Antonio Fuschino

Opposite Changes in the Serum Brain-Derived Neurotrophic Factor in Anorexia Nervosa and Obesity

Objective: A role for the brain-derived neurotrophic factor (BDNF) in the regulation of eating behavior has been recently demonstrated. Therefore, the possibility exists that alterations in BDNF production and/or activity are involved in the pathophysiology of anorexia nervosa (AN) and obesity. Methods: We measured morning serum levels of BDNF in 22 women with AN, 24 women with obesity (body mass index [BMI] > 30 kg/m2), and 27 nonobese healthy women. All the subjects were drug-free and underwent a clinical assessment by means of rating scales measuring both eating-related psychopathology and depressive symptoms. Results: As compared with the nonobese healthy controls, circulating BDNF was significantly reduced in AN patients and significantly increased in obese subjects. No significant difference was observed in serum BDNF concentrations between AN women with or without a comorbid depressive disorder. Moreover, serum BDNF levels were significantly and positively correlated with the subjects’ body weight and BMI. Conclusion: The BDNF changes observed in AN and obesity are likely secondary adaptive mechanisms aimed at counteracting the change in energy balance that occurs in these syndromes. AN = anorexia nervosa; BW = body weight; BDNF = brain-derived neurotrophic factor; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; SCID-I = Structured Clinical Interview for DSM-IV Axis 1 Disorders; BMI = body mass index; MINI = Mini International Neuropsychiatric Interview; EDI = Eating Disorder Inventory; BITE = Bulimic Investigation Test Edinburgh; MADRS = Montgomery-Asberg Depression Rating Scale; ANOVA = analysis of variance; 5-HT = serotonin.

Opposite modifications in circulating leptin and soluble leptin receptor across the eating disorder spectrum

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.

Investigation of the serotonin transporter regulatory region polymorphism in bulimia nervosa: relationships to harm avoidance, nutritional parameters, and psychiatric comorbidity.

Objective: Genes involved in 5HT transmission have been supposed to contribute to the biologic vulnerability for bulimia nervosa (BN). Because a long (L) and a short (S) variant of the promoter region of the 5HT transporter gene have been identified, we tested whether the 5HTT gene-linked polymorphic region (5HTTLPR) could represent a susceptibility factor for BN and/or could be related to nutritional parameters, harm avoidance personality dimension, and psychiatric comorbidity. Methods: A total of 219 white women (125 bulimics and 94 healthy control subjects) underwent a blood sample collection for 5HTTLPR genotyping and a clinical evaluation assessing comorbidity for axis I and II psychiatric disorders, harm avoidance personality dimension, and body composition (only patients). Results: The distribution of the 5HTTLPR genotypes did not significantly differ between patients and control subjects, although the L allele was significantly more frequent in the former. Bulimic individuals carrying at least one copy of the S allele had significantly lower mean body mass index and body fat mass values and significantly higher mean harm avoidance score than patients with the LL genotype. No significant association was found between the 5HTTLPR genotype and comorbid axis I and II psychiatric disorders. Conclusions: These findings support the view that polymorphic variants of the 5HTT promoter region do not play a part in predisposing to BN, whereas they seem to predispose bulimic individuals to nutritional impairment and increased harm avoidance. ANOVA = analysis of variance; BMI = body mass index; BW = body weight; BN = bulimia nervosa; MINI = Mini International Neuropsychiatric Interview; NS = not significant; 5HT = serotonin; 5HTT = serotonin transporter; 5HTTLPR = serotonin transporter length polymorphic region; SCID-IP = Structured Clinical Interview for DSM IV Axis I disorders–Patient Edition; SCID-II = Structured Clinical Interview for DSM IV Axis II personality disorders; TCI-R = Temperament and Character Inventory Revised.

Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder

Plasma levels of melatonin and cortisol were measured over a 24-hour period in seven patients with primary obsessive-compulsive disorder (OCD) and seven matched healthy control subjects. In OCD patients, the 24-hour secretion of melatonin was reduced as compared with that in healthy control subjects, whereas its circadian rhythm was preserved. In addition, in OCD patients, the overall secretion of cortisol was higher than that in control subjects, but there was no change in the circadian pattern of cortisol secretion. No correlation was found between clinical parameters and hormone levels.

