Review
Eating disorders, gene–environment interactions and epigenetics

https://doi.org/10.1016/j.neubiorev.2010.09.012Get rights and content

Abstract

This review describes the various subtypes of eating disorders and examines factors associated with the risk of illness. It considers evidence that the development and maintenance of eating disorders is due to gene–environment interactions (GxE) that alter genetic expression via epigenetic processes. It describes how environmental factors such as those associated with nutrition and/or stress may cause epigenetic changes which have transcriptional and phenotypic effects, which, in turn, alter the long term risk of developing an eating disorder. It reviews theoretical and practical issues associated with epigenetic studies in psychiatry and how these are relevant to eating disorders. It examines the limited number of epigenetic studies which have been conducted in eating disorders and suggests directions for further research. Understanding the relationship between epigenetic processes and the risk of an eating disorder opens possibilities for preventive and/or therapeutic interventions. For example, epigenetic changes associated with diet and weight may be reversible and those associated with cognitive processes may be accessible to pharmacological interventions.

Research highlights

▶ The risk of an eating disorder is part genetic and part environmental. ▶ The inherited risk involves many genes of small effect. ▶ Environmental factors include nutrition and stress. ▶ Gene environment interactions (GxE) are likely to be involved. ▶ The potential role and the investigation of epigenetics in the GxE is examined.

Section snippets

Eating disorders

Eating disorders (ED) encompass anorexia nervosa (AN), bulimia nervosa (BN), eating disorder not otherwise specified (EDNOS) and binge eating disorder (BED). Anorexia nervosa and bulimia nervosa typically affect young women and have a peripubertal onset: binge eating disorder occurs in both sexes and has a more varied onset (Hudson and Pope, Jr., 2007). Obesity is not classified as an eating disorder, but as eating disorders and obesity can occur simultaneously or sequentially in the same

Epigenetics

Epigenetic mechanisms regulate gene expression independently of DNA sequence. In most, but not all cases, they produce reversible changes in gene function by modifying DNA and associated histones and via the action of small non-coding RNA molecules (Dulac, 2010). Aberrant epigenetic processes have been linked to the aetiology of cancer (Baylin and Schuebel, 2007, Duman and Newton, 2007, Tsankova et al., 2007) but are also likely to contribute to the aetiology of numerous non-malignant complex

Do epigenetic modifications mediate the effects of stress in pregnancy and/or perinatal complications on the risk of eating disorder in the offspring?

Maternal stress during pregnancy has effects on neonatal outcomes, on childhood emotional and cognitive functioning, and on adult psychopathology (Talge et al., 2007). People with eating disorders have increased anxiety and anxiety disorders that predate the eating disorder (Raney et al., 2008, Swinbourne and Touyz, 2007) and persist to an extent after recovery (Wentz et al., 2009). When pregnant, women with current or past eating disorders are likely to be more anxious than other pregnant

Does nutrition in pregnancy alter the risk of an eating disorder in the offspring via epigenetic processes?

Women with current or past anorexia nervosa or bulimia nervosa have poorer obstetric outcomes (Blais et al., 2000, Ekeus et al., 2006, Micali et al., 2007b, Sollid et al., 2004). Fertility clinic attenders have high rates of eating disorders (Freizinger et al., 2008, Stewart et al., 1990) and treatment helps them conceive even at low weight. Pregnancy usually leads to symptom reduction or remission of pre-existing eating disorders (Micali et al., 2007b) but can be associated with new onsets (

Candidate genes for epigenetic studies in eating disorders

As stated above, biological factors associated with weight regulation and energy homeostasis may contribute to vulnerability to an eating disorder, to obesity and to some of their shared risk factors. There is an extensive literature on how gastrointestinal and energy sensing systems in the periphery interact with central loci especially in the hypothalamus (Luquet and Magnan, 2009, Pirnik et al., 2010, Smith and Ferguson, 2008, Wren, 2008) but also with higher brain areas (Batterham et al.,

