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Background: Childhood trauma is a non specific risk factor for adult eating disorders (ED), and the hypothalamic-pituitary-adrenal (HPA) axis seems to mediate such a risk. Here we explored the impact of different types of childhood trauma and of traumatic load on the cortisol awakening response (CAR) of women with anorexia nervosa (AN) or bulimia nervosa (BN). Methods: Saliva samples were collected at awakening and after 15, 30, 60 min to measure cortisol levels by 121 women (44 AN patients, 36 BN patients and 41 healthy women). Participants filled in the Childhood Trauma Questionnaire. Results: AN and BN patients with childhood maltreatment exhibited an attenuated CAR compared with non-maltreated ones. In the whole ED patient group, the CAR showed a progressive impairment with the increasing number of reported trauma types. Although significant negative correlations emerged between the type or the number of traumas and the CAR, only the number of traumas remained significantly associated with the CAR in a stepwise multiple regression analysis. Conclusions: Present findings confirm that childhood trauma is associated with an impaired CAR in adult AN and BN patients and demonstrate for the first time a negative dose-dependent effect of the traumatic load on HPA axis activity. [ABSTRACT FROM AUTHOR]

BackgroundSensitivity to punishment (SP) and sensitivity to reward (SR) are personality characteristics that may have relevance for the pathophysiology of eating disorders (EDs). Moreover, personality characteristics are known to modulate the activity of the hypothalamus–pituitary–adrenal (HPA) axis, which is the main component of the endogenous stress response system. As stress has been implicated in the aetiology and the maintenance of EDs, we aimed to study the HPA axis activity in relation to SP and SR, as conceptualized by Gray's reinforcement sensitivity theory (RST), in patients with anorexia nervosa (AN) or bulimia nervosa (BN).MethodTwenty-five women with AN, 23 women with BN and 19 healthy women volunteered for the study. HPA axis activity was assessed by measurement of the salivary cortisol awakening response (CAR). The subjects’ SP and SR were measured by the behavioural inhibition system (BIS)/behavioural approach system (BAS) scales.ResultsThe CAR was significantly enhanced in AN patients, but not in BN patients, compared to healthy women. The CAR correlated significantly with BAS measures, negatively in healthy controls and positively in binge-purging AN patients and BN women. SP, measured by the BIS scale, was higher in patients than in controls.ConclusionsThese findings confirm the occurrence of an enhanced activity of the HPA axis in symptomatic AN, but not in symptomatic BN, and show for the first time that the CAR is associated with SR, as conceptualized by the RST, negatively in healthy subjects but positively in binge-purging ED patients. [ABSTRACT FROM AUTHOR]

BackgroundThe stress response involves the activation of the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS). As a role for stress in determining of the onset and the natural course of eating disorders (EDs) has been proposed, the study of the psychobiology of the stress response in patients with anorexia nervosa (AN) and bulimia nervosa (BN) should be helpful in understanding the pathophysiology of these disorders. The two neurobiological components of the stress response can be easily explored in humans by the measurement of salivary cortisol and α-amylase response to a stressor. Therefore, we assessed salivary cortisol and α-amylase responses to the Trier Social Stress Test (TSST) in symptomatic patients with AN and BN compared to healthy controls.MethodSeven AN women, eight BN women and eight age-matched healthy females underwent the TSST between 1530 and 1700 h. Salivary cortisol and α-amylase levels were measured by an enzyme-linked immunosorbent assay (ELISA).ResultsCompared to healthy women, AN patients showed a normal cortisol response to the TSST, although this occurred at significantly increased hormone levels, and an almost complete absence of response of α-amylase. BN women, however, exhibited enhanced pre-stress levels of salivary α-amylase but a normal response of the enzyme and cortisol to the TSST.ConclusionsThese findings demonstrate, for the first time, the occurrence of an asymmetry between the HPA axis and SNS components of the stress response in the acute phase of AN but not in BN. The pathophysiological significance of this asymmetry remains to be determined. [ABSTRACT FROM AUTHOR]

BackgroundThe stress response involves the activation of the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS). As a role for stress in determining of the onset and the natural course of eating disorders (EDs) has been proposed, the study of the psychobiology of the stress response in patients with anorexia nervosa (AN) and bulimia nervosa (BN) should be helpful in understanding the pathophysiology of these disorders. The two neurobiological components of the stress response can be easily explored in humans by the measurement of salivary cortisol and α-amylase response to a stressor. Therefore, we assessed salivary cortisol and α-amylase responses to the Trier Social Stress Test (TSST) in symptomatic patients with AN and BN compared to healthy controls.MethodSeven AN women, eight BN women and eight age-matched healthy females underwent the TSST between 1530 and 1700 h. Salivary cortisol and α-amylase levels were measured by an enzyme-linked immunosorbent assay (ELISA).ResultsCompared to healthy women, AN patients showed a normal cortisol response to the TSST, although this occurred at significantly increased hormone levels, and an almost complete absence of response of α-amylase. BN women, however, exhibited enhanced pre-stress levels of salivary α-amylase but a normal response of the enzyme and cortisol to the TSST.ConclusionsThese findings demonstrate, for the first time, the occurrence of an asymmetry between the HPA axis and SNS components of the stress response in the acute phase of AN but not in BN. The pathophysiological significance of this asymmetry remains to be determined. [ABSTRACT FROM PUBLISHER]

Endocannabinoids modulate eating behavior; hence, endocannabinoid genes may contribute to the biological vulnerability to eating disorders. The rs1049353 (1359 G/A) single nucleotide polymorphism (SNP) of the gene coding the endocannabinoid CB1 receptor ( CNR1) and the rs324420 (cDNA 385C to A) SNP of the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, have been suggested to have functional effects on mature proteins. Therefore, we explored the possibility that those SNPs were associated to anorexia nervosa and/or bulimia nervosa. The distributions of the CNR1 1359 G/A SNP and of the FAAH cDNA 385C to A SNP were investigated in 134 patients with anorexia nervosa, 180 patients with bulimia nervosa and 148 normal weight healthy controls. Additive effects of the two SNPs in the genetic susceptibility to anorexia nervosa and bulimia nervosa were also tested. As compared to healthy controls, anorexic and bulimic patients showed significantly higher frequencies of the AG genotype and the A allele of the CNR1 1359 G/A SNP. Similarly, the AC genotype and the A allele of the FAAH cDNA 385C to A SNP were significantly more frequent in anorexic and bulimic individuals. A synergistic effect of the two SNPs was evident in anorexia nervosa but not in bulimia nervosa. Present findings show for the first time that the CNR1 1359 G/A SNP and the FAAH cDNA 385C to A SNP are significantly associated to anorexia nervosa and bulimia nervosa, and demonstrate a synergistic effect of the two SNPs in anorexia nervosa. [ABSTRACT FROM AUTHOR]

