Serum profiling of anorexia nervosa: A 1H NMR-based metabolomics study

Alireza Salehi M,Ida Ak Nilsson,João Figueira,Laura M Thornton,Israa Abdulkarim,Erik Pålsson,Cynthia M Bulik,Mikael Landén

doi:10.1016/j.euroneuro.2021.02.015

Abstract

Our understanding of pathophysiological mechanisms underlying anorexia nervosa (AN) is incomplete. The aim was to conduct a metabolomics profiling of serum samples from women with AN (n = 65), women who have recovered from AN (AN-REC, n = 65), and age-matched healthy female controls (HC, n = 65). Serum concentrations of 21 metabolites were measured using proton nuclear magnetic resonance (1H NMR). We used orthogonal partial least-squares discriminant analysis (OPLS-DA) modeling to assign group classification based on the metabolites. Analysis of variance (ANOVA) was used to test for metabolite concentration differences across groups. The OPLS-DA model could distinguish between the AN and HC groups (p = 9.05 × 10–11 R2Y = 0.36, Q2 = 0.37) and between the AN-REC and HC groups (p = 8.47 × 10–6, R2Y = 0.36, Q2 = 0.24,), but not between the AN and AN-REC groups (p = 0.63). Lower methanol concentration in the AN and AN-REC group explained most of the variance. Likewise, the strongest finding in the univariate analyses was lower serum methanol concentration in both AN and AN-REC compared with HC, which withstood adjustment for body mass index (BMI). We report for the first time lower serum concentrations of methanol in AN. The fact that low methanol was also found in recovered AN suggests that low serum concentration of methanol could either be trait marker or a scar effect of AN.

Highlights

Anorexia nervosa (AN) is a serious psychiatric disorder characterized by severe weight reduction or failure to achieve expected weight gains associated with extreme food restriction and/or energy expenditure with or without the presence of binge/purging behavior (Biomarkers Definitions Working, 2001; Treasure et al, 2015; Zipfel et al, 2015)
The loading plots (Figs. 1 and 2) show that lower methanol in AN and AN-REC compared with healthy controls (HC) explained most of the variance in the respective model
The orthogonal partial least-squares discriminant analysis (OPLS-DA) multivariate modeling failed to yield a significant classification between AN patients and AN-REC

Summary

Introduction

Anorexia nervosa (AN) is a serious psychiatric disorder characterized by severe weight reduction or failure to achieve expected weight gains associated with extreme food restriction and/or energy expenditure with or without the presence of binge/purging behavior (Biomarkers Definitions Working, 2001; Treasure et al, 2015; Zipfel et al, 2015). Adolescent girls and young women are at highest risk for developing the disorder (Zipfel et al, 2015), which is often associated with other psychiatric comorbidities such as anxiety or mood disorders (Boraska et al, 2014; Ulfvebrand et al, 2015). Duration of illness is typically protracted with around 30% of affected individuals achieving full recovery and about 25% developing a chronic course (Fichter et al, 2017; Warrier et al, 2018). A recent genome wide association study identified eight genome-wide significant loci and reported significant genetic correlations with both psychiatric traits and metabolic traits, encouraging a rebranding of AN as a metabo-psychiatric disorder (Watson et al, 2019)

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Results

Conclusion