Aggressive Behavioral Characteristics and Endogenous Hormones in Women with Bulimia nervosa

Increased aggressiveness frequently occurs in patients with bulimia nervosa (BN), but its neurobiological correlates have been poorly investigated. In this study, we investigated possible relationships between such clinical measure and blood levels of endogenous hormones in patients with BN. Morning plasma levels of testosterone, 17β-estradiol, prolactin (PRL) and cortisol were measured in 33 bulimic women and 22 healthy female controls. The eating-related psychopathology, depression and aggressiveness were rated by specific psychometric scales. Bulimic patients showed decreased plasma levels of PRL and 17β-estradiol, and increased concentrations of cortisol and testosterone. Moreover, patients scored higher than healthy controls on rating scales assessing eating-related psychopathology, depressive symptoms and aggressiveness. A significant positive correlation was found between testosterone plasma levels and aggressiveness in patients but not in controls. These findings suggest that in BN, increased plasma levels of testosterone may play a role in the modulation of aggressiveness.

Temporal relationship between melatonin and cortisol responses to nighttime physical stress in humans

It has been shown that, in the rat, physical stress decreases pineal melatonin levels at night, whereas it increases melatonin production during the day. We have demonstrated that nighttime physical exercise is able to blunt the nocturnal surge of plasma melatonin in healthy subjects. Since this effect might be mediated by exercise-induced cortisol secretion from the adrenal gland, in the present investigation we studied the relationship between cortisol and melatonin responses to nighttime physical stress in six healthy men, aged 28-33 yr. The physical stress consisted of bicycling on a bicycle ergometer at 50% of personal maximum work capacity (MWC), followed by another 10 min of bicycling at 80% of MWC. According to our previous data, physical exercise performed between 2240 h and 2300 h significantly reduced the nocturnal surge of plasma melatonin and increased the levels of cortisol. The surge in plasma cortisol preceded the decrease in plasma melatonin concentration. These findings suggest a temporal relationship between plasma cortisol and melatonin responses to physical stress; the causal nature of this relationship remains to be elucidated.

Physical Stress in the Middle of the Dark Phase Does Not Affect Light-Depressed Plasma Melatonin Levels in Humans

The human pineal gland has been shown to be unresponsive to stress-induced sympathetic activation during the day. However, the effects of stress on human melatonin production have received little investigation at night, when the pinealocytes should be physiologically responsive to noradrenergic stimulation. For this purpose, plasma melatonin and cortisol levels were measured in 7 healthy men (aged 25-34 years), both in resting condition and before and after a physical exercise performed between 23.40 and 24.00 h, 30 min after exposure to bright light (2,500 lx). The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximum work capacity (MWC) for 10 min, followed by another 10 min of bicycling at 80% of the MWC. The results clearly showed that physical exercise does not affect light-depressed plasma melatonin levels, whereas it clearly increased plasma cortisol concentrations (p less than 0.002, two-way ANOVA with repeated measures), systolic blood pressure, pulse pressure and heart rate. These findings suggest that the human pineal gland is not responsive to systemic sympathetic activation induced by physical stress even in the middle of the dark phase.

Serotonin transporter polymorphism and potential response to SSRIs in bulimia nervosa

Sir—Selective serotonin reuptake inhibitors (SSRIs), alone or in combination with different psychotherapies and/or nutritional counselling, have been proved to reduce binge eating and vomiting frequencies in patients with bulimia nervosa (BN). However, percent reductions in bingeing and purging range from 18 to 87%.1 It has been suggested that the initial capacity, affinity or genotype of proteins involved in the regulation of SSRI action could account for differences in treatment outcome.2 The 5-HT transporter (5-HTT) represents the prime target of SSRIs, and a long (L) and a short (S) variant of the promoter region of the 5-HTT gene, with different transcriptional efficiencies, have been identified.3 The S allele of the 5-HTT gene-linked polymorphic region (5-HTTLPR) has been associated with poorer SSRI response in major depression.2, 4, 5, 6, 7

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.