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Biomedical subjects

Palmiero Monteleone

Publications and source records attributed to Palmiero Monteleone.

At least 19 recordsLinked to original sources
PubMed2007

The Leu72Met polymorphism of the ghrelin gene is significantly associated with binge eating disorder.

OBJECTIVES: The pathophysiological mechanisms underlying binge eating disorder are poorly understood. Evidence exists for the fact that abnormalities in peptides involved in the regulation of appetite, including ghrelin, may play a role in binge eating behavior. Genes involved in the ghrelin physiology may therefore contribute to the biological vulnerability to binge eating disorder. METHODS: We examined whether two polymorphisms of the ghrelin gene, the G152A (Arg51Gln) and C214A (Leu72Met), were associated with binge eating disorder. Ninety obese or nonobese women with binge eating disorder and 119 normal weight women were genotyped at the ghrelin gene. RESULTS: Statistical analyses showed that the Leu72Met ghrelin gene variant was significantly more frequent in binge eating disorder patients (chi2=5.940; d.f.=1, P=0.01) and was associated with a moderate, but significant risk to develop binge eating disorder (odds ratio=2.725, 95% confidence interval: 1.168-6.350). CONCLUSIONS: Although these data should be regarded as preliminary because of the small sample size, they suggest that the Leu72Met ghrelin gene variant may contribute to the genetic susceptibility to binge eating disorder.

Adult↗
PubMed2007

Aripiprazole in the treatment of schizophrenia: a consensus report produced by schizophrenia experts in Italy.

Schizophrenia is generally a chronic and disabling mental illness. Pharmacological therapy, which is used for relief of acute psychotic episodes and prevention of subsequent relapse, is essential for the effective management of schizophrenia. In order to alleviate the positive symptoms of schizophrenia, all antipsychotic agents act on the dopaminergic system. However, strong, high-affinity dopamine D(2)-receptor blockade may also be responsible for debilitating extrapyramidal symptoms (EPS) and hyperprolactinaemia. Unlike conventional antipsychotic agents, atypical antipsychotics also exert activity at other receptors, and it is generally acknowledged that, compared with conventional antipsychotics, atypical agents are associated with a broader spectrum of clinical efficacy and are better tolerated. However, other adverse effects such as weight gain and metabolic changes are cause for concern with some atypical antipsychotics. The novel atypical antipsychotic agent aripiprazole is a partial agonist at D(2) receptors that has been shown in clinical trials to be effective in treating both the positive and the negative symptoms of schizophrenia, and to be well tolerated, with a low propensity for EPS and no clinically significant weight gain, hyperprolactinaemia or corrected QT-interval prolongation. Aripiprazole thus provides clinicians with another treatment option, and in October 2005, schizophrenia experts participated in an expert consensus meeting that aimed to agree on a set of guidelines for best-practice use of aripiprazole in the acute and long-term management of schizophrenia in Italy. This report describes the outcome of the meeting. Our recommendations for dosage and administration of aripiprazole are in agreement with the manufacturer's prescribing information. Ideally, optimal dosing should be evaluated on an individual basis, taking into account patients' characteristics such as the presence or absence of agitation. Overall, in our experience, aripiprazole is generally a well accepted, well tolerated, safe and broadly effective first-line antipsychotic agent. Switching to aripiprazole from maintenance therapy with another antipsychotic also works well, provided the change is made gradually, involving tapering of the original medication.

Antipsychotic Agents↗
PubMed2006

The 196G/A (val66met) polymorphism of the BDNF gene is significantly associated with binge eating behavior in women with bulimia nervosa or binge eating disorder.

The brain-derived neurotrophic factor (BDNF) is involved not only in promoting neuronal outgrowth and differentiation, synaptic connectivity and neuronal repair, but also in modulating eating behavior. Since genetic factors likely contribute to the biological vulnerability to bulimia nervosa (BN) and binge eating disorder (BED), we investigated whether the functional 196G/A single nucleotide polymorphism (SNP) of the BDNF gene was associated to BN and/or BED or to some phenotypic aspects of the disordered eating. Two hundred and ten Caucasian women (126 with BN, 84 with BED and 121 healthy controls) participated into the study. No significant differences were found in the frequencies of the 196G/A variants of the BDNF gene among patients with BN or BED and healthy controls. In both BN and BED groups, subjects carrying the 196A/A genotype exhibited a weekly frequency of bingeing and a severity of binge eating (as assessed by the Bulimia Investigation Test Edinburgh) significantly higher than those with the 196A/G and 196G/G genotypes. These results suggest that the 196G/A SNP of the human BDNF gene does not contribute to the genetic susceptibility to BN and BED, but may predispose those patients to a more severe binge eating behavior.

