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Journal of psychiatry & neuroscience : JPN
2025 Mar-Apr;50 (2): E85-E91.

Elevated plasma B and betaine levels in women with anorexia nervosa: possible role in illness pathophysiology and epigenetic regulation.

Howard Steiger, Kevin F Casey, Jessica Burdo, Valerie Marcil, Maegan Harvison, Juliana Meyerfreund, Édith Breton, Zsofia Nemoda, Lea Thaler, Annie St-Hilaire, Mimi Israel, Chloe Paquin-Hodge, Luis B Agellon, Véronique Bélanger, Linda Booij
Author Information
  1. Howard Steiger: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon) stehow@douglas.mcgill.ca.
  2. Kevin F Casey: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  3. Jessica Burdo: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  4. Valerie Marcil: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  5. Maegan Harvison: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  6. Juliana Meyerfreund: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  7. Édith Breton: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  8. Zsofia Nemoda: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  9. Lea Thaler: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  10. Annie St-Hilaire: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  11. Mimi Israel: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  12. Chloe Paquin-Hodge: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  13. Luis B Agellon: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  14. Véronique Bélanger: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
  15. Linda Booij: From the Eating Disorders Continuum, Douglas Institute, Montréal, Que. (Steiger, Casey, Harvison, Meyerfreund, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Douglas Institute Research Centre, Montréal, Que. (Steiger, Casey, Harvison, Nemoda, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychiatry, McGill University, Montréal, Que. (Steiger, Harvison, Thaler, St-Hilaire, Israel, Paquin-Hodge, Booij); the Department of Psychology, Toronto Metropolitan University, Toronto, Ont. (Burdo); the Research Centre, Sainte-Justine University Hospital Centre (Marcil, Bélanger, Booij) Montréal, Que.; Department of Nutrition, Université de Montréal, Montréal, Que. (Marcil, Bélanger); the Department of Basic Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que. (Breton); the School of Human Nutrition, McGill University, Montréal, Que. (Agellon).
PMID: 40037661 DOI: 10.1503/jpn.240155

Abstract

BACKGROUND: Phenomenology in anorexia nervosa (AN) appears to be subject to epigenetic regulation via DNA methylation. The micronutrients B and betaine contribute directly to DNA methylation and have been shown to be abnormally elevated in blood samples from people with AN.
METHODS: We measured plasma B and betaine levels, as well as leukocyte DNA methylation levels, among women with active AN (AN-active group), those in 1-year remission from AN (AN-remitted group), and those who had never experienced an eating disorder (NED group). We compared the groups on micronutrient levels and on the strength of association between micronutrients and methylation.
RESULTS: We included 64 women in the AN-active group, 49 in the AN-remitted group, and 49 in the NED group. Relative to those with NED (B: mean 339.6 [standard deviation (SD) 224.3] μmol/L; betaine: mean 33.74 [SD 17.10] μmol/L), participants with active AN showed high B and betaine (B: mean 571.0 [SD 505.2] μmol/L; betaine: mean 43.73 [SD 22.50] μmol/L); AN-remitted participants had elevated B alone (B: mean 588.2 [SD 379.9] μmol/L; betaine: mean 33.50 [SD 19.20] μmol/L). There were also group-based differences in the strength of association between B and site-specific DNA methylation at genes regulating insulin function, glucose metabolism, cell regulation, and neurotransmitter function. These associations between B and methylation levels were generally stronger among those without an ED than among those with either active or remitted AN.
LIMITATIONS: The extent to which plasma nutrient levels provide a meaningful proxy to cellular processes affecting DNA methylation is uncertain and the sample size limits the stability of results. We included only biological females in this investigation.
CONCLUSION: Elevated B levels in AN resemble elevations reported among people with autoimmune, neoplastic, or other disorders. Such elevations imply that plasma B levels may misrepresent nutritional status among people with AN. Observed associations between levels of B and methylation at certain gene regions have ambiguous importance, but may indicate an influence of nutritional status on epigenetic mechanisms or may be the coincidence of separate processes that independently affect levels of micronutrients and DNA methylation.

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MeSH Term

Humans
Betaine
Female
Anorexia Nervosa
Epigenesis, Genetic
Vitamin B 12
DNA Methylation
Adult
Young Adult
Leukocytes
Adolescent

Chemicals

Betaine
Vitamin B 12
Journal Article

Word Cloud

Created with Highcharts 10.0.0BlevelsmethylationANDNAgroupmeanμmol/Lamong[SDbetaineplasmaepigeneticregulationmicronutrientspeoplewomenactiveAN-remittedNEDB:betaine:mayanorexiaelevatedAN-activestrengthassociationincluded4933participantsfunctionassociationsprocessesElevatedelevationsnutritionalstatusBACKGROUND:PhenomenologynervosaappearssubjectviacontributedirectlyshownabnormallybloodsamplesMETHODS:measuredwellleukocyte1-yearremissionneverexperiencedeatingdisordercomparedgroupsmicronutrientRESULTS:64Relative3396[standarddeviationSD2243]741710]showedhigh57105052]43732250]alone58823799]501920]alsogroup-baseddifferencessite-specificgenesregulatinginsulinglucosemetabolismcellneurotransmittergenerallystrongerwithoutEDeitherremittedLIMITATIONS:extentnutrientprovidemeaningfulproxycellularaffectinguncertainsamplesizelimitsstabilityresultsbiologicalfemalesinvestigationCONCLUSION:resemblereportedautoimmuneneoplasticdisordersimplymisrepresentObservedcertaingeneregionsambiguousimportanceindicateinfluencemechanismscoincidenceseparateindependentlyaffectnervosa:possibleroleillnesspathophysiology

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