New Insights in Anorexia Nervosa.
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ABSTRACT:
SUBMITTER: Gorwood P
PROVIDER: S-EPMC4925664 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
New Insights in Anorexia Nervosa.
Gorwood Philip P Blanchet-Collet Corinne C Chartrel Nicolas N Duclos Jeanne J Dechelotte Pierre P Hanachi Mouna M Fetissov Serguei S Godart Nathalie N Melchior Jean-Claude JC Ramoz Nicolas N Rovere-Jovene Carole C Tolle Virginie V Viltart Odile O Epelbaum Jacques J
Frontiers in neuroscience 20160629
Anorexia nervosa (AN) is classically defined as a condition in which an abnormally low body weight is associated with an intense fear of gaining weight and distorted cognitions regarding weight, shape, and drive for thinness. This article reviews recent evidences from physiology, genetics, epigenetics, and brain imaging which allow to consider AN as an abnormality of reward pathways or an attempt to preserve mental homeostasis. Special emphasis is put on ghrelino-resistance and the importance of ...[more]
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Project description:Anorexia nervosa (AN) is a psychiatric disorder with an estimated heritability of around 70%. Although the largest genome-wide association study meta-analysis on AN identified independent loci-conferring risk to the disorder, the molecular mechanisms underlying the genetic basis of AN remains to be elucidated. To explore AN, we ran a transcriptome profiling in peripheral blood mononuclear cells of 15 AN subjects and 15 healthy controls. We validated our mean results in a mouse model of chronic food restriction mimicking several aspects of AN. Through this exploratory study we identified 673 significantly differentially expressed genes in AN. Among these genes, we identified the Vanin-1 (Vnn1) gene that appears to play a major role in the regulation of multiple metabolic pathways. We confirmed an underexpression of Vnn1, especially in the liver, in a mouse model of chronic food restriction. These results indicate that quantitative food restriction affects Vnn1 expression, suggesting that this gene may contribute to the anorexic phenotype in the chronic food restriction mouse model as well as in patients affected by AN. We believe that this report highlights promising candidate genes and gene pathways for AN and reveals Vnn1 as a biomarker that may be used as molecular targets to predict and/or to understand AN.
2023-10-31 | GSE245978 | GEO
Project description:VNN1 : a new biomarker of anorexia nervosa
| PRJNA1030915 | ENA
Project description:Anorexia nervosa (AN) is a complex and multifactorial disorder occurring predominantly in women. Despite having the highest mortality among psychiatric conditions, it still lacks robust and effective treatment. Disorders such as AN are most likely syndromes with multiple genetic contributions, however, genome-wide studies have been underpowered to reveal associations with this uncommon illness. Here, we generated induced pluripotent stem cells (iPSCs) from adolescent females with AN and unaffected controls. These iPSCs were differentiated into neural cultures and subjected to extensive transcriptome analysis. Within a small cohort of patients who presented for treatment, we identified a novel gene that appears to contribute to AN pathophysiology, TACR1 (tachykinin 1 receptor). The participation of tachykinins in a variety of biological processes and their interactions with other neurotransmitters suggest novel mechanisms for how a disrupted tachykinin system might contribute to AN symptoms. Although TACR1 has been associated with psychiatric conditions, especially anxiety disorders, we believe this report is its first association with AN. Moreover, our human iPSC approach is a proof-of-concept that AN can be modeled in vitro with a full human genetic complement, and represents a new tool for understanding the elusive molecular and cellular mechanisms underlying the disease.
| S-EPMC5416680 | biostudies-literature
Project description:As part of the Genetic Consortium for Anorexia Nervosa (GCAN) and Wellcome Trust Case
Control Consortium 3 (WTCCC3), we have amassed the largest anorexia nervosa (AN)
sample in the world (~4,000). Following the WTCCC3 GWAS, we secured funding from the
Klarman Family Foundation to extend the genetic analyses to variants on the exome chip
(CoreExome array). This pre-lim relates to carrying out genotyping on the CoreExome array
on up to a maximum of 580 new samples.
