U.S.A. Anxiety disorders affect up to 18% of Americans and 14% of Europeans. Unfortunately, they are little understood, both by those unaffected and by scientists who continue to try to figure out what causes them.

Dr. Shaozheng Qin is a postdoctoral research fellow at the University of Stanford School of Medicine and the first author of a recent paper that describes a link between increased anxiety in childhood and the structure and connectivity of the amygdala. By looking for specific bio-makers, -physical biological characteristics that can be tied to behavior,- we will eventually be to intervene early on when a child displays high anxiety traits. Here, Dr. Qin discusses what he and his research team found, the implications for childhood anxiety, and the next steps the research community should take in this field.

In your study, you found there is a link between increased anxiety in childhood and the structure and connectivity within the amygdala. To begin, what exactly is the amygdala and why is it important when studying certain emotions like anxiety?

Dr. Shaozheng Qin: The amygdala compasses a group of nuclei located deep and medially the medial temporal lobes of the brain. The amygdala nuclei are known to play a central role in the modulation of cognitive and affective functions through their abundant connections with cortical and subcortical regions.  In other words, the amygdala has been posited as the core of the brain’s emotion circuitry.

We focused on the effects of childhood anxiety on the amygdala structure and connectivity because of two major factors. First, early childhood anxiety have been linked to an increased risk for developing mood and anxiety disorders. Second, research in animals has shown that stressful and anxious experiences during early childhood can induce long-lasting changes in brain structure and function. In particular, early life stress and anxiety have been linked to enlarged amygdala, particularly the basolateral nuclei in animals. Findings from adult and pediatric anxiety are mixed. Thus, we sought to examine the relationship between anxiety and the amygdala structure and connectivity during early childhood – a period when anxiety-related traits begin to be reliably identifiable.

In the results, you found a link between an enlarged amygdala volume and anxiety. How did you make this discovery?

We first obtained each child’s high-resolution (1.5-mm isotropic voxels) 3D anatomical brain images obtained by using magnetic resonance imaging (so-called MRI) technique. We then used an optimized voxel-based morphometry approach to qualify voxel-wise gray matter volume across the whole brain. An initial whole-brain exploratory correlation analysis revealed very strong correlation between gray matter volume of the amygdala and levels of anxiety in children. We further used a cytoarchitectonic mapping of amygdala nuclei to reveal that this enlargement is localized specifically to the basolateral amygdala. Prediction analysis based on machine learning algorithms confirmed that levels of childhood anxiety could be reliably predicted by amygdala morphometry and intrinsic functional connectivity, with the left basolateral amygdala emerging as the strongest predictor.

Why did you specifically only choose children between 7-9 years old?

It is a good question. We focused on children as young as ages of 7 to 9, particularly because it is a period of when anxiety-related traits begin to be reliably identifiable. Especially, each child’s anxiety level in our study was obtained via parental reports on child’s daily life experiences, using the child behavior checklist syndrome scales and the Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented anxiety problems scale.

Why is it important to understand how anxiety begins in children?

Understanding such brain-anxiety association is particularly important not only to advance our knowledge about the neurodevelopmental origins of individual differences in early anxiety, but also to develop predictive biomarkers to identify at-risk children for early intervention.

Does this discovery have any relation to better understanding anxiety disorders?

It should be noted that we focused on typically developing children whose anxiety levels are within a nonclinical range. Thus, our findings cannot be simply translated into clinical population, and it is still far from using for any clinical diagnostics. But, as mentioned above our findings do have potentials for the development of predictive biomarkers to identify at-risk children for early intervention.

What further questions has your study raised?

Our findings suggest that a possible diathesis of anxiety may be alterations in the amygdala structure and connectivity leading to the emergence of trait-like susceptibility to anxiety. On the one hand, interactions between such a diathesis and stress exposure in the developing brain may lead to negative consequences such as anxiety-related disorders. On the other hand, these changes may confer some adaptive advantages for developing balanced strategies to cope with challenging and stressful situations in real life.

What further studies need to be conducted to answer these questions?

Future longitudinal studies are required to address the long-term effects of childhood anxiety on brain development, especially during highly vulnerable periods of childhood and adolescence. Our present study represents an important first step in characterizing altered brain systems and identifying predictive biomarkers of individual differences in childhood anxiety at a young age.


Dr. Qin received his Ph.D. in cognitive neuroscience from Donders Institute for Brain, Cognition and Behaviour in the Netherlands in November of 2010. He currently works as a research fellow at Stanford University School of Medicine. His primary research interest is working to understand the neurological basis of cognitive and affective development in humans, particularly looking at the effects of stress and anxiety on the brain development and in general, learning and memory. The overarching inspiration is to develop intervention programs for preventing affective problems in early development in children.