Objectives: Brain-derived neurotrophic factor (BDNF) has been proposed as a candidate molecule in the pathophysiology of major depressive disorder (MDD) and bipolar disorders (BD). Reduced levels of peripheral BDNF have been found in drug-free MDD patients, in drug-treated depressed or manic patients with BD type I (BD-I), but not in drug-treated euthymic BD-I individuals. No study has been done in patients with BD type II (BD-II). Moreover, the influence of Axis I psychiatric comorbidity on circulating BDNF in affective patients has never been evaluated. Therefore, in the present study, we aimed: (i) to confirm previous findings on peripheral BDNF in MDD and BD-I patients; (ii) to assess whether changes in circulating BDNF occur also in patients with BD-II; and (iii) to exclude the possibility that comorbid psychiatric disorders exerted an effect on BDNF levels in affective patients. Methods: We measured serum BDNF concentrations by an enzyme-linked immunosorbent assay method in 85 subjects, including 24 euthymic patients with unipolar depression (UD), 17 euthymic patients with BD-I, 11 euthymic patients with BD-II, 11 UD patients with a current major depressive episode and 22 drug-free healthy controls. At the time of the study, 15 patients were drug-treated; the remaining ones were drug-free for at least four weeks. Results: Compared to healthy controls, serum BDNF concentrations were significantly reduced in all the patient groups ( F4,80 = 3.840, p = 0.006) with no significant difference among them. Drug treatments and comorbid psychiatric disorders had no effect on lowered circulating BDNF levels in affective patients. Conclusions: Present results confirm previous independent findings of reduced circulating BDNF in patients with MDD and report, for the first time, decreased serum BDNF levels in euthymic patients with UD, BD-I and BD-II, independently from drug treatment status and concomitant Axis I psychiatric disorders. [ABSTRACT FROM AUTHOR]

Purpose The aim of the study was to measure circulating BDNF levels, a neurotrophin recently identified in the ovary, in parallel with estradiol, to verify if assessing this factor could add any predictive value to the outcome of in vitro fertilization. Methods Blood sampling for BDNF and estradiol was performed in 23 subjects undergoing IVF on day 1 (D1), day 8 (D8), day of HCG administration (DHCG) and day of oocyte retrieval.(DOR). Results There was a positive correlation between BDNF and estradiol throughout the stimulation cycle in all subjects. In both pregnant and nonpregnant patients, the values of BDNF grew significantly only between D8 and DHCG and remained constant until DOR. Between-group comparisons showed no statistically significant differences in both BDNF and estradiol values throughout the IVF cycle. Conclusion Although BDNF plasma concentrations are not seemingly predictive of IVF outcome, this neurotrophin is highly correlated to estradiol levels and seems to be an important factor especially in the periovulatory period. [ABSTRACT FROM AUTHOR]

Summary: Background: Olanzapine (OLA) administration has been reported to induce weight gain in experimental animals and humans, through not yet fully defined mechanisms of action. Aim of this study was to determine whether in patients with Anorexia Nervosa (AN) OLA induces weight gain through the modulation of the hunger-satiety regulatory peptides leptin and ghrelin. Methods: Twenty anorexic probands received a 3 months course of cognitive-behavioral psychotherapy and programmed nutritional rehabilitation, combined with OLA PO (2.5mg for 1 month and 5mg for 2 months) in ten patients and with placebo PO (PL) in the other 10. Weight, measured as body mass index (BMI), leptin and ghrelin plasma values were monitored before starting the therapy and then monthly for 3 months. Plasma leptin was measured by ELISA, and plasma ghrelin by radioimmunoassay. Results: BMI increased significantly but not differently in both treatment groups. Leptin and ghrelin secretion did not change during the course of the treatments. No correlations were observed between BMI values and leptin and ghrelin levels. Conclusions: Our data suggest that the weight gain observed in our OLA-treated patients was not linked to drug administration. Moreover, leptin and ghrelin secretions were not responsible for BMI changes. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Backgrounds We designed a two-step prospective study aiming to detect cases with full and atypical eating disorders (EDs) in a population of female high-school students (first step) and to assess their natural outcome after a 4-year time period (second step). Methods In the first step, we screened female students in their first year of high school by means of the EDI-2 and GHQ-28 questionnaires. Those students identified as being at risk for an ED underwent a psychiatric interview. In the second step, 4 years later, we tested schoolgirls in their last year of high school by adopting the same procedure as the first step. Results 140 subjects participated in both steps. In the first step, we identified one subject with full-blown bulimia nervosa (BN), one with partial-syndrome BN, two with subclinical BN and eight with subclinical anorexia nervosa (AN). At the reassessment 4 years later, none of the girls had received any form of help. The full-blown BN case, the partial-syndrome BN case and one of the subclinical AN cases persisted unchanged; one of the subclinical BN cases shifted to subclinical AN; the remaining subclinical cases remitted spontaneously. Moreover, we identified 12 new cases of EDs. Conclusions Present findings provide the first evidence that subclinical AN and subclinical BN represent unstable states that can spontaneously remit over time. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association. [ABSTRACT FROM AUTHOR]

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-1β (Il-1β) and tumor necrosis factor-α (TNF-α) 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-1β levels were not significantly different in MDD from controls and significantly higher than normal in DYS subjects. TNF-α 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. [Copyright &y& Elsevier]

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.Molecular Psychiatry (2004) 9, 76-80. doi:10.1038/sj.mp.4001374 [ABSTRACT FROM AUTHOR]

