Standing up to stress, for the body and mind

An illness can cause damage well beyond any traditional notion of where the boundaries of its wounds might lie. A case in point is hypertension – high blood pressure – which has been shown to have a very close association with depression.

A strong link might seem counterintuitive. The two disorders have long been categorized separately: one physical, one mental. Hypertension is diagnosed from physical measurements of blood pressure, clinical depression from the words of a patient.

But mind and body are part of one creature, and the research is unequivocal. Someone with hypertension is more likely to develop depression down the road, and depression increases the risk of high blood pressure.

The results are broader still: There’s an association between a range of psychiatric disorders and all kinds of cardiovascular disease, from hypertension to clogged arteries to heart failure.

Susan Wood, an assistant professor in the School of Medicine, is helping map the connections between ailments of the mind and body. Although she works with laboratory rats, her research is rooted in well-established clinical results.

“In humans, if we passively cope with stress – if we just kind of let it happen – it’s associated with an increased risk of developing psychiatric disorders,” she says. “But if we proactively cope and take a stand, saying, ‘I’m not going to let this affect me,’ then it’s associated with being resilient to the stress.”

Wood uses an animal model involving a small rat confronted by a much larger one. Hierarchical by nature, a rat feels stress when facing a much-larger rat, and some have a submissive reaction – they roll onto their backs.

“This is a response they adopt naturally,” Wood says. “And in seven years of studying this model, I’ve found that this submissive, passive response leads to pathology.” That includes depressive-like symptoms and biomarkers indicating that cardiovascular disease is soon to follow.

Some don’t roll over, though. They stand up for themselves and rarely lie on their backs.

In the face of stress, they’re resilient to many of the consequences associated with the passive response. They develop neither depressive-like symptoms nor the markings of impending cardiovascular disease.

“I think that’s one of the great features of this model,” Wood says. “It mimics what we see in humans. If you passively cope, you’re more vulnerable. In this animal model, if you passively cope, you’re more vulnerable as well. It increases the translational value of the research.”

Signs of inflammation are an important part of the research.

“Inflammation is a big topic right now,” she says. “It’s known to be associated with so many different disorders – with arthritis, with depression, with cardiovascular disease, with diabetes.

“Recently, we’ve started to understand that not only is the inflammation that’s going on in our bodies – south of the blood-brain barrier, basically – contributing to these diseases, but that stress can produce changes in the inflammatory factors in the brain as well.”

Using her animal model, Wood has shown a distinct difference between the brains of passive and active coping individuals: Some markers for inflammation are increased in the former but suppressed in the latter.

“I’ve spent years identifying brain regions, neuromodulators and neurochemical changes that are associated with these two very different responses,” says Wood. “So now we’re going to see if we can actually produce the response. Instead of just saying there’s an association, we are working towards making a certain change in the brain to promote stress resilience.

“That’s going to open up novel treatment options for these co-occurring disorders and therapeutics with the potential to produce a more resilient individual in the face of stress.”

Watch the video

Watch a video with Susan Wood about her research. This article was adapted from the Winter 2014 issue of Breakthrough, the university’s research magazine. Wood's work has been supported by a NARSAD Young Investigator Award and an American Heart Association Award.

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