Early Stress Linked to Weaker Brain Connections, Anxiety

Pam Harrison

November 14, 2012

Exposure to a stressful home environment in infancy leads to higher cortisol levels in preschool-aged girls, and in adolescence, weaker connections between areas of the brain involved in emotional regulation, new research shows.

Weaker connectivity between these areas of the brain in turn predicts symptoms of anxiety during adolescence in girls but not in boys.

"What we are showing is a link with resting-stage brain activity, which we think is representative of how well different brain areas are communicating with each other," Cory Burghy, PhD, University of Wisconsin–Madison, told Medscape Medical News.

"And we were able to establish this predictive pathway of association where young girls in stressful homes in the first year of life were showing high afternoon cortisol levels, and these cortisol levels predicted lower brain connectivity between the amygdala and the prefrontal cortex in adolescence, and this in turn predicted higher levels of anxiety in girls."

The study was published online November 11 in Nature Neuroscience.

Imaging Findings

"We wanted to understand how stress early in life impacts patterns of brain development which might lead to anxiety and depression," Dr. Burghy said in a press release.

For the study, the investigators used a method called resting-state functional connectivity magnetic resonance imaging (fcMRI) to map the strength of connections between the amygdala and the prefrontal cortex in 57 adolescents — 28 females and 29 males.

They then looked back at earlier results and found that those girls with weaker connections between these 2 areas of the brain had lived as infants in homes where their mothers had reported higher general stress levels.

Near the time of the scan, researchers asked the adolescents about symptoms of anxiety as well as stress levels in their current lives.

Current levels of anxiety were not related to patterns of brain connectivity.

However, researchers did observe that greater levels of early lifetime stress led to higher afternoon cortisol levels in girls, a sign that the child is not dealing well with day-to-day stressors, said Dr. Burghy.

At the age of 18 years, investigators were able to demonstrate that girls exposed to early lifetime stress had weaker connections between the amygdala, the threat center, and the prefrontal cortex, which is involved in emotional regulation.

This association explained about 65% of the variance observed in teenage anxiety levels.

"These measures of brain function are actually accounting for a substantial proportion of what is explainable in anxious symptoms," said study coinvestigator Richard Davison, PhD.

"So this underscores the relevance of this brain circuitry because the stronger the association, the more likely this circuit underlies these kinds of symptoms," he added.

Subtle Sex Differences

Bruce S. McEwen, PhD, Rockefeller University, New York City, told Medscape Medical News that the fact that females are affected fits in with the growing view that there are subtle sex differences in neural architecture and function that involve many, if not all, brain regions.

"Sex hormones act during development and also in adult life via a variety of mechanisms in virtually all brain regions, and their effects interact with those of experiences, which also change brain architecture and function," said Dr. McEwen, who was not involved in the research.

As a result, he added, men and women do many of the same things equally well, but they differ in the strategies they use.

In the case of adverse outcomes, "women tend to express more depression and anxiety disorders," he said.

Men, on the other hand, turn to more substance abuse and antisocial behavior —"which I think is an illustration of this concept," Dr. McEwen added.

The study was funded by the National Institute of Mental Health and the John D. and Catherine T. MacArthur Foundation Research Network on Psychopathology and Development. The authors have disclosed no relevant financial relationships.

Nat Neurosci. Published online November 11, 2012. Abstract