Inverse association of circulating SIRT1 and adiposity. A study on underweight, normal weight, and obese patients

Context: Sirtuins (SIRTs) are NAD+-dependent deacetylases, cellular sensors to detect energy availability, and modulate metabolic processes. SIRT1, the most studied family member, influences a number of tissues including adipose tissue. Expression and activity of SIRT1 reduce with weight gain and increase in conditions of starvation. Objective: To focus on SIRT1 plasma concentrations in different conditions of adiposity and to correlate SIRT1 with fat content and distribution, energy homeostasis and inflammation in under-weight, normal-weight, and obese individuals. Materials and Methods: 21 patients with anorexia nervosa, 26 normal-weight and 75 patients with obesity were evaluated. Body fat composition by dual-energy X-ray absorptiometry, ultrasound liver adiposity, echocardiographic epicardial fat thickness (EFT), inflammatory (ESR, CRP, and fibrinogen), and metabolic (FPG, insulin, LDL- and HDL-cholesterol, triglycerides) parameters, calculated basal metabolic rate (BMR) and plasma SIRT1 (ELISA) were measured. Results: SIRT1 was significantly higher in anorexic patients compared to normal-weight and obese patients (3.27 ± 2.98, 2.27 ± 1.13, and 1.36 ± 1.31 ng/ml, respectively). Linear regression models for each predictor variable adjusted for age and sex showed that SIRT1 concentration was inversely and significantly correlated with EFT, fat mass %, liver fat content, BMR, weight, BMI, WC, LDL-cholesterol, insulin, ESR. Stepwise multiple regression analysis revealed that age and EFT were the best independent correlates of SIRT1 (β = -0.026 ± 0.011, p = 0.025, and β = -0.516 ± 0.083, p < 0.001, respectively). Conclusions: Plasma SIRT1 shows a continuous pattern that inversely follows the whole spectrum of adiposity. SIRT1 significantly associates with EFT, a strong index of visceral fat phenotype, better than other indexes of adiposity studied here

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

REATTIVITÀ VAGALE IN RISPOSTA A STIMOLI APPETITIVI E NEUTRI IN SOGGETTI CON DIAGNOSI DI OBESITA’

L’obesità è caratterizzata da anomala assunzione di cibo e da eccessivo accumulo di grasso. Il comportamento alimentare è dipendente dall’osservazione di stimoli come il cibo. Un indice particolarmente adatto per studiare la risposta a questi stimoli nei disturbi del comportamento alimentare è la variabilità del battito cardiaco, un parametro di funzionamento del sistema nervoso parasimpatico in grado di riflettere la capacità di regolare le emozioni e di inibire comportamenti disfunzionali. Questo studio si propone di esplorare la variabilità del battito cardiaco alla presentazione di immagini legate al cibo in un gruppo di pazienti obesi e in soggetti normopeso. Si ipotizza che, per i soli pazienti, gli stimoli legati al cibo diventino ansiogeni e scatenino una risposta fisiologica di crollo vagale. Si ipotizza inoltre che questo non si verifichi di fronte a stimoli non legati al cibo. 24 pazienti obesi ricoverati (19 femmine; età: 49.20 ± 13.64; indice di massa corporea: 41.63 ± 8.09) e 37 soggetti normopeso (24 femmine; età: 25.08 ± 6.76; indice di massa corporea: 22.14 ± 2.74) sono stati sottoposti a monitoraggio elettrocardiografico durante una condizione di riposo (baseline), un compito sperimentale e una fase di recupero. Un sottogruppo di pazienti (n = 11) ha ripetuto il paradigma sostituendo gli stimoli legati al cibo con stimoli neutri (oggetti). I risultati mostrano una riduzione significativa della variabilità interbattito dei pazienti, ma non dei controlli (p < .05), di fronte al cibo. Inoltre, i pazienti mostrano un’incapacità di ritornare ai valori di base al termine del compito (attivazione fisiologica sostenuta; p < .05). Come previsto, di fronte a stimoli neutri, i pazienti non mostrano alcuna risposta di attivazione fisiologica (n.s.). I risultati confermano la relazione tra aspetti fisiologici e psicologici nei disturbi alimentari e giustificano future indagini sulla reattività del sistema nervoso autonomo a stimoli salienti in persone obese

Obesity is associated with lack of inhibitory control and impaired heart rate variability reactivity and recovery in response to food stimuli

