Alessio Maria Monteleone

Abnormal diurnal patterns of salivary α-amylase and cortisol secretion in acute patients with anorexia nervosa.

Abstract Objectives. The evidence that the activity of the sympathetic nervous system (SNS) is decreased in acute anorexia nervosa (AN) is not consistent. Therefore, we aimed to assess the SNS basal activity in malnourished AN patients through the measurement of diurnal salivary levels of α-amylase, whose secretion is regulated by the SNS. As secondary aim, we measured also salivary cortisol. Methods. Eight symptomatic female patients with restrictive AN and eight age-matched healthy women underwent saliva sample collection at awakening and over the day. α-amylase and cortisol were assayed by ELISA method. Results. In both patients and controls, saliva α-amylase levels significantly decreased during 60 min after awakening and then progressively rose towards the afternoon/evening. AN patients exhibited significantly reduced levels of the salivary enzyme with a significant decrease in its overall diurnal secretion and a dysregulated secretory pattern. As compared to control women, AN patients exhibited significantly enhanced levels of salivary cortisol at awakening, an enhanced and advanced cortisol secretion after awakening but no significant change in the overall diurnal secretion of the salivary hormone. Conclusions. These results suggest that the activity of the SNS, evaluated through the assessment of the diurnal secretion of salivary α-amylase, is impaired in the acute phase of AN whereas the cortisol awakening response is enhanced.

Investigation of factors associated to crossover from anorexia nervosa restricting type (ANR) and anorexia nervosa binge-purging type (ANBP) to bulimia nervosa and comparison of bulimia nervosa patients with or without previous ANR or ANBP

OBJECTIVE To characterize factors associated to diagnostic crossover from anorexia nervosa restricting type (ANR) and anorexia nervosa binge-purging type (ANBP) to bulimia nervosa (BN) and to compare BN individuals with initial ANR or ANBP to subjects with stable BN. METHOD Two hundred thirty-eight patients with current and lifetime diagnosis of AN or BN underwent diagnostic, psychopathological, and historical examinations by means of ad hoc clinical interviews and rating scales. RESULTS One hundred twenty-three individuals had a stable BN. Seventy patients had a diagnosis of ANR and 45 of ANBP at the time of disease onset; 24 ANR patients and 23 ANBP subjects developed BN, whereas 46 ANR patients and 22 ANBP subjects did not crossover. Although the rate of diagnostic crossover was higher in the ANBP group than in the ANR one, the difference was not statistically significant. Longer illness duration, higher maximum past body mass index (BMI), higher novelty seeking, and lower self-directedness resulted significantly associated to crossover from ANR to BN, whereas higher maximum past BMI, higher desired body weight, higher novelty seeking, and lower harm avoidance were significantly associated to crossover from ANBP to BN. As compared to stable BN subjects, BN patients with initial ANR exhibited lower minimum past BMI, lower desired body weight, higher drive for thinness, ascetism, and social insecurity scores; BN patients with initial ANBP exhibited lower minimum past BMI and decreased enteroceptive awareness scores. CONCLUSIONS Different clinical and personality factors seem to be associated to crossover from ANR and ANBP to BN. Moreover, BN with initial ANR seems to differ clinically from stable BN. These findings may have therapeutic and prognostic implications.

The Acute Salivary Ghrelin Response to a Psychosocial Stress Is Enhanced in Symptomatic Patients with Bulimia Nervosa: A Pilot Study

Background: Stress is a precipitating factor for both binge eating and bulimia nervosa (BN); however, the biological mechanisms through which it may trigger binge eating are poorly understood. There is evidence that the adrenal hormone cortisol and the gastric peptide ghrelin might be involved in stress-induced food ingestion. We hypothesized that symptomatic patients with BN might disclose deranged responses of ghrelin and/or cortisol to stressors and that this could be related to their binge-eating behaviour. Methods: Here we investigated salivary cortisol and ghrelin responses to the Trier Social Stress Test (TSST) in 10 women with acute BN and 10 age-matched healthy females. Eating-related psychopathology and behaviours were assessed by self-report measures. Results: No significant differences emerged between bulimic patients and healthy controls in the pre-stress salivary levels of both cortisol and ghrelin. The BN patients displayed normal cortisol but enhanced ghrelin responses to TSST. No significant correlations emerged between stress-induced salivary hormone changes and self-report measures of binge eating. Conclusion: To our knowledge, this is the first study showing deranged salivary ghrelin reactivity to a psychosocial stressor in symptomatic patients with BN. The extent to which this could contribute to the binge-eating behaviour of BN subjects awaits clarification.

