Enlarged Amygdala Linked to Anxiety in Young Children

Deborah Brauser

November 21, 2013

Measuring the size and connectivity of the amygdala may accurately predict anxiety levels in young children ― even before they have been diagnosed with a disorder, a new imaging study shows.

Investigators found that the participants, all between the ages of 7 and 9 years, who had larger basolateral amygdalae had significantly higher scores on an anxiety checklist than those who had smaller amygdalae.

In addition, stronger functional connections between the amygdala and other brain regions associated with emotion regulation were significantly linked to high anxiety levels.

"I think the major finding is that we found this enlargement in these children, and we can use that and the hyperconnectivity between the amygdala and other areas to predict levels of anxiety," Shaozheng Qin, PhD, from the Departments of Psychiatry and Behavioral Sciences at Stanford University School of Medicine in California, told Medscape Medical News.

"We were a little surprised because these findings are usually found in adolescent or adult patients with anxiety disorders. But none of our young participants had a clinical diagnosis of any kind," said Dr. Qin.

The investigators add that the results do not say definitively that these kids will go on to develop a mood or anxiety disorder as adults.

"But it is an important step in the identification of young children at risk for clinical anxiety," said senior author Vinod Menon, PhD, also from Stanford, in a release.

The study was published online November 20 in Biological Psychiatry

Early Changes

The investigators enrolled 76 typically developing children (50% boys) between the ages of 7 and 9 years.

"For the cognitive emotional assessments to be reliable, 7 years old is about as young as a child can be. But the changes to the amygdala may have started earlier," explained Dr. Menon.

The Childhood Behavior Checklist (CBCL) was filled out by the participants' parents. None of the children were using any medication or were considered to be clinically anxious.

Dr. Shaozheng Qin

Magnetic resonance imaging (MRI) was used to measure the size of various subregions of the amygdala in each child, and functional MRI (fMRI) was used to measure connectivity.

Results showed that children with high anxiety scores on the CBCL had significantly larger amygdala volume compared with those with lower scores (P < .001). However, additional "machine learning algorithm" analysis showed that only enlarged left, and not right, amygdala volume predicted childhood anxiety (P < .005).

When examining specific subregions of the amygdala, the investigators found that enlargements in the left basolateral area had the strongest association with high anxiety scores (P < .001), followed by the left superficial amygdala (P < .01).

The children with higher anxiety scores also had stronger functional connections, as shown on the fMRI scans, between the left basolateral amygdala and multiple areas of the brains. These included

  • the sensory-perceptual association system,

  • the dorsal fronto-parietal attentional network,

  • the ventral striatum reward and motivational system, and

  • the anterior insula and ventromedial prefrontal cortex.

"All 4 of these core systems are impacted by childhood anxiety," said Dr. Qin.

Origins of Anxiety

"Critically, machine learning algorithms revealed that levels of childhood anxiety could be reliably predicted by amygdala morphometry and intrinsic functional connectivity," write the researchers.

The investigators noted that they were surprised by how significant the alterations to the amygdala's structure and connectivity were in those with high anxiety scores, especially because of the children's young ages and because their baseline anxiety levels were not considered to be clinical.

"The study provides important new insights into the developmental origins of anxiety," added Dr. Menon.

However, Dr. Qin noted that more research is needed before any clinical recommendations can be made, and that they are not recommending that all children undergo expensive imaging. Instead, their study illustrates that children with high anxiety, even if the anxiety is below clinical levels, should be watched for possible future problems.

He reported that the investigators are continuing to follow many of these children and are making plans to start enrolling participants for a bigger longitudinal study soon.

The study was funded by grants from the National Institutes of Health, the Natural Science Foundation of China, the Netherlands Organization for Scientific Research, the National Science Foundation, Stanford Clinical and Translational Science Award, the Child Health Research Institute at Stanford University, and the Lucile Packard Foundation for Children's Health. The study authors have disclosed no relevant financial relationships.

Biol Psychiatry. Published online November 20, 2013.

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