Amino Acid Substitution↗
PubMed2006

Regulation, function, and dysregulation of endocannabinoids in models of adipose and beta-pancreatic cells and in obesity and hyperglycemia.

CONTEXT: Cannabinoid CB(1) receptor blockade decreases weight and hyperinsulinemia in obese animals and humans in a way greatly independent from food intake. OBJECTIVE: The objective of this study was to investigate the regulation and function of the endocannabinoid system in adipocytes and pancreatic beta-cells. DESIGN, SETTING, AND PATIENTS: Mouse 3T3-F442A adipocytes and rat insulinoma RIN-m5F beta-cells, pancreas and fat from mice with diet-induced obesity, visceral and sc fat from patients with body mass index equal to or greater than 30 kg/m(2), and serum from normoglycemic and type 2 diabetes patients were studied. MAIN OUTCOME MEASURE: Endocannabinoid enzyme and adipocyte protein expression, and endocannabinoid and insulin levels were measured. RESULTS: Endocannabinoids are present in adipocytes with levels peaking before differentiation, and in RIN-m5F beta-cells, where they are under the negative control of insulin. Chronic treatment of adipocytes with insulin is accompanied by permanently elevated endocannabinoid signaling, whereas culturing of RIN-m5F beta-cells in high glucose transforms insulin down-regulation of endocannabinoid levels into up-regulation. Epididymal fat and pancreas from mice with diet-induced obesity contain higher endocannabinoid levels than lean mice. Patients with obesity or hyperglycemia caused by type 2 diabetes exhibit higher concentrations of endocannabinoids in visceral fat or serum, respectively, than the corresponding controls. CB(1) receptor stimulation increases lipid droplets and decreases adiponectin expression in adipocytes, and it increases intracellular calcium and insulin release in RIN-m5F beta-cells kept in high glucose. CONCLUSIONS: Peripheral endocannabinoid overactivity might explain why CB(1) blockers cause weight-loss independent reduction of lipogenesis, of hypoadiponectinemia, and of hyperinsulinemia in obese animals and humans.

3T3 Cells↗
PubMed2006

No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene with anorexia nervosa or bulimia nervosa.

Genetic factors likely contribute to the biological vulnerability to anorexia nervosa (AN) and bulimia nervosa (BN). We investigated whether the Arg51Gln and/or the Leu72Met gene polymorphisms of the human ghrelin, a peptide involved in the regulation of eating behavior, were associated to AN and/or BN. Two-hundred-ninety-two Caucasian women (114 with BN, 59 with AN and 119 healthy controls) participated into the study. No significant differences were found in the frequencies of the Arg51Gln and the Leu72Met ghrelin gene variants among patients with AN or BN and healthy controls. Moreover, no significant differences emerged in eating-related phenotypic variables between patients carrying the Leu72Met genotype as compared to those with the Leu72Leu genotype. These results suggest that the Arg51Gln and the Leu72Met polymorphisms of the human ghrelin gene do not contribute to the genetic susceptibility to AN and BN.

Adolescent↗
PubMed2006

Association of a functional serotonin transporter gene polymorphism with binge eating disorder.

The pathophysiological mechanisms underlying binge eating disorder (BED) are poorly understood. There is evidence that abnormalities in brain serotonin (5HT) play an important role in binge eating behavior, therefore genes involved in 5HT transmission, such as the 5HT transporter (5HTT) gene, may contribute to the biological vulnerability to BED. We examined whether the polymorphism of the promoter of the 5HTT gene, consisting of a long (L) and a short (S) variant, was associated with BED. Seventy-seven obese or non-obese women with BED, and 61 normal weight control women were genotyped at the 5HTT gene linked polymorphism (5HTTLPR). Statistical analysis showed that both the LL genotype and the L allele of the 5HTTLPR were significantly more frequent in BED subjects. Moreover, the L allele was associated with a moderate but significant risk to develop BED (OR = 2.01, CI = 1.33-3.57). Although these data should be regarded as preliminary because of the small size of our sample, they suggest that the 5HTTPRL may contribute to the genetic susceptibility to BED.