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[sub αs], G[sub αi], G[sub αq/11] and G[sub β] 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[sub αi] and G[sub β] proteins, while bulimic patients had significantly increased levels of G[sub αs], G[sub αi] and G[sub β] 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. [ABSTRACT FROM AUTHOR]

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 bingeeating 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 Oh-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 nonbinge-eating obese subjects. These results show, for the first time, that opposite modifications occur in circulating levels of leptin and Oh-Re across the eating-disorder spectrum. The relevance of these findings to the pathophysiology and treatment of eating disorders remains to be elucidated. [ABSTRACT FROM AUTHOR]

Abstract The aim of this study was to examine whether anorexia nervosa and bulimia nervosa are accompanied by lower serum activity of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5), a membrane-bound serine protease that catalyses the cleavage of dipeptides from the amino-terminus of oligo- and polypeptides. Substrates of DPP IV are, amongst others, neuroactive eptides, such as substance P, growth hormone releasing hormone, neuropeptide Y, and peptide YY. DPP IV activity was measured in the serum of 21 women with anorexia nervosa, 21 women with bulimia nervosa and 18 normal women. Serum DPP IV activity was significantly lower in patients with anorexia nervosa and bulimia nervosa than in the normal controls. In the total study group, there were significant and inverse relationships between serum DPP IV activity and the total scores on the Bulimic Investigatory Test, Edinburgh, the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale. In the total study group no significant correlations between DPP IV and age, body weight or body mass index could be found. It is concluded that lowered serum DPP IV activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesised that a combined dysregulation of DPP IV and neuroactive peptides, which are substrates of DPP IV, e.g. neuropeptide Y and peptide YY, could be an integral component of eating disorders. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about serotonin transporter polymorphism and potential response to selective serotonin reuptake inhibitors in bulimia nervosa.

IVF embryos have historically been evaluated by morphological characteristics. The time-lapse system (TLS) has become a promising tool, providing an uninterrupted evaluation of morphological and dynamic parameters of embryo development. Furthermore, TLS sheds light on unknown phenomena such as direct cleavage and incomplete morula compaction. We retrospectively analyzed the morphology (Gardner Score) and morphokinetics (KIDScore) of 835 blastocysts grown in a TLS incubator (Embryoscope+), which were biopsied for preimplantation genetic testing for aneuploidy (PGT-A). Only the embryos that reached the blastocyst stage were included in this study and time-lapse videos were retrospectively reanalysed. According to the pattern of initial cleavages and morula compaction, the embryos were classified as: normal (NC) or abnormal (AC) cleavage, and fully (FCM) or partially compacted (PCM) morulae. No difference was found in early cleavage types or morula compaction patterns between female age groups (< 38, 38–40 and > 40 yo). Most of NC embryos resulted in FCM (≅ 60%), while no embryos with AC resulted in FCM. Aneuploidy rate of AC-PCM group did not differ from that of NC-FCM group in women < 38 yo, but aneuploidy was significantly higher in AC-PCM compared to NC-FCM of women > 40 yo. However, the quality of embryos was lower in AC-PCM blastocysts in women of all age ranges. Morphological and morphokinetic scores declined with increasing age, in the NC-PCM and AC-PCM groups, compared to the NC-FCM. Similar aneuploidy rates among NC-FCM and AC-PCM groups support the hypothesis that PCM in anomalous-cleaved embryos can represent a potential correction mechanism, even though lower morphological/morphokinetic scores are seen on AC-PCM. Therefore, both morphological and morphokinetic assessment should consider these embryonic development phenomena. [ABSTRACT FROM AUTHOR]

IVF embryos have historically been evaluated by morphological characteristics. The time-lapse system (TLS) has become a promising tool, providing an uninterrupted evaluation of morphological and dynamic parameters of embryo development. Furthermore, TLS sheds light on unknown phenomena such as direct cleavage and incomplete morula compaction. We retrospectively analyzed the morphology (Gardner Score) and morphokinetics (KIDScore) of 835 blastocysts grown in a TLS incubator (Embryoscope+), which were biopsied for preimplantation genetic testing for aneuploidy (PGT-A). Only the embryos that reached the blastocyst stage were included in this study and time-lapse videos were retrospectively reanalysed. According to the pattern of initial cleavages and morula compaction, the embryos were classified as: normal (NC) or abnormal (AC) cleavage, and fully (FCM) or partially compacted (PCM) morulae. No difference was found in early cleavage types or morula compaction patterns between female age groups (< 38, 38–40 and > 40 yo). Most of NC embryos resulted in FCM (≅ 60%), while no embryos with AC resulted in FCM. Aneuploidy rate of AC-PCM group did not differ from that of NC-FCM group in women < 38 yo, but aneuploidy was significantly higher in AC-PCM compared to NC-FCM of women > 40 yo. However, the quality of embryos was lower in AC-PCM blastocysts in women of all age ranges. Morphological and morphokinetic scores declined with increasing age, in the NC-PCM and AC-PCM groups, compared to the NC-FCM. Similar aneuploidy rates among NC-FCM and AC-PCM groups support the hypothesis that PCM in anomalous-cleaved embryos can represent a potential correction mechanism, even though lower morphological/morphokinetic scores are seen on AC-PCM. Therefore, both morphological and morphokinetic assessment should consider these embryonic development phenomena. [ABSTRACT FROM AUTHOR]

Introduction: Eating disorders (EDs) exist on a continuum ranging from innocuous but persisting dieting, through subthreshold states of uncertain significance, to full-blown cases of anorexia nervosa (AN) and bulimia nervosa (BN). Subthreshold EDs resemble AN or BN, but do not meet all their diagnostic criteria. The terms “partial syndromes” and “atypical EDs” are also used to identify these conditions.Objectives. To verify whether atypical syndromes are less severe forms of EDs or represent starting phases of EDs, we designed a two-step prospective study assessing the natural outcome of those syndromes over a 4-year time period. Methods: In the first step, we screened 495 female students attending the first year of their high school by means of ad hoc rating questionnaires. Those students identified to being at risk for an ED underwent a psychiatric diagnostic interview. In the second step, 4 years later, we reassessed 140 of those schoolgirls who had participated in the first step. Results: In the first step, we identified 1 subject with full-blown BN, 1 with partial-syndrome BN, 2 with subclinical BN and 8 with subclinical AN. At the reassessment 4 years later, none of the girls had received any form of help. The full-blown BN case, the partial-syndrome BN case and 1 of the subclinical AN cases persisted unchanged; 1 of the subclinical BN cases shifted to subclinical AN; the remaining subclinical cases remitted spontaneously. Conclusions: Present findings provide the evidence that subclinical AN and subclinical BN represent unstable states that can spontaneously remit over time. [Copyright &y& Elsevier]