| EGAS00001000913 | EGA
Project description:Anorexia nervosa (AN) is a complex debilitating disease characterized by intense fear of weight gain and excessive exercise. It is the deadliest of any psychiatric disorder with a high rate of recidivism, yet its pathophysiology is unclear. The Activity-Based Anorexia (ABA) paradigm is a widely accepted mouse model of AN that recapitulates hypophagia and hyperactivity despite reduced body weight, however, not the chronicity. Here, we modified the prototypical ABA paradigm to increase the time to lose 25% of baseline body weight from less than 7 days to more than 2 weeks. We used this paradigm to identify persistently altered genes after weight restoration that represent a metabolic memory of under-nutrition and may contribute to AN relapse. We focused on adipose tissue as it was identified as a major location of metabolic memory of over-nutririon. We identified 300 persistently dysregulated genes, including Calm2 and Vps13d, which could be potential global regulators of metabolic memory in both chronic over- and under-nutrition. However, despite being on the opposite spectrum of weight perturbations, the majority of metabolic memory genes of under- and over-nutrition do not overlap, suggestive of the different mechanisms involved in these extreme nutritional statuses.
2023-08-23 | GSE229316 | GEO
Project description:ImportanceThe COVID-19 pandemic has had considerable mental health consequences for children and adolescents, including the exacerbation of previously diagnosed eating disorders. Whether the pandemic is a factor associated with the concomitant increase in new-onset anorexia nervosa or atypical anorexia nervosa remains unknown.ObjectiveTo assess the incidence and severity of newly diagnosed anorexia nervosa or atypical anorexia nervosa in a national sample of youth before and during the first wave of the COVID-19 pandemic.Design, setting, and participantsThis repeated cross-sectional study analyzed new eating disorder assessments that were conducted at 6 pediatric tertiary-care hospitals in Canada between January 1, 2015, and November 30, 2020. Patients aged 9 to 18 years with a new anorexia nervosa or atypical anorexia nervosa diagnosis at the index assessment were included.ExposuresCOVID-19-associated public health confinement measures during the first wave of the pandemic (March 1 to November 30, 2020).Main outcomes and measuresPrimary outcomes were the incidence and hospitalization rates within 7 days of de novo anorexia nervosa or atypical anorexia nervosa diagnosis. Event rate trends during the first wave were compared with trends in the 5-year prepandemic period (January 1, 2015, to February 28, 2020) using an interrupted time series with linear regression models. Demographic and clinical variables were compared using a χ2 test for categorical data and t tests for continuous data.ResultsOverall, 1883 children and adolescents with newly diagnosed anorexia nervosa or atypical anorexia nervosa (median [IQR] age, 15.9 [13.8-16.9] years; 1713 female patients [91.0%]) were included. Prepandemic anorexia nervosa or atypical anorexia nervosa diagnoses were stable over time (mean [SD], 24.5 [1.6] cases per month; β coefficient, 0.043; P = .33). New diagnoses increased during the first wave of the pandemic to a mean (SD) of 40.6 (20.1) cases per month with a steep upward trend (β coefficient, 5.97; P < .001). Similarly, hospitalizations for newly diagnosed patients increased from a mean (SD) of 7.5 (2.8) to 20.0 (9.8) cases per month, with a significant increase in linear trend (β coefficient, -0.008 vs 3.23; P < .001). These trends were more pronounced in Canadian provinces with higher rates of COVID-19 infections. Markers of disease severity were worse among patients who were diagnosed during the first wave rather than before the pandemic, including more rapid progression (mean [SD], 7.0 [4.2] months vs 9.8 [7.4] months; P < .001), greater mean (SD) weight loss (19.2% [9.4%] vs 17.5% [9.6%]; P = .01), and more profound bradycardia (mean [SD] heart rate, 57 [15.8] beats per minute vs 63 [15.9] beats per minute; P < .001).Conclusions and relevanceThis cross-sectional study found a higher number of new diagnoses of and hospitalizations for anorexia nervosa or atypical anorexia nervosa in children and adolescents during the first wave of the COVID-19 pandemic in Canada. Research is needed to better understand the drivers and prognosis for these patients and to prepare for their mental health needs in the event of future pandemics or prolonged social isolation.