Adult↗
PubMed2005

Impaired reduction of enhanced levels of dehydroepiandrosterone by oral dexamethasone in anorexia nervosa.

Allopregnanolone and dehydroepiendrosterone (DHEA) have been supposed to be involved in some psychiatric disorders including anorexia nervosa (AN). The secretion of DHEA and allopregnanolone occurs in both the brain and the adrenal gland, where it is under the control of the corticotrophin-releasing factor (CRF)/adrenocorticotrophin hormone (ACTH) system, and, according to the increased CRF/ACTH drive found in AN, we previously reported enhanced morning levels of both DHEA and allopregnanolone in underweight anorexic patients. To further characterize the physiology of these neurosteroids in AN, we measured plasma levels of cortisol, DHEA and allopregnanolone after the oral administration of 1 mg dexamethasone at 800h in six underweight AN women and ten age-matched healthy females. We found that, before dexamethasone administration, both cortisol and DHEA plasma concentrations were significantly increased in anorexic patients as compared to controls, whereas plasma allopregnanolone levels although increased in the former did not reach a statistical significance. Moreover, while cortisol levels after dexamethasone administration were suppressed in AN to values similar to normal controls, DHEA concentrations, although significantly decreased, remained higher than in normal controls. These data support the view that in AN, the increased production of DHEA may be linked to mechanisms other than the enhanced CRF/ACTH drive.

Adult↗
PubMed2005

Enhanced serum cholesterol and triglyceride levels in bulimia nervosa: relationships to psychiatric comorbidity, psychopathology and hormonal variables.

Increased levels of cholesterol have been reported in patients with bulimia nervosa (BN), but all but one of the published studies were performed on non-fasting subjects, which limits the interpretation of this finding. Moreover, the relationships between serum lipids and comorbid psychiatric disorders or bulimic psychopathology have scarcely been investigated. We measured serum levels of total cholesterol, triglycerides, glucose, 17beta-estradiol and thyroid hormones in 75 bulimic women and 64 age-matched healthy females after an overnight fast. Compared with healthy women, bulimic patients exhibited significantly enhanced serum levels of cholesterol and triglycerides, but similar values of glucose, 17beta-estradiol, FT3 and FT4. No significant differences emerged in these variables between patients with or without comorbid depression, borderline personality disorder or lifetime anorexia nervosa. Circulating cholesterol was positively correlated to the patients' drive for thinness, ineffectiveness, enteroceptive awareness and impulse regulation sub-item scores of the Eating Disorder Inventory-2. These findings confirm that BN is associated with increased levels of serum lipids. This alteration may be involved in the pathophysiology of certain psychopathological characteristics of BN and cannot be explained by the co-occurrence of other psychiatric disorders.

Adult↗
PubMed2005

Investigation of peptide YY and ghrelin responses to a test meal in bulimia nervosa.

BACKGROUND: Gut-derived peptides, such as peptide YY (PYY) and ghrelin that regulate the initiation and termination of meals, could play a role in the altered eating behavior of patients with bulimia nervosa (BN). Therefore, we aimed to assess plasma PYY and ghrelin responses to a test meal in symptomatic bulimics. METHODS: Ten healthy women and nine women with BN underwent blood sample collections before and after the ingestion of a test meal of 1300 Kcal (with 15% carbohydrates, 10% proteins, and 75% fat) at 12:00 noon. Plasma total PYY, ghrelin, insulin, and glucose were assayed. RESULTS: As compared with healthy women, bulimics exhibited a significantly blunted increase of circulating PYY (p < .007) and a significantly reduced suppression of plasma ghrelin (p < .0004) after the test meal. No significant differences emerged in food-induced plasma insulin and glucose changes between the two groups. Plasma ghrelin suppression after the meal was significantly correlated with plasma PYY increase. CONCLUSIONS: We replicated our previous findings of an altered ghrelin response to food ingestion in people with BN and showed for the first time a blunted PYY increase after food consumption in these patients. These findings support the occurrence in BN of a profound dysregulation of some peripheral regulatory mechanisms involved in the short-term regulation of feeding behavior that might be involved in the pathophysiology of their binge eating behavior.