Purpose: Hedonic 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. Methods: Peripheral 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. Results: Plasma 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. Conclusion: Present findings compared with those obtained in our previously studied normal weight healthy subjects suggest deranged responses of endocannabinoids to food-related reward in obesity. [ABSTRACT FROM AUTHOR]

Introduction: Bipolar Disorder (BD) is a severely debilitating psychiatric disorder with high rates of morbidity and mortality, and patients with BD have a 10-year reduction in their life expectancy. Bipolar disorder (BD) is frequently associated with type 2 diabetes mellitus (T2DM). BD patients with comorbid T2DM have been shown to have three times higher odds of a chronic course and rapid cycling and are more likely to present worse outcomes to treatment with lithium and/or other mood stabilisers when compared to BD patients without IGM (impaired glucose metabolism). Objectives: The functioning of the hypothalamic-pituitary-adrenal (HPA) axis has been never investigated in BD with respect to the glucose metabolic status. Therefore, we assessed the cortisol awakening response (CAR) in bipolar patients with or without comorbid T2DM. Methods: Twenty euglycemic bipolar patients [12 males and eight females; mean age (±SD): 47.4 ± 14.4 years; mean (±SD) duration of illness: 18.3 ± 12.1 years], 16 BD patients with T2DM [11 males and five females; mean age (±SD): 63.6 ± 12.8 years; mean (±SD) duration of bipolar illness: 17.1 ± 10.8 years; mean (±SD) duration of T2DM: 5.2 ± 5.3 years], 18 healthy subjects [seven males and 11 females; mean age (±SD): 45.0 ± 12.1 years] and 12 non-psychiatric subjects with T2DM [eight males and four females; mean age (±SD): 56.7 ± 11.2 years; mean (±SD) duration of T2DM: 5.2 ± 3.5 years] were recruited. Saliva cortisol was measured at awakening and after 15, 30, and 60 min. Results: With respect to both healthy controls and controls with T2DM, euglycemic and diabetic BD patients exhibited a CAR occurring at significantly lower levels. No significant difference emerged in the CAR between the two groups of bipolar patients. Controls with T2DM had an overall post-awakening cortisol production significantly higher than healthy controls. Conclusions: Our results show that the CAR of patients with BD is reduced in terms of overall cortisol production but normal in terms of cortisolo reactivity independently from the occurrence of comorbid T2DM. The dampened CAR points to a tuning down of the functioning of the HPA axis in both euglycemic and diabetic BD patients, which may be a factor of vulnerability, since a preserved HPA axis functioning is essential to deal with stressors, which may precipitate affective episodes Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Existing multi-layer devices using lead-based piezoelectric ceramics utilize an internal electrode that does not bond the ceramic layers. Improvements in device performance and processing could be gained if the electrode also acted as a bond between the ceramic layers. In the current work, the feasibility of brazing lead zirconate titanate (PZT) in ambient conditions utilizing silver-based alloys containing low melting temperature metal oxides was investigated. Wettability, joint fracture strength, and microstructural analyses were conducted for various PZT/silver–metal oxide systems. The metal oxide additions included copper (II) oxide, vanadium pentoxide, lead (II) oxide, and eutectic lead oxide-titanium (IV) oxide. The silver–copper oxide (Ag–CuO) system demonstrated the most potential; exhibiting an apparent contact angle of approximately 64° and an average braze joint fracture strength that was approximately 62% of the monolithic PZT strength. In addition, no significant reaction product formation was observed at the silver/PZT interface. However, a preliminary investigation of multi-layer devices electroded with Ag–CuO alloys indicated a decrease in the resistivity of the brazed PZT by several orders of magnitude. [ABSTRACT FROM AUTHOR]

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 20fertile healthy women in the follicular and the luteal phases. Adrenocorticotropic hormone (ACTH) tests after dexamethasone suppression were per-formed in 10 patients of each group during the follicular and the luteal phases. In the PMS group, significantly lower allopregnanolone 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 level 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 literal secretion of allo-pregnanolone, 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. [ABSTRACT FROM AUTHOR]

