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Epigenetics offers a glimmer of hope for future anorexia treatment

Anorexia affects about 2% of women in their lifetime, although one in every ten sufferers is male. Darwin Bell

Most people know that anorexia nervosa is a psychiatric illness associated with the maintenance of low weight and fear of weight gain. But we know very little about what causes this destructive disease, which is associated with the highest mortality rates of any psychiatric illness.

Anorexia affects about 2% of women in their lifetime, although one in every ten sufferers is male. Between the ages of 15 and 24, suffering from anorexia nervosa means you’re 12 times more likely to die. It’s clearly a serious illness, but there are many myths about what causes it.

Causes

Twin studies, which compare identical with non-identical twins, tell us that both genes and the environment cause anorexia nervosa. In other words, nurture and nature both play a role.

Unhelpful types of environments include pressure to be thin, experiencing criticism about appearance, and teasing or negative comments about weight from family or peers.

Our cultural environment places pressure to be thin on all of us. Research from the Czech Republic shows that the prevalence of anorexia nervosa in the country increased after the Berlin Wall came down and western-style advertising – with its focus on thin bodies and the thin ideal – became much more pervasive.

But this environmental factor fails to explain why anorexia nervosa is relatively rare in the face of ubiquitous exposure to the thin ideal. After almost two decades of twin research in the area of eating disorders, there’s now general agreement that anorexia nervosa is substantially influenced by genes. Indeed, genes are thought to account for around 60% of the cause of this eating disorder.

To date, research has not be able to isolate the specific genes that have most influence in causing anorexia nervosa, but work involving other psychiatric disorders suggests that there will be many rather than a few genes at play. Research trying to identify the genes that have a role in anorexia nervosa is currently underway across the world.

Epigenetics

A recent story in National Geographic about twins discussed the “third factor” at play in causing disorders such as anorexia nervosa, in addition to nature and nurture.

This third factor is called epigenetics and has the potential to revolutionise our understanding of anorexia’s causality. Epigenetics is a mechanism by which the environment directly impacts genes via a process called DNA methylation, which can make the expression of genes weaker or stronger, or indeed turn genes on or off.

The most famous example of epigenetics comes from the work of two researchers who compared two types of mother rats – those that patiently licked their offspring after birth and those that neglected their newborns.

The licked newborns grew up to be relatively brave and calm while the neglected newborns were much more anxious. After analysing the brain tissue of both licked and unlicked rats, the researchers found distinct differences in the DNA methylation patterns in the hippocampus (the elongated ridges on the floor of both sides of the brain, thought to be the centre of emotion, memory, and the autonomic nervous system) cells of each group.

Remarkably, the mother’s licking activity had the effect of removing dimmer switches on the gene that shapes stress receptors in the pup’s growing brain. Compared to the neglected pups, the well-licked rats had better developed hippocampi and released less of the stress hormone cortisol, making them calmer when startled.

Importantly, the researchers were able to reverse the epigenetic signals by injecting a drug (trichostatin A) into the brains of adult rats. In effect, they were able to simulate the effect of good (and bad) parenting with a pharmaceutical intervention. Trichostatin, interestingly, is chemically similar to the drug valproate, which is used clinically as a mood stabiliser.

Epigenetics and anorexia nervosa

The study of the role of epigenetics in anorexia nervosa is still in its very early days. Recent studies have shown both general and gene-specific alterations in DNA methylation in the blood of people with anorexia nervosa. This suggests that malnourishment may switch off or turn down certain genes which, if switched back on, may help those with anorexia nervosa regain weight.

Other possible epigenetic switches are unknown but we can speculate that, given a recent study found significantly more births of people with anorexia nervosa in spring and summer compared to other seasons, that vitamin D levels during pregnancy may also play a role.

Epigenetics is an area that holds great promise for the development of interventions that can address the epigenetic changes and “switch” helpful genetic action on.

Anorexia nervosa is likely to be caused by a complex interaction of multiple influences, and epigenetics has the potential to help us start to better understand this complexity.

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