Adult↗
PubMed2005

Circulating ghrelin is decreased in non-obese and obese women with binge eating disorder as well as in obese non-binge eating women, but not in patients with bulimia nervosa.

Ghrelin is a peripheral gastric peptide involved in the regulation of eating behavior and energy homeostasis. While changes in ghrelin plasma levels have been found in anorexia nervosa, bulimia nervosa (BN) and obesity, no study has assessed circulating ghrelin in binge eating disorder (BED). Therefore, we measured plasma levels of this peptide in women with BED as compared to women with BN, obesity and healthy controls. One hundred and eighty-two drug-free women (56 bulimics, 13 non-obese and 34 obese BED subjects, 28 obese non-binge eating women and 51 non-obese healthy women) underwent psychopathological and nutritional assessments and blood sample collection for glucose and ghrelin assays in the morning. As compared to non-obese healthy women, both non-obese and obese BED women as well as obese non-binge eating women had significantly increased values of body weight, body mass index and body fat mass. Moreover, plasma ghrelin concentrations were significantly decreased in both non-obese (P<0.01) and obese (P<0.0001) BED women as well as in obese non-binge eating women (P<0.001) but not in women with BN. No significant correlations emerged between plasma ghrelin values and the frequency of binge/vomiting in BN subjects or the frequency of bingeing in BED individuals. The reduction of plasma ghrelin in non-obese and obese binge eaters as well as in obese non-binge eaters may represent a secondary change aiming to counteract their positive energy imbalance.

Adult↗
PubMed2005

Circulating brain-derived neurotrophic factor is decreased in women with anorexia and bulimia nervosa but not in women with binge-eating disorder: relationships to co-morbid depression, psychopathology and hormonal variables.

BACKGROUND: Several lines of evidence indicate a role of the brain-derived neurotrophic factor (BDNF) in the modulation of eating behaviour. Therefore, alterations in the physiology of this neurotrophin may be involved in the pathogenesis of eating disorders. In the present study, we investigated serum levels of BDNF in patients with anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED). METHOD: Ninety-nine drug-free women (27 with AN, 24 with BN, 24 with BED and 24 healthy controls) underwent both a blood sample collection in the morning and diagnostic and psychopathological assessments by means of structured clinical interviews and ad-hoc rating scales. Serum levels of BDNF, 17 beta-oestradiol, FT3 and FT4 were measured. RESULTS: Compared to healthy controls, serum levels of BDNF were significantly reduced in underweight AN women and in normal weight BN women, but not in overweight BED women. Changes in circulating BDNF levels were not affected by the presence of co-morbid depressive disorders. No significant correlation emerged between neurotrophin concentrations and psychopathological, nutritional, demographic and hormonal variables. CONCLUSIONS: These findings evidentiate alterations in serum BDNF levels in malnourished patients with AN or BN, but not in well-nourished individuals with BED. Since BDNF seems to exert a satiety effect, its reduction may represent an adaptive change to counteract the decreased calorie ingestion of AN and BN individuals.

Adult↗
PubMed2005

Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa.

The endocannabinoid system, consisting of two cannabinoid receptors (CB1 and CB2) and the endogenous ligands anandamide (arachidonoylethanolamide (AEA)) and 2-arachidonoylglycerol (2-AG), has been shown to control food intake in both animals and humans, modulating either rewarding or quantitative aspects of the eating behavior. Moreover, hypothalamic endocannabinoids seem to be part of neural circuitry involved in the modulating effects of leptin on energy homeostasis. Therefore, alterations of the endocannabinoid system could be involved in the pathophysiology of eating disorders, where a deranged leptin signalling has been also reported. In order to verify this hypothesis, we measured plasma levels of AEA, 2-AG, and leptin in 15 women with anorexia nervosa (AN), 12 women with bulimia nervosa (BN), 11 women with binge-eating disorder (BED), and 15 healthy women. Plasma levels of AEA resulted significantly enhanced in both anorexic and BED women, but not in bulimic patients. No significant change occurred in the plasma levels of 2-AG in all the patients' groups. Moreover, circulating AEA levels were significantly and inversely correlated with plasma leptin concentrations in both healthy controls and anorexic women. These findings show for the first time a derangement in the production of the endogenous cannabinoid AEA in drug-free symptomatic women with AN or with BED. Although the pathophysiological significance of this alteration awaits further studies to be clarified, it suggests a possible involvement of AEA in the mediation of the rewarding aspects of the aberrant eating behaviors occurring in AN and BED.