Introduction: Aggressive behaviors have been reported to be more frequent in people with eating disorders (ED), especially bulimia nervosa (BN). Network Analysis (NA) is particularly useful or examining the interactions among symptoms of comorbid conditions through the identification of "bridge symptoms," defined as those symptoms playing a key role in the connection between two syndromic clusters. Objectives: The aim of the present study was to investigate the association of ED core symptoms and ED-related psychopathology with aggressiveness in a clinical sample of women with BN through NA. Methods: A NA was conducted, including ED symptoms and aggressiveness measures. The bridge function was implied to identify symptoms bridging ED symptoms and aggressiveness. Results: The most connected nodes among communities were asceticism and impulsivity from ED-related psychopathology, drive for thinness from ED- core psychopathology and guilt and suspicion from aggressiveness domain. In particular, drive for thinness connected ED-core community to verbal hostility, while impulsivity connected ED-related symptoms to guilt and suspicion of aggressiveness community. Conclusions: In conclusion the present study showed that in people with BN guilt is the specific negative emotion of the hostile dimensions that may be bidirectionally associated with ED symptoms. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Childhood maltreatment (CM) is associated with distinct clinical and biologi- cal characteristics in people with eating disorders (EDs). The measurement of local gyrification index (lGI) may help to better characterize the impact of CM on cortical structure. Objectives: The objective of this study was to investigate the association of CM with lGI in women with EDs. Methods: Twenty-six women with anorexia nervosa (AN) and 24 with bulimia nervosa (BN) underwent a 3T MRI scan. All partici- pants filled in the Childhood Trauma Questionnaire. All neuroimaging data were processed by FreeSurfer. LGI maps underwent a general linear model to evaluate differences between groups with or without CM. People with AN and BN were merged together. Results: Based on the Childhood Trauma Questionnaire cut- off scores, 24 participants were identified as maltreated and 26 as non- maltreated. Maltreated people with EDs showed a significantly lower lGI in the left middle temporal gyrus compared with non-maltreated people, whereas no differences emerged in the right hemisphere between groups. Conclusions: The present study showed that in people with EDs, CM is associated with reduced cortical folding in the left middle temporal gyrus, an area that could be involved in ED psychopathology. This finding corroborates the hypothesis of a 'maltreated ecophenotype', which argues that CM may allow to biologically, other than clinically, distinguish individuals with the same psychiatric disorder. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Early life experiences may have an impact on hypothalamic–pituitary–adrenal (HPA) axis functioning in eating disorders (EDs). Parental bonding is defined as the parental contribution of care and control to parent–child relationships. We evaluated whether perceived care and protection of parental bonding in childhood and adolescence were associated with HPA axis functioning in adult patients with EDs. The activity of the HPA axis was assessed by measuring the salivary cortisol awakening response (CAR). Objectives: We evaluated whether parental care and control in childhood and adolescence were associated with HPA axis functioning in adults with EDs. On the basis of literature data on healthy participants, we hypothesized that people with high levels of parental care would show a reduced CAR compared to people with low levels of parental care. Methods: We admitted patients according to the following inclusion criteria: (a) female sex, (b) age > 18 years, (c) current diagnosis of AN or BN according to DSM-5 criteria, (d) absence of severe physical disorders, (e) no history of endocrine disorders, psychoactive substance use, schizophrenia or other psychoses, bipolar disorders or head trauma. Participants completed the Italian version of the Parental Bonding Instrument (PBI). To measure the CAR, participants were instructed to collect saliva samples at awakening and 15, 30, and 60 min after awakening. Results: 64 women with EDs participated in the study: 37 with AN and 27 with BN. 28 participants reported low levels of both maternal and paternal care while 12 participants reported high levels of care from both parents; 31 participants reported high levels of both maternal and paternal control, while 12 participants reported low levels of control from both parents. When maternal care was entered as between factor in the analysis, the repeated measures 3-way ANOVA showed a significant time effect (F3, 180 = 2.81, p < 0.05) and a significant maternal care X time interaction (F3, 180 = 2.99, p < 0.05), while, when paternal care was entered as between factor, the repeated measures 3-way ANOVA did not show significant effects for time and no significant paternal care X time interaction. Conclusions: Our results show an association of perceived maternal care with the time pattern of CAR in female patients with ED, while perceived parental control was not associated with any CAR feature in EDs. Maternal control, paternal care and paternal control were not associated with any difference in the CAR. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Purpose: Worldwide publications follow the gold standard method—the polymerase chain reaction (PCR)—for detecting Y-chromosome microdeletions; however, markers are frequently variable between the studies. Can we detect the deletions by another molecular method with more genomic coverage? The Y chromosome harbors several different genes responsible for testicular development and spermatogenesis, and its repetitive conformation predisposes it to complex rearrangements that have clinical impact. Our aim was to evaluate a molecular diagnostic method, the Multiplex Ligand Probe-dependent Amplification (MLPA), which is also a valuable ancillary method for the identification of deletions, duplications, and rearrangements in a single and faster reaction, leading to a better comprehension of patients' phenotypes, and should be considered a useful tool for detection of Y chromosome deletions. Methods: This is a study of diagnostic accuracy (transversal prospective study) conducted to investigate Y-chromosome deletions in 84 individuals through PCR and MLPA methods. Forty-three infertile men (azoospermic and oligozoospermic) and 41 controls (40 fertile men and 1 normal karyotyped woman) were analyzed by PCR and MLPA techniques. Results: We diagnosed seven (7) deletions (16.2%) by PCR and 9 with MLPA (21%). In addition, we found five (5) duplications and a suggestive mosaic. Conclusion: Our results demonstrate that MLPA technique is valuable in the investigation of microdeletions and microduplications. Besides deletions, duplications can cause instability of chromosome genes, possibly leading to infertility. Both studied techniques provide an advantageous diagnostic strategy, thus enabling a better genetic counseling. [ABSTRACT FROM AUTHOR]

Background: A general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia.Methods: We used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia.Results: We found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC).Conclusions: Overall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment. Method: Premorbid adjustment (PA) in patients with schizophrenia was compared to early adjustment in unaffected first‐degree relatives and healthy controls. Its associations with psychopathology, cognition, and real‐life functioning were investigated. The associations of PA with primary negative symptoms and their two factors were explored. Results: We found an impairment of academic and social PA in patients (P ≤ 0.000001) and an impairment of academic aspects of early adjustment in relatives (P ≤ 0.01). Patients with poor PA showed greater severity of negative symptoms (limited to avolition after excluding the effect of depression/parkinsonism), working memory, social cognition, and real‐life functioning (P ≤ 0.01 to ≤0.000001). Worse academic and social PA were associated with greater severity of psychopathology, cognitive impairment, and real‐life functioning impairment (P ≤ 0.000001). Regression analyses showed that worse PA in the academic domain was mainly associated to the impairment of working memory, whereas worse PA in the social domain to avolition (P ≤ 0.000001). Conclusion: Our findings suggest that poor early adjustment may represent a marker of vulnerability to schizophrenia and highlight the need for preventive/early interventions based on psychosocial and/or cognitive programs. [ABSTRACT FROM AUTHOR]