Epigenetic changes associated with psychological processes: implications for eating disorders

Psychiatric comorbidity is common in eating disorders and they may share some susceptibility genes with mood, impulse control and substance misuse disorders (Hudson and Pope, 2007, Spindler and Milos, 2007). All of these problems are related to temperamental traits. People with eating disorders typically have a fear of food, eating and fatness which does not habituate even during prolonged treatment with regular meals. In individuals who are temperamentally anxious and whose emotion circuitry

Epigenetic research and eating disorders

Epigenetic studies of psychiatric/behavioural diseases, are relatively recent and methods are still being developed (Mill and Petronis, 2007). There have however, been some epigenetic studies in eating disorders. Significant global DNA hypomethylation has been found in lymphocytes from patients with anorexia nervosa, but not bulimia nervosa (Frieling et al., 2007). This included decreased expression of the alpha synuclein gene (SNCA) associated with hypermethylation of the SNCA promoter in

Conclusions

Disorder salient changes that increase the risk of an eating disorder may be present in systems that regulate and/or contribute to weight and energy homeostasis. If these systems function normally, individuals with the same psychological profile may be primarily at risk of other psychiatric problems such as anxiety or obsessive compulsive disorder (OCD). Adaptability in systems regulating energy homeostasis may be diverse in the population and individual differences could contribute to the

Conflict of interest

The authors have no conflicting interests.

Acknowledgements

This work was supported by a UK Department of Health NIHR Programme Grant for Applied Research (RP-PG-0606-1043), by a Multicentre EU Marie Curie Research Training Network grant, INTACT (MRTN-CT-2006-035988) and by a grant from the National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health award to the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King's College London. The views expressed herein are not necessarily

References (208)

  • R.S. Duman et al.

    Epigenetic marking and neuronal plasticity

    Biol. Psychiatry

    (2007)
  • S.J. Duthie

    Folic-acid-mediated inhibition of human colon-cancer cell growth

    Nutrition

    (2001)
  • S.J. Duthie et al.

    Impact of folate deficiency on DNA stability

    J. Nutr.

    (2002)
  • H.M. Ehrenberg et al.

    Low maternal weight, failure to thrive in pregnancy, and adverse pregnancy outcomes

    Am. J. Obstet. Gynecol.

    (2003)
  • S. Ehrlich et al.

    Promoter specific DNA methylation and gene expression of POMC in acutely underweight and recovered patients with anorexia nervosa

    J. Psychiatr. Res.

    (2010)
  • K.A. Fawcett et al.

    The genetics of obesity: FTO leads the way

    Trends Genet.

    (2010)
  • C. Gelegen et al.

    Difference in susceptibility to activity-based anorexia in two inbred strains of mice

    Eur. Neuropsychopharmacol.

    (2007)
  • C. Gelegen et al.

    Chromosomal mapping of excessive physical activity in mice in response to a restricted feeding schedule

    Eur. J. Neuropsychopharmacol.

    (2010)
  • V. Glover et al.

    Association between maternal and amniotic fluid cortisol is moderated by maternal anxiety

    Psychoneuroendocrinology

    (2009)
  • M.E. Gluck

    Stress response and binge eating disorder

    Appetite

    (2006)
  • P.D. Gluckman et al.

    Evolution, development and timing of puberty

    Trends Endocrinol. Metab.

    (2006)
  • J. Hebebrand et al.

    Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia

    Physiol. Behav.

    (2003)
  • S.G. Hofmann

    Enhancing exposure-based therapy from a translational research perspective

    Behav. Res. Ther.

    (2007)
  • G. Jia et al.

    Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO

    FEBS Lett.

    (2008)
  • A.L. Lim et al.

    Genomic imprinting effects in a compromised in utero environment: implications for a healthy pregnancy

    Semin. Cell Dev. Biol.

