News: Depression: A Failure to Regulate?

Brain imaging study shows differences in circuit that quiets negative emotions

by Nicky Penttila

August 16, 2007

When coping with negative images, people with clinical depression show different—and sometimes opposite—activity in some brain circuits that regulate emotion than people without the illness, according to a new study. And the harder they consciously try to quell their negative emotional responses, the less successful they appear to be.

Scientists at the University of Wisconsin in Madison studied pupil dilation, an automatic response to how hard someone is thinking about and paying attention to a negative stimulus. The researchers were thus able to connect effort with activity in emotional regions of the brain. The study appears in the August 15 issue of the Journal of Neuroscience.

"It's normal for people to have negative emotions in certain circumstances," says lead study author Tom Johnstone. "One of the features of major depression is not that people have negative reactions to negative situations, it's that they can't pull themselves out of those negative emotional moods. They seem to have a deficit in their ability to be able to regulate their emotions ... to come back down to baseline after a negative experience."

Teaching a new trick

First, researchers had the subjects practice strategies to lessen or strengthen their negative response to images they were being shown, such as imagining a photo of a barking dog as meaning that it was happy and wanting to be petted—or that it was angry and about to attack them. The images were designed to provoke strong positive or negative emotional responses.

The participants practiced the strategies until they and researchers were satisfied they understood and could perform the tasks. The study included 21 clinically depressed people and 18 matched controls.

"We ask them to reframe the content of what they're seeing," rather than divert their attention or distract themselves with unrelated thoughts, Johnstone says. "We hope to engage cognitive areas in reinterpreting the emotional content of a stimulus ... to either increase or decrease its impact."

Then, in a functional magnetic resonance imaging scanner, the participants watched a series of negative images, trying to boost or decrease their response or simply pay attention as prompted. Throughout the tasks, researchers measured the relative changes to the diameter of the participants' pupils.

Hard work does not always work

In both healthy and depressed people, the researchers found that responding to the prompts did increase brain activity in prefrontal cortical areas known to help regulate the emotional response centers of the brain. The difference was in the reactions of the emotional centers themselves, including the amygdala and the insula, regions crucial for generating involuntary emotional responses.

In people who were not depressed, more prefrontal (regulatory) activity correlated with lower activity in the emotional response centers—their thoughts successfully quelled their emotional responses. In people with depression, more prefrontal activity did not affect the high levels of activity in emotional response centers, and they remained high.

"Those [healthy] individuals putting more cognitive effort into it are getting a bigger payoff in terms of decreasing activation in these emotional centers," Johnstone says. "In the depressed individuals, you find the exact opposite relationship—it seems the more effort they put in, the more activation there is in the amygdala."

The next step is to discover what causes this difference. It does not appear to be maturity: The (adult) subjects' age did not appear to affect their results. One theory is that depressed people have a broken link between the brain regions so that regulatory centers fail to send any dampening signals to emotional centers. Or depressed people may ruminate, falling into a habit of focusing their thoughts relentlessly on the negative emotional content of images or events.

Also important to discover is how extensive this effect is. The people in the study had only an introduction to cognitive reappraisal, a technique taught by therapists to people who have mood disorders. It may be that a longer course of cognitive-behavioral therapy would lessen the negative response—or that people who show the greatest negative response might never benefit from such therapy.  

Many wait for help

Clinical depression is a state of extreme low mood that has disrupted a person's daily life and social functioning. From 7 percent to 18 percent of all people will experience clinical depression, according to a research review published in the Canadian Journal of Psychiatry. According to the World Health Organization, clinical depression is one of the leading causes of disability and lost productivity in the world.

The results of this study may help identify appropriate treatments for the variety of people with depression, the researchers wrote in their report. Further study of brain circuitry could help many others.

"Emotional regulation underlies many psychiatric disorders, not only depression," Johnstone says. "If we understand where the brain circuits are that are important and how they are involved in regulating emotion, then we can target them with different types of therapies."