Adult↗
PubMed2004

Leptin functioning in eating disorders.

Leptin is an adipocyte-derived hormone, which is involved predominantly in the long-term regulation of body weight and energy balance by acting as a hunger suppressant signal to the brain. Leptin is also involved in the modulation of reproduction, immune function, physical activity, and some endogenous endocrine axes. Since anorexia nervosa (AN) and bulimia nervosa (BN) are characterized by abnormal eating behaviors, dysregulation of endogenous endocrine axes, alterations of reproductive and immune functions, and increased physical activity, extensive research has been carried out in the last decade in order to ascertain a role of this hormone in the pathophysiology of these syndromes. In this article, we review the available data on leptin physiology in patients with eating disorders. These data support the idea that leptin is not directly involved in the etiology of AN or BN. However, malnutrition-induced alterations in its physiology may contribute to the genesis and/or the maintenance of some clinical manifestations of AN and BN and may have an impact on the prognosis of AN.

Adipose Tissue↗
PubMed2004

Long-term treatment with clozapine does not affect morning circulating levels of allopregnanolone and THDOC in patients with schizophrenia: a preliminary study.

Clozapine has been shown to acutely increase the rat brain and plasma concentrations of the neuroactive steroids 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP) or allopregnanolone and THDOC, 2 positive allosteric modulators of GABA-A receptors. Hence, it has been suggested that this effect could underlie the therapeutic efficacy of this drug, contributing to its atypical profile. So far, no study assessed whether the effects on neurosteroids reported in the experimental animal occur also in humans. Therefore, we measured plasma levels of 3alpha,5alpha-THP and THDOC in a sample of drug-resistant schizophrenic patients before and after 1, 2, 4, 6, 8, 12, and 24 weeks of clozapine administration (600 mg/d by the end of the 6th week). No significant changes in circulating concentrations of 3alpha,5alpha-THP and THDOC were observed in the course of clozapine administration in spite of the patients' good clinical response to the drug. These findings provide evidence, for the first time, that clozapine is not able to affect morning circulating levels of 3alpha,5alpha-THP and THDOC in humans. Therefore, although we cannot exclude that changes in neuroactive steroids could occur immediately after the daily administration of clozapine as in the experimental animal, our data support the view that the therapeutic efficacy of this atypical antipsychotic is not linked to changes in the baseline concentrations of peripheral 3alpha,5alpha-THP and THDOC.

Adult↗
PubMed2003

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'.

Adult↗
PubMed2003

Neurocognitive functioning in subjects with eating disorders: the influence of neuroactive steroids.

BACKGROUND: Neuropsychological studies in subjects with eating disorders (EDs) have reported conflicting findings, which might be accounted for by several confounding variables, including neuroendocrine changes. METHODS: General abilities, executive functions, attention, and noneffortful learning were assessed in 45 patients with EDs and 45 healthy comparison subjects (HCS). Plasma levels of 17beta-estradiol, cortisol, allopregnanolone, dehydroepiandrosterone and its sulfate metabolite (DHEA and DHEAS) were evaluated in a subsample of patients and HCS. The influence of clinical, demographic, and neuroendocrine variables on neurocognitive performance was explored. RESULTS: Patients were slower than HCS on noneffortful learning and more accurate on a spatial executive task. DHEA and DHEAS were increased and positively correlated with accuracy on the executive task, while cortisol positively correlated with speed of noneffortful learning. CONCLUSIONS: A subtle impairment of noneffortful learning is the only neuropsychological deficit in patients with EDs. Changes in neuroactive steroids influence neurocognitive performance.

Adolescent↗