| S-EPMC8652595 | biostudies-literature
Project description:ObjectiveAntidiuretic hormone (ADH) is involved in the response to stress and in depression and anxiety. However, studies on ADH in anorexia nervosa (AN) show conflicting results. A major reason for this may be methodological challenges due to short half-life of ADH in circulation and rapid degradation in vitro. To overcome these obstacles, copeptin, the C-terminal fragment stemming from the ADH precursor, has been increasingly used as a stable clinical measure for ADH. Furthermore, copeptin has been recognized as a biomarker of insulin resistance in obesity.MethodsWe measured fasting copeptin in plasma from 25 normohydrated, stable women with AN (BMI 13.0 ± 2.0) and 25 age-matched women.ResultsNo difference in copeptin levels was found (6.8 ± 1.8 vs. 5.5 ± 0.5 pmol/L). Confirmatory, copeptin concentrations were correlated to insulin resistance assessed by the homeostasis model assessment of insulin resistance.DiscussionWe report for the first time that copeptin level as a marker of ADH activity is not altered in fluid- and electrolyte-stabilized patients with severe AN patients, indicating that ADH may not be crucial in the pathophysiological involvement of psychologic stress in AN.
| S-EPMC7177552 | biostudies-literature
Project description:Purpose of reviewGenetic factors contribute to the etiology of anorexia nervosa (AN). This review synthesizes the current state of knowledge about the genetic etiology of AN, provides directions for future research, and discusses clinical implications for this research.Recent findingsCandidate gene meta-analyses indicate serotonin genes may be involved in the genetic etiology of AN. Three genome-wide association studies have been conducted and one genome-wide significant locus was identified. Cross-disorder analyses suggest shared genetic risk between AN and several psychiatric, educational, and medical phenotypes. Much has been learned about the genetic etiology of AN over the past 3 decades. However, to fully understand the genetic architecture, we must consider all aspects including common variation, cross-disorder analysis, rare variation, copy number variation, and gene-environment interplay. Findings have important implications for the development of treatment and prevention approaches and for how AN, and psychiatric and medical diseases in general, are conceptualized.
| S-EPMC6139670 | biostudies-literature
Project description:Anorexia nervosa (AN) has the highest mortality rate of any psychiatric disease, yet available pharmacological treatments are largely ineffective due, in part, to an inadequate understanding of the neurobiological drivers that underpin the condition. The recent resurgence of research into the clinical applications of psychedelic medicine for a range of mental disorders has highlighted the potential for classical psychedelics, including psilocybin, to alleviate symptoms of AN that relate to serotonergic signaling and cognitive inflexibility. Clinical trials using psychedelics in treatment-resistant depression have shown promising outcomes, although these studies are unable to circumvent some methodological biases. The first clinical trial to use psilocybin in patients with AN commenced in 2019, necessitating a better understanding of the neurobiological mechanisms through which psychedelics act. Animal models are beneficial in this respect, allowing for detailed scrutiny of brain function and behavior and the potential to study pharmacology without the confounds of expectancy and bias that are impossible to control for in patient populations. We argue that studies investigating the neurobiological effects of psychedelics in animal models, including the activity-based anorexia (ABA) rodent model, are particularly important to inform clinical applications, including the subpopulations of patients that may benefit most from psychedelic medicine.
| S-EPMC7015070 | biostudies-literature
Project description:BackgroundLittle is known about the long-term outcome of anorexia nervosa.AimsTo study the 30-year outcome of adolescent-onset anorexia nervosa.MethodAll 4291 individuals born in 1970 and attending eighth grade in 1985 in Gothenburg, Sweden were screened for anorexia nervosa. A total of 24 individuals (age cohort for anorexia nervosa) were pooled with 27 individuals with anorexia nervosa (identified through community screening) who were born in 1969 and 1971-1974. The 51 individuals with anorexia nervosa and 51 school- and gender-matched controls were followed prospectively and examined at mean ages of 16, 21, 24, 32 and 44. Psychiatric disorders, health-related quality of life and general outcome were assessed.ResultsAt the 30-year follow-up 96% of participants agreed to participate. There was no mortality. Of the participants, 19% had an eating disorder diagnosis (6% anorexia nervosa, 2% binge-eating disorder, 11% other specified feeding or eating disorder); 38% had other psychiatric diagnoses; and 64% had full eating disorder symptom recovery, i.e. free of all eating disorder criteria for 6 consecutive months. During the elapsed 30 years, participants had an eating disorder for 10 years, on average, and 23% did not receive psychiatric treatment. Good outcome was predicted by later age at onset among individuals with adolescent-onset anorexia nervosa and premorbid perfectionism.ConclusionsThis long-term follow-up study reflects the course of adolescent-onset anorexia nervosa and has shown a favourable outcome regarding mortality and full symptom recovery. However, one in five had a chronic eating disorder.
| S-EPMC7557598 | biostudies-literature