Am J Med Genet B Neuropsychiatr Genet
December 2024
Anorexia nervosa (AN) is a psychiatric disorder with an estimated heritability of around 70%. Although the largest meta-analysis of genome-wide association studies on AN identified independent risk-conferring loci for the disorder, the molecular mechanisms underlying the genetic basis of AN remain to be elucidated. To investigate AN, we performed transcriptome profiling in peripheral blood mononuclear cells from 15 AN patients and 15 healthy controls.
View Article and Find Full Text PDFExtracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations.
View Article and Find Full Text PDFCholinergic striatal interneurons (ChIs) express the vesicular glutamate transporter 3 (VGLUT3) which allows them to regulate the striatal network with glutamate and acetylcholine (ACh). In addition, VGLUT3-dependent glutamate increases ACh vesicular stores through vesicular synergy. A missense polymorphism, VGLUT3-p.
View Article and Find Full Text PDFBackground: Anorexia nervosa (AN) is a severe psychiatric disorder associated with frequent relapses and variability in treatment responses. Previous literature suggested that such variability is influenced by premorbid vulnerabilities such as abnormalities of the reward system. Several factors may indicate these vulnerabilities, such as neurocognitive markers (tendency to favour delayed reward, poor cognitive flexibility, abnormal decision process), genetic and epigenetic markers, biological and hormonal markers, and physiological markers.
View Article and Find Full Text PDFBackground: Treatment of anorexia nervosa (AN) sometimes requires hospitalisation, which is often lengthy, with little ability to predict individual trajectory. Depicting specific profiles of treatment response and their clinical predictors could be beneficial to tailor inpatient management. The aim of this research was to identify clusters of weight recovery during inpatient treatment, and their clinical predictors.
View Article and Find Full Text PDFContext: The use of vagus nerve stimulation (VNS) to reduce or stop electroconvulsive therapy (ECT) in treatment-resistant depression seems promising. The aim of this study was to investigate the efficacy of VNS on the reduction of ECT sessions and mood stabilization.
Methods: We conducted a monocentric retrospective case series of patients who suffered from treatment-resistant depression, treated with ECT and referred to our center for VNS.
Objective: Circulating cell-free DNA (cfDNA) holds promise as a rapid and convenient biomarker for identifying individuals with eating disorders. To investigate this hypothesis, we measured plasma cfDNA in patients with different eating disorders.
Methods: In this study, 110 participants (98 patients with eating disorders divided into 30 patients with bulimia nervosa, 33 patients with anorexia nervosa (AN) Restricting subtype, 35 patients with AN Binge-eating/purging subtype and 12 controls) were enrolled.
Introduction: T cell expressed CD27 provides costimulation upon binding to inducible membrane expressed trimeric CD70 and is required for protective CD8 T cell responses. CD27 agonists could therefore be used to bolster cellular vaccines and anti-tumour immune responses. To date, clinical development of CD27 agonists has focussed on anti-CD27 antibodies with little attention given to alternative approaches.
View Article and Find Full Text PDFPurpose: The present study aimed to explore the implicit associations between food and bodily stimuli in patients with anorexia nervosa (AN) and control subjects (HC).
Methods: A Go/No-Go Association Task was administrated to 55 participants (28 AN and 27 HC), using food stimuli (low-calorie food vs. high-calorie food) and body stimuli (underweight vs.
LEAP-2 is a ghrelin antagonist with an anorexigenic drive. This study investigates the evolution of plasma ghrelin and LEAP-2 concentrations in 29 patients with anorexia nervosa (AN) before and after refeeding and compares it to physiological adaptations during fasting in healthy controls or to mouse model of chronic food restriction and refeeding. Acute and chronic food restriction decrease LEAP-2 and increase ghrelin concentrations in both humans and mice, while patients with AN displayed higher ghrelin and LEAP-2 concentrations before than after refeeding (p = 0.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
July 2023
Common mental disorders (CMDs) such as depression, anxiety and post-traumatic stress disorders account for 40% of the global burden of disease. In most psychiatric disorders, both diagnosis and monitoring can be challenging, frequently requiring long-term investigation and follow-up. The discovery of better methods to facilitate accurate and fast diagnosis and monitoring of psychiatric disorders is therefore crucial.
View Article and Find Full Text PDFEat Weight Disord
February 2023
Purpose: Qualitative food avoidance is a significant issue in patients with anorexia nervosa (AN) and restoring diet diversity is an important part of the treatment process. We aimed to identify clinical factors which drive food avoidance and predict its maintenance in patients with AN.
Methods: In this multicentre longitudinal study, 130 female outpatients with AN were assessed before and after 4 months of care in clinical centres specialized in AN.
The tumor suppressor protein p53 is inactivated in the majority of human cancers and remains a prime target for developing new drugs to reactivate its tumor suppressing activity for anticancer therapies. The oncogenic p53 mutant Y220C accounts for approximately 125,000 new cancer cases per annum and is one of the most prevalent p53 mutants overall. It harbors a narrow, mutationally induced pocket at the surface of the DNA-binding domain that destabilizes p53, leading to its rapid denaturation and aggregation.
View Article and Find Full Text PDFTapasin, a component of the major histocompatibility complex (MHC) I peptide loading complex, edits the repertoire of peptides that is presented at the cell surface by MHC I and thereby plays a key role in shaping the hierarchy of CD8+ T-cell responses to tumors and pathogens. We have developed a system that allows us to tune the level of tapasin expression and independently regulate the expression of competing peptides of different off-rates. By quantifying the relative surface expression of peptides presented by MHC I molecules, we show that peptide editing by tapasin can be measured in terms of "tapasin bonus," which is dependent on both peptide kinetic stability (off-rate) and peptide abundance (peptide supply).
View Article and Find Full Text PDFIntroduction: Body image distortion is a core symptom of anorexia nervosa (AN), embodying dissatisfaction and overvaluation of body appearance and weight. Body image distortion is an important factor in the maintenance of weight loss behaviours such as compulsive physical exercise. Conversely, physical exercise seems to have an aggravating effect on body image in patients with AN, but the evidence is still poor.
View Article and Find Full Text PDFObjectives: To describe the clinical and pathological features of biopsy-proven cutaneous vasculitis (CV) associated with SLE, focusing on diagnosis classification and impact on overall SLE activity.
Methods: Retrospective multicentric cohort study including SLE patients with biopsy-proven CV identified by (i) data from pathology departments of three university hospitals and (ii) a national call for cases. SLE was defined according to 1997 revised ACR and/or 2019 ACR/EULAR criteria.
Antibodies protect from infection, underpin successful vaccines and elicit therapeutic responses in otherwise untreatable cancers and autoimmune conditions. The human IgG2 isotype displays a unique capacity to undergo disulfide shuffling in the hinge region, leading to modulation of its ability to drive target receptor signaling (agonism) in a variety of important immune receptors, through hitherto unexplained molecular mechanisms. To address the underlying process and reveal how hinge disulfide orientation affects agonistic activity, we generated a series of cysteine to serine exchange variants in the hinge region of the clinically relevant monoclonal antibody ChiLob7/4, directed against the key immune receptor CD40.
View Article and Find Full Text PDFRecently, neurocognitive studies have shown that food categorization is sensitive to both the properties of the food stimuli (e.g., calorie content) and the individual characteristics of subjects (e.
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