It is a known fact that abnormal seminal liquid specimens contain abnormal amounts of oxygen free radicals and reactive oxygen species (ROS), and that the use of antioxidant molecules bothin vivoandin vitroleads to improvement of semen quality in terms of motility, reduction in DNA damage, with obvious consequences on the fertilization potential. Myo-inositol has been observed to have anti-oxidant properties and be present in much greater concentrations specifically in seminal liquid than in the blood. Moreover, there seems to be a direct relationship between myo-inositol and mitochondrial membrane potential (MMP) and sperm motility. Studies performedin vivohave demonstrated that a dietary supplementation with myo-inositol in men undergoing assisted reproduction techniques may improve sperm quality and motility in oligoasthenospermia (OAT) patients. In the following study we utilized myo-inositolin vitroto verify its effect on semen quality in both normal and OAT patients undergoingin vitrofertilization (IVF) with respect to standard sperm medium.In vitroincubation of seminal liquid carried out using myo-inositol (Andrositol-Lab, Lo.Li. Pharma-Roma, Italy) at a concentration of 15 μl/ml improved progressive motility in both normospermia and OAT subjects. In our opinion, myo-inositol may prove to be a useful strategy to improve sperm preparation for clinical use in IVF. [ABSTRACT FROM PUBLISHER]

Obese patients have decreased fasting and postprandial levels of peptide YY (PYY), an anorexigenic peptide produced by the L cells of the gastrointestinal mucosa. Fatty nutrients are the most powerful stimulus for PYY release. Cholestyramine, an anion exchanger which adsorbs bile salts, reduces digestion of lipids. The aim of the present study was to investigate the effects of cholestyramine or placebo on PYY secretion in obese women administered a high-fat meal [n = 8; age: 30.9 ± 2.7 years; BMI: 47.3 ± 3.3 kg/m2]. Postprandial PYY levels in obese women given placebo significantly increased in plasma at 30, 60, 90, and 120 min after meal ingestion. Cholestyramine administration significantly reduced postprandial PYY response at 15, 30, and 60 min. Percent fat mass (FM %) was negatively correlated with the percent increment of plasma PYY concentrations induced by meal administration at 30 min; conversely, there was a positive correlation between FM % and the percent decrement of plasma PYY concentrations induced by cholestyramine at the same time interval. These correlations failed to reach statistical significance when related to BMI. This study implies that in the obese state the altered PYY response to food consumption is a consequence of a dysfunction of L cells, which become less sensitive to the positive feedback effect of lipids. [ABSTRACT FROM AUTHOR]

BackgroundStudies investigating neurocognitive impairment in subjects with eating disorders (EDs) have reported heterogeneous patterns of impairment and, in some instances, no dysfunction. The present study aimed to define the pattern of neurocognitive impairment in a large sample of bulimia nervosa (BN) patients and to demonstrate that neuroendocrine, personality and clinical characteristics influence neurocognitive performance in BN.MethodAttention/immediate memory, set shifting, perseveration, conditional and implicit learning were evaluated in 83 untreated female patients with BN and 77 healthy controls (HC). Cortisol and 17β-estradiol plasma levels were assessed. Cloninger's Temperament and Character Inventory – Revised (TCI-R), the Bulimic Investigation Test Edinburgh (BITE) and the Montgomery–Asberg Depression Rating Scale (MADRS) were administered.ResultsNo impairment of cognitive performance was found in subjects with BN compared with HC. Cortisol and ‘Self-directedness’ were associated with better performance on conditional learning whereas 17β-estradiol had a negative influence on this domain; ‘Reward dependence’ was associated with worse performance on implicit learning; and depressive symptomatology influenced performance on the Wisconsin Card Sorting Test (WCST) negatively.ConclusionsNo cognitive impairment was found in untreated patients with BN. Neuroendocrine, personality and clinical variables do influence neurocognitive functioning and might explain discrepancies in literature findings. [ABSTRACT FROM PUBLISHER]

The endocannabinoid, arachidonoylethanolamide (AEA), and the peroxisome proliferator-activated receptor (PPAR)-alpha ligand, oleylethanolamide (OEA) produce opposite effects on lipogenesis. The regulation of OEA and its anti-inflammatory congener, palmitoylethanolamide (PEA), in adipocytes and pancreatic beta-cells has not been investigated. We report here the results of studies on acylethanolamide regulation in these cells during obesity and hyperglycaemia, and provide an overview of acylethanolamide role in metabolic control. We analysed by liquid chromatography-mass spectrometry OEA and PEA levels in: 1) mouse 3T3F442A adipocytes during insulin-induced differentiation, 2) rat insulinoma RIN m5F beta-cells kept in 'low' or 'high' glucose, 3) adipose tissue and pancreas of mice with high fat diet-induced obesity (DIO), and 4) in visceral fat or blood of obese or type 2 diabetes (T2D) patients. In adipocytes, OEA levels remain unchanged during differentiation, whereas those of PEA decrease significantly, and are under the negative control of both leptin and PPAR-gamma. PEA is significantly downregulated in subcutaneous adipose tissue of DIO mice. In RIN m5F insulinoma beta-cells, OEA and PEA levels are inhibited by 'very high' glucose, this effect being enhanced by insulin, whereas in cells kept for 24 h in 'high' glucose, they are stimulated by both glucose and insulin. Elevated OEA and PEA levels are found in the blood of T2D patients. Reduced PEA levels in hypertrophic adipocytes might play a role in obesity-related pro-inflammatory states. In beta-cells and human blood, OEA and PEA are down- or up-regulated under conditions of transient or chronic hyperglycaemia, respectively. [ABSTRACT FROM AUTHOR]

