saxon and Swedish populations. The purpose of this study was to evaluate the Italian version of the questionnaire to determine whether cross-cultural differences exist in the perception of quality of life, and to use it to compare the quality of life in women attending menopause centers with that of women in the general population. METHODS: An Italian version of the Women's Health Questionnaire (WHQ) was produced, using the forward-backward translation method to ensure conceptual equivalence, and approved by the originator. Women were recruited by random selection from the general population and from menopause centers, those taking hormone replacement therapy being ineligible. The questionnaire was completed anonymously at home and mailed to the co-ordinating center. Psychometric evaluation included tests of item convergent and discriminant validity, internal-consistency reliability, test-retest reliability, construct validity and the discriminative properties of the questionnaire. RESULTS: The completeness of the data was good, with missing-value rates consistently low for most items. Item-scale correlations, used to evaluate internal consistency, were also good and the scaling success rate, used to measure item discriminant validity, was high for all scales. Scale scores were reliable for seven out of nine scales and test-retest reliability was excellent. There were few significant differences between the two populations of women in most of the WHQ areas. A comparison of Italian data with published data on English women showed great similarity. CONCLUSION: The Italian version of the WHO is valid and reproducible. The subjective perception of the menopause and its related problems is similar in geographically and culturally different populations.
Hormone replacement therapy (HRT) is considered the mainstay for postmenopausal osteoporosis prevention. However, at the standard doses, HRT preparations can induce bothersome hormone-related side-effects, in both sequential and continuous combined regimens. Lower-dose HRT schedules are reported to be highly effective in the relief of climacteric symptoms, inducing minimal endometrial stimulation with very low rates of unscheduled bleeding. Moreover, low-dose HRT associated with an adequate calcium supplement can spare bone by preventing the increase in bone turnover and the resultant bone loss in postmenopausal women. Low-dose regimens may be considered as a starting dose not only in elderly subjects, but also in early postmenopausal women to allow for adjustment to HRT. In older women, these may minimize the occurrence of side-effects and improve compliance, while preventing the long-term consequences of estrogen deprivation.
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The aim of this study was to examine whether anorexia and bulimia nervosa are accompanied by lower serum activity of prolyl endopeptidase (PEP;EC 3.4.21.26; post-proline cleaving enzyme), a cytosolic endopeptidase which cleaves peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass. Substrates of PEP are, amongst others, neuroactive peptides, such as arginine vasopressin, luteinizing hormone-releasing hormone, thyrotropin releasing hormone,alpha-melanocyte secreting hormone, substance P, oxytocin, bradykinin, neurotensin and angiotensin (Ag) I and II. Serum PEP activity was measured in the serum of 18 normal women, 21 anorexia nervosa and 21 bulimia nervosa women by means of a fluoremetric method. The Bulimic Investigatory Test, Edinburgh (BITE), the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale (HDRS) were scored. Serum PEP activity was significantly lower in patients with bulimia nervosa and anorexia nervosa, irrespective of the restricted or binging subtype, than in normal controls. There were significant and inverse correlations between serum PEP activity and the HDRS and BITE. In anorectic patients, but not in normal or bulimic patients, there was a significant correlation between serum PEP and body mass index. In bulimic patients, but not in normal or anorectic patients, there was a significant correlation between serum PEP and duration of illness. It is concluded that lowered serum PEP activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesized that a combined dysregulation of PEP and neuroactive peptides, which are substrates of PEP, could be an integral component of eating disorders.
PURPOSE: Several lines of evidence indicate that there exists a relation between ovarian hormones and epilepsy. Estrogens decrease seizure threshold and increase brain excitability, whereas progesterone has an inhibitory effect and reduces epileptiform activity. Recently considerable interest has turned to neuroactive steroids, a group of progesterone metabolites, as endogenous modulators of excitability of the central nervous system (CNS). Their ability to alter neuronal firing rapidly occurs through interaction with gamma-aminobutyric acid (GABA) A receptor complex. In a previous experience, serum allopregnanolone (3alpha-OH-5alpha-pregnan-20-one) levels were measured in 15 women with partial epilepsy in the intercritical phase, and no significant differences were found between patients and control subjects. METHODS: To find out if there are changes in serum allopregnanolone levels after epileptic seizure, blood samples were drawn immediately, 15 min, and 6 h after a seizure in seven fertile females with partial epilepsy. RESULTS: The most interesting finding is that allopregnanolone increases in serum during the first 15 min after partial seizures (p < 0.05) and decreases after 6 h. CONCLUSIONS: These data are consistent with a role for allopregnanolone in the control of neuronal excitability and seizures.
Peripheral amino acid changes have been reported in schizophrenia, but results are not consistent. We measured serum levels of different amino acids in 11 neuroleptic-resistant schizophrenic patients before and after clozapine treatment and in 11 age- and sex-matched healthy subjects. The schizophrenic patients exhibited significantly higher levels of serum aspartate, glutamate, isoleucine, histidine and tyrosine and significantly lower concentrations of serum asparagine, tryptophan and serine. In patients, the ratio between tryptophan and large neutral amino acids (LNAA) was significantly lower than in matched controls, whereas the tyrosine/LNAA ratio did not differ significantly. Moreover, 12 weeks of clozapine administration significantly reduced serum levels of glutamate but did not restore the values observed in normal controls, nor did it affect other amino acid concentrations. These data show changes in serum amino acids that may influence central serotonergic, dopaminergic and glutamatergic transmission in neuroleptic-resistant schizophrenics.
A decreased production of leptin has been reported in women with anorexia nervosa (AN) and has been attributed merely to the patients' reduced body fat mass. The extent to which eating patterns, purging behaviors, psychopathology and endocrine changes may contribute to the genesis of leptin alterations has not been deeply investigated. Therefore, we measured plasma levels of leptin, glucose and other hormones in three groups of eating disorder patients with different body weight (BW), eating patterns and purging behaviors. Sixty-seven women, 21 with AN, 32 with bulimia nervosa (BN), 14 with binge-eating disorder (BED) and 25 healthy females volunteered for the study. We found that circulating leptin was significantly reduced in AN and BN patients, but significantly enhanced in women with BED. In anorexics, plasma glucose was decreased, whereas plasma cortisol was enhanced; blood concentrations of 17beta-estradiol and prolactin (PRL) were reduced in both AN, BN and BED patients. In all subject groups, a strong positive correlation emerged between plasma levels of leptin and the subjects' BW or body mass index, but not between leptin and psychopathological measures, plasma glucose, cortisol, PRL and 17beta-estradiol. Since leptin was reduced in both underweight anorexics and normal weight bulimics, but increased in overweight BED women, who compulsively binge without engaging in compensatory behaviors, we suggest that factors other than BW may play a role in the determination of leptin changes in eating disorders.