Flattened cortisol awakening response in chronic patients with schizophrenia onset after cannabis exposure

Cannabis may play a causal role in the onset of some schizophrenia cases; however, the biological vulnerability that predisposes some individuals to develop schizophrenia after exposure to cannabis is not known. According to the diathesis-stress pathogenetic model, it is likely that the endogenous stress response system, including the hypothalamus-pituitary-adrenal (HPA) axis, could be involved. Therefore, we investigated the saliva cortisol awakening response (CAR) of 16 patients with schizophrenia onset after the exposure to cannabis (Can+) as compared to 12 patients with schizophrenia onset without cannabis exposure (Can-) and to 15 healthy controls. The CAR was assessed by collecting saliva samples at awakening and after 15, 30 and 60 min. As compared to healthy controls, Can+ schizophrenia patients exhibited significantly enhanced baseline saliva cortisol levels and a flattened CAR. No significant abnormality in both baseline cortisol levels and CAR was detected in Can- schizophrenia patients. These findings demonstrate a dysregulation of the HPA axis in chronic schizophrenic patients whose illness started after cannabis exposure but not in those with an illness onset without cannabis exposure. Further studies need to clarify whether this HPA dysregulation is a part of the biological background underlying the increased risk to schizophrenia after exposure to cannabis.

Responses of peripheral endocannabinoids and endocannabinoid-related compounds to hedonic eating in obesity

PurposeHedonic eating occurs independently from homeostatic needs prompting the ingestion of pleasurable foods that are typically rich in fat, sugar and/or salt content. In normal weight healthy subjects, we found that before hedonic eating, plasma levels of 2-arachidonoylglycerol (2-AG) were higher than before nonhedonic eating, and although they progressively decreased after food ingestion in both eating conditions, they were significantly higher in hedonic eating. Plasma levels of anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), instead, progressively decreased in both eating conditions without significant differences. In this study, we investigated the responses of AEA, 2-AG, OEA and PEA to hedonic eating in obese individuals.MethodsPeripheral levels of AEA, 2-AG, OEA and PEA were measured in 14 obese patients after eating favourite (hedonic eating) and non-favourite (nonhedonic eating) foods in conditions of no homeostatic needs.ResultsPlasma levels of 2-AG increased after eating the favourite food, whereas they decreased after eating the non-favourite food, with the production of the endocannabinoid being significantly enhanced in hedonic eating. Plasma levels of AEA decreased progressively in nonhedonic eating, whereas they showed a decrease after the exposure to the favourite food followed by a return to baseline values after eating it. No significant differences emerged in plasma OEA and PEA responses to favourite and non-favourite food.ConclusionPresent findings compared with those obtained in our previously studied normal weight healthy subjects suggest deranged responses of endocannabinoids to food-related reward in obesity.

Central and Peripheral Peptides Regulating Eating Behaviour and Energy Homeostasis in Anorexia Nervosa and Bulimia Nervosa: A Literature Review

A large body of literature suggests the occurrence of a dysregulation in both central and peripheral modulators of appetite in patients with anorexia nervosa (AN) and bulimia nervosa (BN), but at the moment, the state or trait-dependent nature of those changes is far from being clear. It has been proposed, although not definitively proved, that peptide alterations, even when secondary to malnutrition and/or to aberrant eating behaviours, might contribute to the genesis and the maintenance of some symptomatic aspects of AN and BN, thus affecting the course and the prognosis of these disorders. This review focuses on the most significant literature studies that explored the physiology of those central and peripheral peptides, which have prominent effects on eating behaviour, body weight and energy homeostasis in patients with AN and BN. The relevance of peptide dysfunctions for the pathophysiology of eating disorders is critically discussed.

Childhood trauma and cortisol awakening response in symptomatic patients with anorexia nervosa and bulimia nervosa

OBJECTIVE Exposure to trauma during childhood is a risk factor for eating disorders (EDs) in adulthood. The biological mechanisms underlying such increased risk seem to involve the endogenous stress response system (i.e., the hypothalamic-pituitary-adrenal [HPA] axis), which undergoes trauma-induced functional changes that may persist later in life. In the present study, we examined the effects of childhood trauma experiences on HPA-axis activity, comparing saliva cortisol awakening response (CAR) in adult patients with anorexia nervosa (AN) or bulimia nervosa (BN) with CAR in adult healthy controls. METHOD Twenty-three patients with symptomatic AN, 21 patients with symptomatic BN, and 29 healthy women collected saliva samples at awakening and again after 15, 30, and 60 min. Participants also completed the Childhood Trauma Questionnaire and eating-related psychopathological rating scales. RESULTS According to the Childhood Trauma Questionnaire, 13 individuals with AN and 12 individuals with BN, but none of the healthy women, reported childhood maltreatment. Compared with the control group, the non-maltreated AN patient group exhibited an enhanced CAR, whereas the group of non-maltreated BN patients showed a normal CAR. Moreover, both AN and BN patient groups with childhood maltreatment exhibited statistically significant blunting of CAR compared with non-maltreated groups. DISCUSSION The present findings add to the evidence supporting the concept that there is a dysregulation of HPA-axis activity in symptomatic patients with EDs and suggest that childhood trauma exposure may contribute to such dysregulation.