Abnormalities of resting state EEG, both in time and frequency domains, were consistently reported in subjects with schizophrenia (SCZ) [2]. B Methods: b Our sample, recruited at five research sites as part of the add-on EEG study of the Italian Network for Research on Psychoses, consisted of 113 SCZ and 57 HC. Illness-related and functioning-related variables were measured at baseline in the whole group of SCZ, and after four-year follow-up in 61 SCZ. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite of conventional morphological evaluation is the classical method for embryo selection it clearly has limitations. Recently, time-lapse monitoring allows the embryo quality classification based on morphokinetics. Moreover, Preimplantation Genetic Test for Aneuploidy (PGT-A) is applied to investigate the genetic status of the embryos and the selection of euploid embryos for transfer is supposed to lead to improved clinical outcomes. The association of morphokinetics and PGT-A opened new opportunities to refine blastocyst selection. However, knowledge of the impact of chromosome alterations on embryo morphokinetics need to be increased. The aim of this study was to correlate embryo score from time-lapse imaging with chromosome status of the embryos evaluated by PGT-A. This is a preliminary retrospective cohort study of prospectively collected data for 81 ICSI cycles performed at a private assisted reproduction center in Brazil, between April and November 2018. A total of 260 embryos developed into blastocysts suitable for biopsy and were analyzed in this study. Embryos were cultured in the Embryoscope® time-lapse imaging chamber (Vitrolife®) and the image acquisition system was set to capture images from each embryo every 15 minutes during the entire culture interval. Embryos were scored from zero to 10 based on the timings of cell divisions with the start of ICSI until the blastocyst formation and expansion on day 5 or 6 of development. PGT-A was elective, but strongly encouraged for patient's ≥37 years old, implantation failure, recurrent miscarriage or severe male factor cases. Embryos were biopsied at a blastocyst stage and PGT-A was carried out at a global reference laboratory (Igenomix Brasil) through NGS. The women age varied from 25 to 42 years (38.5±2.9) and 1 to 10 blastocysts were biopsied per patient (3.2±2.0). Of the 260 biopsied blastocyst, 38.7% were euploid. The embryos scores were slightly lower in aneuploid (5.9±2.1) than euploid (6.4±2.1) blastocysts with a marginally significant statistical difference (p=0.067). The number of altered chromosomes were annotated and inversely correlated to embryo score (Pearson correlation: r=-0.210; p=0.001). Then we classified the number of altered chromosomes as none (euploid), 1-2, 3-6 and more than 6 (chaotic). We only observed a significant difference between the time-lapse embryo score of chaotic (3.9±1.3) and euploid (6.4±2.1; p=0.026) blastocysts. The 1-2 (6.1±2.0) or 3-6 (5.4±2.3) alterations showed similar time-lapse embryo score to euploid embryos (p=1.000 and p=0.161, respectively). The multivariate linear regression model have confirmed the higher number of altered chromosomes lower the time-lapse embryo score (Coef=-0.149; p=0.026) adjusted for confounders as women age and time of culture. The findings of our study suggest the number of altered chromosomes affect the embryo morphokinetics, leading to a reducing time-lapse embryo score. Although there seems to be a relationship between the ploidy status and complexity of chromosome alterations with the embryo morphokinetics, time-lapse embryo score is not enough to predict chromosome alterations, and therefore, replace PGT-A. These are preliminary outcomes and further studies are being conducted to investigate the association of chromosome alterations with embryo morphokinetics and relate them with clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Despite innovative treatments, the impairment in real-life functioning in subjects with schizophrenia (SCZ) remains an unmet need in the care of these patients. Recently, real-life functioning in SCZ was associated with abnormalities in different electrophysiological indices. It is still not clear whether this relationship is mediated by other variables, and how the combination of different EEG abnormalities influences the complex outcome of schizophrenia. Objectives: The purpose of the study was to find EEG patterns which can predict the outcome of schizophrenia and identify recovered patients. Methods: Illness-related and functioning-related variables were measured in 61 SCZ at baseline and after four-years follow-up. EEGs were recorded at the baseline in resting-state condition and during two auditory tasks. We performed Sparse Partial Least Square (SPLS) Regression, using EEG features, age and illness duration to predict clinical and functional features at baseline and follow up. Through a Linear Support VectorMachine (Linear SVM) we used electrophysiological and clinical scores derived fromSPLS regression, in order to classify recovered patients at follow-up. Results: We found one significant latent variable (p<0.01) capturing correlations between independent and dependent variables at follow-up (RHO=0.56). Among individual predictors, age and illness-duration showed the highest scores; however, the score for the combination of the EEG features was higher than all other predictors. Within dependent variables, negative symptoms showed the strongest correlation with predictors. Scores resulting from SPLS Regression classified recovered patients with 90.1% of accuracy. Conclusions: A combination of electrophysiological markers, age and illness-duration might predict clinical and functional outcome of schizophrenia after 4 years of follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Different electrophysiological indices have been investigated to identify diagnostic and prognostic markers of schizophrenia (SCZ). However, these indices have limited use in clinical practice, since both specificity and association with illness outcome remain unclear. In recent years, machine learning techniques, through the combination of multidimensional data, have been used to better characterize SCZ and to predict illness course. Objectives: The aim of the present study is to identify multimodal electrophysiological biomarkers that could be used in clinical practice in order to improve precision in diagnosis and prognosis of SCZ. Methods: Illness-related and functioning-related variables were measured at baseline in 113 subjects with SCZ and 57 healthy controls (HC), and after four-year follow-up in 61 SCZ. EEGs were recorded at baseline in resting-state condition and during two auditory tasks (MMN-P3a and N100-P3b). Through a Linear Support Vector Machine, using EEG data as predictors, four models were generated in order to classify SCZ and HC. Then, we combined unimodal classifiers' scores through a stacking procedure. Pearson's correlations between classifiers score with illness-related and functioning-related variables, at baseline and follow-up, were performed. Results: Each EEG model produced significant classification (p < 0.05). Global classifier discriminated SCZ from HC with accuracy of 75.4% (p < 0.01). A significant correlation (r=0.40, p=0.002) between the global classifier scores with negative symptoms at follow-up was found. Within negative symptoms, blunted affect showed the strongest correlation. Conclusions: Abnormalities in electrophysiological indices might be considered trait markers of schizophrenia. Our results suggest that multimodal electrophysiological markers might have prognostic value for negative symptoms. [ABSTRACT FROM AUTHOR]

