Alessio Maria Monteleone

Bio: Alessio Maria Monteleone is an academic researcher from Seconda Università degli Studi di Napoli. The author has contributed to research in topics: Eating disorders & Bulimia nervosa. The author has an hindex of 23, co-authored 108 publications receiving 2191 citations. Previous affiliations of Alessio Maria Monteleone include King's College London & University of Naples Federico II.

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Abstract: Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

The impact of COVID-19 epidemic on eating disorders: A longitudinal observation of pre versus post psychopathological features in a sample of patients with eating disorders and a group of healthy controls.

Abstract: Objective the aim of this longitudinal study was to evaluate the impact of COVID-19 epidemic on Eating Disorders (EDs) patients, considering the role of pre-existing vulnerabilities. Method 74 patients with Anorexia Nervosa (AN) or Bulimia Nervosa (BN) and 97 healthy controls (HCs) were evaluated before lockdown (T1) and during lockdown (T2). Patients were also evaluated at the beginning of treatment (T0). Questionnaires were collected to assess psychopathology, childhood trauma, attachment style, and COVID-19-related post-traumatic symptoms. Results A different trend between patients and HCs was observed only for pathological eating behaviors. Patients experienced increased compensatory exercise during lockdown; BN patients also exacerbated binge eating. Lockdown interfered with treatment outcomes: the descending trend of ED-specific psychopathology was interrupted during the epidemic in BN patients. Previously remitted patients showed re-exacerbation of binge eating after lockdown. Household arguments and fear for the safety of loved ones predicted increased symptoms during the lockdown. BN patients reported more severe COVID-19-related post-traumatic symptomatology than AN and HCs, and these symptoms were predicted by childhood trauma and insecure attachment. Discussion COVID-19 epidemic significantly impacted on EDs, both in terms of post-traumatic symptomatology and interference with the recovery process. Individuals with early trauma or insecure attachment were particularly vulnerable.

Eating disorders: What age at onset?

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

Integrative analysis of 111 reference human epigenomes

Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

BRIEF COMMUNICATION ARISING: Gut hormone PYY3-36 physiologically inhibits food intake

Abstract: Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY3-36 (PYY3-36), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY3-36 in rats inhibits food intake and reduces weight gain. PYY3-36 also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY3-36 increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY3-36 inhibits food intake. PYY3-36 also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY3-36 significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut–hypothalamic pathway.

A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals

Abstract: The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

Changes in physical activity and sedentary behaviours from before to during the COVID-19 pandemic lockdown: a systematic review

Abstract: Objective In March 2020, several countries banned unnecessary outdoor activities during COVID-19, commonly called ‘lockdowns. These lockdowns have the potential to impact associated levels of physical activity and sedentary behaviour. Given the numerous health outcomes associated with physical activity and sedentary behaviour, the aim of this review was to summarise literature that investigated differences in physical activity and sedentary behaviour before vs during the COVID-19 lockdown. Design, data sources and eligibility criteria Electronic databases were searched from November 2019 to October 2020 using terms and synonyms relating to physical activity, sedentary behaviour and COVID-19. The coprimary outcomes were changes in physical activity and/or sedentary behaviour captured via device-based measures or self-report tools. Risk of bias was measured using the Newcastle-Ottawa Scale. Results Sixty six articles met the inclusion criteria and were included in the review (total n=86 981). Changes in physical activity were reported in 64 studies, with the majority of studies reporting decreases in physical activity and increases in sedentary behaviours during their respective lockdowns across several populations, including children and patients with a variety of medical conditions. Conclusion Given the numerous physical and mental benefits of increased physical activity and decreased sedentary behaviour, public health strategies should include the creation and implementation of interventions that promote safe physical activity and reduce sedentary behaviour should other lockdowns occur.