    (2010)
  • F. Lussana et al.

    Prenatal exposure to the Dutch famine is associated with a preference for fatty foods and a more atherogenic lipid profile

    Am. J. Clin. Nutr.

    (2008)
  • A. Aerni et al.

    Low-dose cortisol for symptoms of post-traumatic stress disorder

    Am. J. Psychiatry

    (2004)
  • C.H. Andreasen et al.

    Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation

    Diabetes

    (2008)
  • J.A. Armitage et al.

    Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals?

    J. Physiol.

    (2004)
  • D.J. Barker

    The developmental origins of adult disease

    J. Am. Coll. Nutr.

    (2004)
  • R.L. Batterham et al.

    PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans

    Nature

    (2007)
  • S.B. Baylin et al.

    Genomic biology: the epigenomic era opens

    Nature

    (2007)
  • O. Berton et al.

    Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress

    Science

    (2006)
  • M.A. Blais et al.

    Pregnancy: outcome and impact on symptomatology in a cohort of eating-disordered women

    Int. J. Eat. Disord.

    (2000)
  • F.H. Bloomfield et al.

    Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring

    Endocrinology

    (2003)
  • M.M. Boggiano et al.

    Binge eating in rats produced by combining dieting with stress

    Curr. Protoc. Neurosci.

    (2006)
  • S.R. Bornstein et al.

    Approaching the shared biology of obesity and depression: the stress axis as the locus of gene-environment interactions

    Mol. Psychiatry

    (2006)
  • A.S. Brown et al.

    Further evidence of relation between prenatal famine and major affective disorder

    Am. J. Psychiatry

    (2000)
  • C.M. Bulik et al.

    The genetics of anorexia nervosa

    Annu. Rev. Nutr.

    (2007)
  • C.M. Bulik et al.

    Patterns of remission, continuation and incidence of broadly defined eating disorders during early pregnancy in the Norwegian Mother and Child Cohort Study (MoBa)

    Psychol. Med.

    (2007)
  • S. Carmichael et al.

    The pattern of maternal weight gain in women with good pregnancy outcomes

    Am. J. Public Health

    (1997)
  • O. Carrera et al.

    Early handling reduces vulnerability of rats to activity-based anorexia

    Dev. Psychobiol.

    (2006)
  • A. Caspi et al.

    Gene-environment interactions in psychiatry: joining forces with neuroscience

    Nat. Rev. Neurosci.

    (2006)
  • A. Chmurzynska

    Fetal programming: link between early nutrition DNA methylation, and complex diseases

    Nutr. Rev.

    (2010)
  • F. Connan et al.

    Poor social comparison and the tendency to submissive behavior in anorexia nervosa

    Int. J. Eat. Disord.

    (2007)
  • R.V. Considine

    Human leptin: an adipocyte hormone with weight-regulatory and endocrine functions

    Semin. Vasc. Med.

    (2005)
  • J. Cornish et al.

    Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo

    J. Endocrinol.

    (2002)
  • K.M. Culbert et al.

    Prenatal hormone exposure and risk for eating disorders: a comparison of opposite-sex and same-sex twins

    Arch. Gen. Psychiatry

    (2008)
  • L. Currin et al.

    Time trends in eating disorder incidence

    Br. J. Psychiatry

    (2005)
  • G. D’Agostino et al.

    alpha-Melanocyte stimulating hormone: production and degradation

    J. Mol. Med.

    (2010)
  • Cited by (87)

    • Eating disorders

      2023, Encyclopedia of Mental Health, Third Edition: Volume 1-3
    • Stress hormones and eating disorders

      2019, Molecular and Cellular Endocrinology
    • Development of loss of control eating

      2018, Pediatric Food Preferences and Eating Behaviors
    • Recent Advances in Consumer Science

      2018, Methods in Consumer Research, Volume 1: New Approaches to Classic Methods
    View all citing articles on Scopus
    View full text