It is widely recognized that stress can trigger eating disorders such as binge eating, which is more common in females than in males. It was once thought that the link was purely psychological, but researchers are increasingly turning to genetics and biology for explanations. Now, a new study of mice shows that stress during late pregnancy rewires the brain and predisposes female offspring to demonstrate binge-like behavior. The study also suggests that binge eating may be prevented by changing the balance of certain nutrients in adolescence.
The study - by researchers from the Weizmann Institute of Science in Israel and the Max Planck Institute of Psychiatry in Munich, Germany - is published in the journal Cell Metabolism.
Binge eating disorder is a condition in which a person loses control of their eating habits and has recurring episodes of consuming large amounts of food in a short time, even when they are full or not hungry.
People affected by binge eating disorder are often overweight or obese, and they can also experience shame, guilt, or distress about the condition, which can lead to more episodes of binge eating.
Binge eating is the most common eating disorder in the United States, where around 2.8 percent of people are likely to be affected by the condition at some point in their lives.
As with other eating disorders, binge eating usually starts during adolescence or early adulthood. While it can affect both sexes, it is 2.5 times more common in women than in men.
Research is increasingly revealing that eating disorders such as binge eating arise from complex patterns of genetic, biological, psychological, and social factors.
For example, scientists who are trying to understand why certain eating disorders run in families are looking at gene variants that might raise the risk of developing the conditions.
Other teams are showing, through imaging studies, that patterns of brain activity in women with eating disorders are different to patterns in women without the disorders.
Prenatal stress affects female offspring differently
In girls, the symptoms of binge eating disorder often start during puberty. Previously, scientists had looked to psychology to explain the causes, but more recently, they have also turned their attention to biology.
They also note that it is widely recognized that stress at or near birth affects the fetus and can predispose offspring to "various psychiatric and metabolic disorders," and this can affect males differently to females.
So, for their investigation, they used specially bred mice to examine the link between prenatal stress and binge eating behavior in female offspring.
Joint senior author Prof. Alon Chen, who heads groups researching the neurobiology of stress at both the Weizmann and Max Planck Institutes, says that they "established a model where [they] can actually show that early life stress increases the likelihood of binge eating in females."
Using the mouse model, they also made the second important finding of the study: that stress before birth alters the brain circuits of female offspring.
The brain changes are epigenetic in nature, meaning that they do not alter the code of the genes, but they tag them with chemical markers that alter the behavior of the genes.
Team manipulated one particular stress circuit
The team engineered the mice so that they could manipulate the brain circuit that releases stress hormones such as cortisol.
Although stress is associated with several brain processes, the team wanted to focus on one in particular: the one that involves corticotropin-releasing factor (CRF), which in humans is linked to inflammation, suppressed appetite, and anxiety.
In order to ensure that only the CRF stress circuit became active, the team developed a way to trigger it genetically without having to handle the mice; it is known that handling by humans activates many stress circuits in the animals.
The researchers introduced the trigger in the third trimester of the engineered pregnant mice by changing their water.
When the team examined the hypothalamus tissue of the stressed females' offspring, they found that it contained epigenetic markers in the form of methyl tags.
However, it was only when those pups were then placed under stress - by restricting their access to food - that they started to show binge eating behavior.
The mice were given a 2-hour window only three times per week during which they could eat as much as they wanted. They ate excessive amounts of food extremely fast during these periods.
The group of control female mice that were bred and raised in the same way, but who were not put on a restricted access regimen, did not show binge eating behavior.
Altering methyl-rich foods prevented binge eating
In their discussion, the authors draw comparisons with human situations in which there is a "wide availability of food rich in fat and carbohydrates combined with the frequent self-imposed diet constraint by adolescent girls (turning palatable food into 'forbidden')."
In other words, could it be that girls who are epigenetically predisposed to binge eating be triggering the condition through the stress of a self-imposed diet?
Epigenetic markers are placed onto genes by cells, which, in the case of methyl markers, grab the methyl from methyl-rich nutrients such as vitamin B and folate, which come from the digestion of food.
In a final set of tests, the researchers showed that it was possible to prevent binge eating behavior in susceptible adolescent female mice by feeding them a diet with a different balance of foods that are rich in methyl.
However, the team also points out that because they found the methyl-balanced diet worked in mice, it does not mean that the same would be true of humans. "We found a balance, but it might not be the relevant balance for humans. This is something that needs to be tested," Prof. Chen explains.
Nevertheless, the team believes that the findings will improve our understanding of the role of the brain in eating disorders, as well as emphasize how important it is that women should avoid stressful situations as much as they can when they are pregnant, as Prof. Chen concludes:
"We all know this, but people ignore it for various social or economic reasons. But the price we pay later in life - whether it's psychiatric disorders, metabolic syndromes, or heart-related illnesses - is heavily impacted by the way [our] brain was programmed early in life."