Recent theories compare obesity with addiction in terms of lack of inhibitory control in both clinical populations. The present study hypothesized impaired inhibition in obese patients reflected both in executive functions and reduced vagal tone (indexed by a decrease in heart rate variability; HRV) in response to food stimuli. Twenty-four inpatients with obesity (19 women) and 37 controls (24 women) underwent ECG monitoring during baseline, food stimuli viewing, and a recovery phase. Tests and questionnaires assessing inhibitory control and psychopathological dispositions were also administered. As hypothesized, patients were characterized by deficits in all the tests measuring inhibitory capacities. Results also show greater HRV reduction and impaired HRV recovery in response to food stimuli in obese patients compared to controls. The drive to eat experienced by obese patients in the absence of caloric need may rely on impairments in inhibitory and vagal functioning. Results are discussed in terms of implications for therap

Psychopathology, body uneasiness and self-identity in patients with non-BED obesity compared to healthy controls

Introduction: Obesity represents a major public health problem associated with medical and psychological impairment. Obesity is frequently studied with Binge Eating Disorder (BED) comorbidity. Less evidence is available for non-BED obesity, in spite of its correlation with psychological impairment and body image disturbance. In this study, we explored psychopathological features, eating behaviors, body image disturbance and self-identity impairment in patients with obesity and a control group. In patients, we also studied the relation between specific eating/body features and psychopathological symptoms. Finally, we explored the latent factorial structure that describes these features. Material and methods: The clinical sample was composed by twenty patients suffering from obesity without BED (16 females). The control group included twenty-eight healthy and normal-weight subjects (20 females) enrolled from the general population. All participants underwent a clinical interview and filled out questionnaires about body image and psychopathological symptoms. Statistics: The Student t test was applied to compare obese patients and healthy controls in all psychological dimensions. In the clinical sample, gender differences were tested through multivariate analyses of variance (MANOVA). Then, correlational analyses explored the relation between specific eating/body features and psychopathological symptoms. Lastly, a principal-components factor analysis was performed to explore the existence of a latent factorial structure emerging from assessment evaluation in obese population. Results: Obese patients reported significantly higher scores than healthy controls in several psychopathological dimensions, i.e. Somatization, Obsessive-Compulsive, Depression, Hostility, Phobic Anxiety, and Psychoticism. Patients also reported higher body uneasiness and self-identity impairment resulting from some scores on Body Uneasiness Test and Identity and Eating Disorders questionnaire. Avoidant behaviours were more frequently reported in men whereas women reported higher body distress/dissatisfaction. In the clinical sample the questionnaires were correlated and a three-factor structure emerged: “Weight and body control”, “Weakness of Self-Identity”, and “Psychopathological distress”. Discussion: The present study found that obese patients might present several disturbances in body image, self- perception and general psychopathological distress. Clinicians should be aware of these issues to improve therapeutic strategy in the treatment of obesity

No differential effect of age on brain matter volume and cognition in bipolar patients and healthy individuals

Bipolar disorder (BD) is associated with brain structural and cognitive abnormalities. There is a paucity of evidence regarding the evolution of these deficits over time. This study examined the relationship between age and brain morphology and cognition in patients with BD type I. Brain structural magnetic resonance imaging data were acquired using a 1.5T scanner from 71 BD patients and 82 age- and gender-matched controls and analysed using Statistical Parametric Mapping. In addition, participants were evaluated using the Wechsler Adult Intelligence Scale, Revised; the Wechsler Memory Scale, third edition; the Hayling Sentence Completion Task, a measure of response inhibition; and the Wisconsin Card Sorting Test, which reflects rule discovery and perseveration. We found a significant effect of age but not of diagnosis and no age-by-diagnosis interaction in global gray and white matter and cerebrospinal fluid volumes. There was no differential effect of age on the two diagnostic groups with respect to cognitive task performance. Our findings do not support differential age-related changes in brain structure and cognition in patients with bipolar disorder compared to healthy individuals. Cross-sectional studies are, however, limited and longitudinal data will be required to further explore this issue

Additional file 1: of Cancer-related CD15/FUT4 overexpression decreases benefit to agents targeting EGFR or VEGF acting as a novel RAF-MEK-ERK kinase downstream regulator in metastatic colorectal cancer

Supplementary Tables S1-S4. (DOC 121 kb