ReviewEating disorders, gene–environment interactions and epigenetics
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)
- et al.
Gene-environment interactions and obesity—further aspects of genome-wide association studies
Nutrition
(2009) - et al.
Sucrose sham feeding on a binge schedule releases accumbens dopamine repeatedly and eliminates the acetylcholine satiety response
Neuroscience
(2006) - et al.
Enhancing exposure therapy for anxiety disorders with glucocorticoids: from basic mechanisms of emotional learning to clinical applications
J. Anxiety Disord.
(2010) - et al.
Differential epigenomic and transcriptomic responses in subcutaneous adipose tissue between low and high responders to caloric restriction
Am. J. Clin. Nutr.
(2010) - et al.
Leptin in reproduction
Trends Endocrinol. Metab.
(2001) Epigenetic mechanisms and the transgenerational effects of maternal care
Front. Neuroendocrinol.
(2008)- et al.
A neurodevelopmental model for anorexia nervosa
Physiol. Behav.
(2003) - et al.
An investigation of hypothalamic-pituitary-adrenal axis hyperactivity in anorexia nervosa: the role of CRH and AVP
J. Psychiatr. Res.
(2007) - et al.
Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring
J. Nutr.
(2002) - et al.
The eating disorders as addiction: a psychobiological perspective
Addict. Behav.
(1998)
Epigenetic marking and neuronal plasticity
Biol. Psychiatry
Folic-acid-mediated inhibition of human colon-cancer cell growth
Nutrition
Impact of folate deficiency on DNA stability
J. Nutr.
Low maternal weight, failure to thrive in pregnancy, and adverse pregnancy outcomes
Am. J. Obstet. Gynecol.
Promoter specific DNA methylation and gene expression of POMC in acutely underweight and recovered patients with anorexia nervosa
J. Psychiatr. Res.
The genetics of obesity: FTO leads the way
Trends Genet.
Difference in susceptibility to activity-based anorexia in two inbred strains of mice
Eur. Neuropsychopharmacol.
Chromosomal mapping of excessive physical activity in mice in response to a restricted feeding schedule
Eur. J. Neuropsychopharmacol.
Association between maternal and amniotic fluid cortisol is moderated by maternal anxiety
Psychoneuroendocrinology
Stress response and binge eating disorder
Appetite
Evolution, development and timing of puberty
Trends Endocrinol. Metab.
Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia
Physiol. Behav.
Enhancing exposure-based therapy from a translational research perspective
Behav. Res. Ther.
Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO
FEBS Lett.
Genomic imprinting effects in a compromised in utero environment: implications for a healthy pregnancy
Semin. Cell Dev. Biol.
Prenatal exposure to the Dutch famine is associated with a preference for fatty foods and a more atherogenic lipid profile
Am. J. Clin. Nutr.
Low-dose cortisol for symptoms of post-traumatic stress disorder
Am. J. Psychiatry
Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation
Diabetes
Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals?
J. Physiol.
The developmental origins of adult disease
J. Am. Coll. Nutr.
PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans
Nature
Genomic biology: the epigenomic era opens
Nature
Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress
Science
Pregnancy: outcome and impact on symptomatology in a cohort of eating-disordered women
Int. J. Eat. Disord.
Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring
Endocrinology
Binge eating in rats produced by combining dieting with stress
Curr. Protoc. Neurosci.
Approaching the shared biology of obesity and depression: the stress axis as the locus of gene-environment interactions
Mol. Psychiatry
Further evidence of relation between prenatal famine and major affective disorder
Am. J. Psychiatry
The genetics of anorexia nervosa
Annu. Rev. Nutr.
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.
The pattern of maternal weight gain in women with good pregnancy outcomes
Am. J. Public Health
Early handling reduces vulnerability of rats to activity-based anorexia
Dev. Psychobiol.
Gene-environment interactions in psychiatry: joining forces with neuroscience
Nat. Rev. Neurosci.
Fetal programming: link between early nutrition DNA methylation, and complex diseases
Nutr. Rev.
Poor social comparison and the tendency to submissive behavior in anorexia nervosa
Int. J. Eat. Disord.
Human leptin: an adipocyte hormone with weight-regulatory and endocrine functions
Semin. Vasc. Med.
Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo
J. Endocrinol.
Prenatal hormone exposure and risk for eating disorders: a comparison of opposite-sex and same-sex twins
Arch. Gen. Psychiatry
Time trends in eating disorder incidence
Br. J. Psychiatry
alpha-Melanocyte stimulating hormone: production and degradation
J. Mol. Med.
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