Eating disorders: What age at onset?

Age at onset (AAO) of eating disorders has classically been described in adolescence. We analyzed data from 806 subjects with anorexia nervosa (AN) or bulimia nervosa (BN) and performed a normal distribution admixture analysis to determine their AAO. No significant differences were found concerning the AAO functions of AN and BN subjects. Both groups had a mean AAO of about 18 years. Most of the subjects with AN (75.3%) and BN (83.3%) belonged to the early onset group. The definition of AAO for ED may be crucial for planning treatment modalities, with specific consideration of their clinical history and course.

Gastroenteric hormone responses to hedonic eating in healthy humans.

Hedonic eating differentiates from homeostatic eating on two main aspects: the first one is that eating occurs when there is no need for calorie ingestion and the second one is that the food is consumed exclusively for its gustatory and rewarding properties. Gastroeneteric hormones such as ghrelin, colecystokinin-33 (CCK) and peptide YY3-36 (PYY3-36) are known to play a pivotal role in the homeostatic control of food intake. To the contrary, their role in hedonic eating has been never investigated. Here we report peripheral responses of CCK, PYY3-36 and ghrelin to the consumption of food for pleasure in well-nourished satiated healthy subjects. Plasma levels of CCK, PYY3-36 and ghrelin were measured in 7 satiated healthy subjects before and after ad libitum consumption of both a highly pleasurable food (hedonic eating) and an isoenergetic non-pleasurable food (non-hedonic eating). The consumption of food for pleasure was associated to a significantly increased production of the hunger hormone ghrelin and a significantly decreased secretion of the satiety hormone CCK. No significant changes in plasma PYY3-36 levels occurred in the two eating conditions. These preliminary data demonstrate that in hedonic eating the peripheral hunger signal represented by ghrelin secretion is enhanced while the satiety signal of CCK production is decreased. This could be responsible for the persistence of peripheral cues allowing a continued eating as well as for the activation of endogenous reward mechanisms, which can drive food consumption in spite of no energy need, only for reward.

Deranged endocannabinoid responses to hedonic eating in underweight and recently weight-restored patients with anorexia nervosa

BACKGROUND A dysregulation of reward mechanisms was suggested in the pathophysiology of anorexia nervosa (AN), but the role of the endogenous mediators of reward has been poorly investigated. Endocannabinoids, including anandamide and 2-arachidonoylglycerol, and the endocannabinoid-related compounds oleoylethanolamide and palmitoylethanolamide modulate food-related and unrelated reward. Hedonic eating, which is the consumption of food just for pleasure and not homeostatic need, is a suitable paradigm to explore food-related reward. OBJECTIVE We investigated responses of endocannabinoids and endocannabinoid-related compounds to hedonic eating in AN. DESIGN Peripheral concentrations of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, and palmitoylethanolamide were measured in 7 underweight and 7 weight-restored AN patients after eating favorite and nonfavorite foods in the condition of no homeostatic needs, and these measurements were compared with those of previously studied healthy control subjects. RESULTS 1) In healthy controls, plasma 2-arachidonoylglycerol concentrations decreased after both types of meals but were significantly higher in hedonic eating; in underweight AN patients, 2-arachidonoylglycerol concentrations did not show specific time patterns after eating either favorite or nonfavorite foods, whereas in weight-restored patients, 2-arachidonoylglycerol concentrations showed similar increases with both types of meals. 2) Anandamide plasma concentrations exhibited no differences in their response patterns to hedonic eating in the groups. 3) Compared with 2-arachidonoylglycerol, palmitoylethanolamide concentrations exhibited an opposite response pattern to hedonic eating in healthy controls; this pattern was partially preserved in underweight AN patients but not in weight-restored ones. 4) Like palmitoylethanolamide, oleoylethanolamide plasma concentrations tended to be higher in nonhedonic eating than in hedonic eating in healthy controls; moreover, no difference between healthy subjects and AN patients was observed for food-intake-induced changes in oleoylethanolamide concentrations. CONCLUSION These data confirm that endocannabinoids and endocannabinoid-related compounds are involved in food-related reward and suggest a dysregulation of their physiology in AN. This trial was registered at ISRCTN.org as ISRCTN64683774.