Early life exposure to bisphenol A (BPA) heightens anxiety by altering gene expression in the amygdala, a region of the brain that plays a role in shaping responses to fear and stress. But a diet rich in soy can lessen this effect.

These are the findings of an animal study led by researchers at North Carolina State University who write about their findings in a paper published online in the open access journal PLoS ONE on 5 September.

BPA is an organic industrial chemical that is controversial because it has hormone-like properties similar to those of estrogen. BPA is used to make a range of polycarbonate plastics and epoxy resins, and has been present in many hard plastic bottles and metal-based food and beverage cans since the 1960s.

Lead author Heather Patisaul, an associate professor of biology at NC State, told the media:

“We knew that BPA could cause anxiety in a variety of species, and wanted to begin to understand why and how that happens.”

For their study, Patisaul and colleagues raised five groups of rats from gestation through puberty. Two were exposed to to low doses of BPA via drinking water (1 mg/L): one was fed a soy-based diet, the other a soy-free diet.

Two other groups of rats, one fed on soy-free, the other on a soy-rich diet, were not exposed to BPA, plus the fifth group was exposed to estrogen (ethinyl estradiol), and a soy-free diet.

Tests showed that the rats exposed to BPA had blood levels within the range found in humans. They also showed that those fed a soy diet had levels of genistein, an estrogen-like compound present in soy, within the range found in humans who follow a vegetarian diet and eat soy foods on a regular basis.

The results showed that both male and female BPA-exposed adolescent rats raised on the soy-free diet had significantly higher levels of anxiety.

And, for the first time, the researchers found the raised anxiety was linked to changes in gene expression in the brain.

The gene expression changes were in a region of the brain that is known to play a part in influencing responses to fear and stress: the amygdala.

The affected genes included the estrogen receptor beta and the melanocortin receptor 4, both of which are involved in the release of oxytocin, a hormone and neurotransmitter that has been linked to social behavior:

“These data also reveal that, because [estrogen receptors] and melanocortin receptors are crucial to their function, oxytocin/vasopressin signaling pathways, which have previously been linked to human affective disorders, may underlie these behavioral outcomes,” write the authors.

However, the researchers did not find higher levels of anxiety in the male and female BPA-exposed adolescent rats that were raised on the soy-rich diet.

Perhaps compounds present in soy lessen the hormone-disrupting effect of BPA, speculate the researchers. But this also raises questions about soy itself, as Patisaul explains:

“Soy contains phytoestrogens that can also affect the endocrine system, which regulates hormones.”

“It is not clear whether these phytoestrogens are what mitigate the effect of BPA, or if it is something else entirely,” she adds.

The team now wants to look further into that question.

Grants from the National Institute of Environmental Health Sciences (NIEHS) and National Institutes on Aging helped pay for the study.

Written by Catharine Paddock PhD