Introduction: The intestinal microbiota has been indicated to have a role in the pathophysiology of AN. Objectives: Aim of this study was to analyze fecal microbiome profiles of AN women before and after weight restoration and to combine them with fecal metabolomic profiles according to a multi-omics approach. Methods: The gut microbiome and fecal metabolites were characterized in 21 underweight AN women and after weight restoration and compared with those of 20 healthy women. Microbiome data were correlated with the relevant fecal metabolites. Results: AN subjects showed a decreased intra-individual bacterial richness, an increased Bacteroidetes-to-Firmicutes abundance ratio and significant changes in the relative abundances of several bacteria at different order levels in both the underweight and weight-restored condition compared to healthy women. The untargeted metabolomic procedure allowed the characterization of 224 metabolites involved in energy, lipid and amino acid metabolism. A genetic algorithm identified 49 relevant metabolites. The relationships among these fecalmetabolites and bacteria genera showed structures of different complexity in the 3 groups. In particular, a quarter of those relationships showed a divergent direction in the acute phase of AN than in the weight-restored phase or normal controls. Finally, in acute AN 70% of those correlations showed a negative sign suggesting a prevalent metabolites consummation by gut microbiome. Conclusions: Our results provide a picture of the connections between gut bacteria and fecal metabolites in both the acute phase of AN and after short-term weight restoration. Further studies should aim to investigate the significance of gut microbiome perturbations in development and treatment of AN. [ABSTRACT FROM AUTHOR]

Introduction: Alexithymia, that is the inability to recognize and describe one's own emotions, is a transdiagnostic feature across eating disorders (EDs) and it has been associated to a prolonged stress exposure. Objectives: Therefore, we evaluated whether alexithymia affects the hypothalamus-pituitary-adrenal (HPA) axis functioning in patients with anorexia nervosa (AN) or bulimia nervosa (BN). Methods: Twenty-six women with AN and 26 with BN participated in the study. Alexithymia was evaluated by the Toronto Alexithymia Scale-20 and eating-related psychopathology was measured by the Eating Disorder Inventory-2. The activity of the HPA axis was assessed by the salivary cortisol awakening response (CAR). Group differences in saliva CAR were tested by repeated measures 3-way ANOVA with diagnosis and alexithymia as between-subject factors. Results: The prevalence of alexithymia did not differ significantly between the two diagnostic groups (c2=1.24, p=0.26). Alexithymia was associated with more severe eating-related psychopathology in AN women but not in BN women. A significant reduction in the magnitude of CAR occurred in alexithymic patients with BN compared to non-alexithymic patients with BN (t = 3.39, p = 0.008), but not in alexithymic women with AN (t = 0.67, p = 0.54). Conclusions: These results confirm the presence of a more severe eating-related psychopathology in alexithymic individuals with AN and show, for the first time, an association between alexithymia and a dampened basal activity of the HPA axis in BN. [ABSTRACT FROM AUTHOR]

Introduction: Although the 5th Body Mass Index (BMI) percentile has been indicated by the DSM-5 in order to identify underweight in children and adolescents and to diagnose anorexia nervosa (AN), the validity of this cut-off has not been proved. Objectives: Aim of this study was to compare general and specific psychopathology between adolescents affected by AN with a BMI above or below the 5th percentile in order to test the validity of this weight cut-off. Methods: Four hundred-three adolescents with AN were recruited. They completed the Eating Disorder Inventory-3 (EDI-3) and the Youth Self Report (YSR). The sample was divided in two groups: below the 5th (n = 172) and above the 5th (n = 231). Quantitative differences between groups were investigated through t-test for independent samples. A network analysis was conducted in each group. Results: The group with BMI above the 5th percentile showed significantly higher scores in drive to thinness, body dissatisfaction, bulimia, personal and interpersonal alienation, social insecurity and asceticism. No significant differences emerged in general psychopathology measured through the YSR and in the occurrence of comorbidity between the groups. The group with BMI under the 5th percentile had a longer illness duration. No difference emerged between the network structure of the two groups. Conclusions: These findings suggest that the clinical utility of the 5th BMI percentile as weight cut-off for diagnosis of AN in children and adolescents is questionable. Indeed, it may prevent early illness detection and intervention, which are essential to improve treatment outcome. [ABSTRACT FROM AUTHOR]

Introduction Family members of patients with EDs report high levels of burden, psychological distress and the need to receive information on the disease of their ill relative. There is the need to provide family members and patients with psychoeducational family intervention in order to satisfy their care needs. Objective To develop a new psychoeducational approach for patients with Eating Disorders (EDs) and their relatives according to the Falloon model. Aims (1) To develop a family psychoeducational intervention for patients with EDs. (2) To implement the experimental intervention in the clinical routine care. (3) To evaluate efficacy of the approach in terms of reduction of family burden and improvement of relatives’ coping strategies. Results The Department of Psychiatry of the University of Naples SUN has developed a new psychoeducational family intervention for patients with EDs and their family members. The intervention consists of 6 sessions, scheduled weekly. The sessions deal with several topics such as information on EDs (e.g., causes, symptoms, clinical characteristics), communication skills (e.g., how to express an unpleasant feeling) and problem solving skills. The intervention is led by trained mental health professionals, such as psychiatrists, psychologists or rehabilitation technicians. Discussion This is the first example of psychoeducational intervention for families of patients with EDs developing according to the Falloon approach. Conclusions Family intervention represents an essential tool to provide to patients with EDs and their family members in order to promote a global recovery. [ABSTRACT FROM AUTHOR]

Introduction Anorexia nervosa (AN) is characterized by dysregulated eating that leads to chronic malnutrition, which may be responsible for several physical complications, including endocrine alterations, such as hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis. Objectives Several studies have shown a dysregulation of the cortisol awakening response (CAR) in symptomatic AN patients. However, it has not been established if the deranged CAR of underweight AN patients is a primary phenomenon or an alteration secondary to malnutrition. Aims The aim of this study was to explore the salivary CAR in both underweight and weight-restored patients with AN. Methods We recruited 59 women: 18 undernourished AN patients, 15 weight-restored AN women and 26 normal-weight healthy controls. Saliva samples were collected in the morning, immediately after awakening and after 15, 30 and 60 minutes, in order to measure saliva levels of cortisol. Participants filled in the state-trait anxiety inventory (STAI) to test their anxiety levels in the morning of the test. Results Compared to healthy controls, underweight AN patients showed an enhanced CAR whereas the weight recovered patients had a normal CAR. These results were not correlated with levels of anxiety. Conclusions For the first time, our results demonstrate that the deranged CAR found in acute AN patients is not present in weight-restored ones, suggesting that altered activity of the HPA axis of symptomatic AN patients is a state-dependent phenomenon. [ABSTRACT FROM AUTHOR]