New neuroimaging research published in JAMA Psychiatry helps to untangle the links between irritability, anxiety, and brain functioning in youths. The findings suggest that irritability and anxiety have interactive, rather than additive, effects when processing negative social information.

I am a practicing child and adolescent psychiatrist. Over the years, I have met with families struggling with all types of anxiety and irritability, explained study author Joel Stoddard of the University of Colorado and Childrens Hospital Colorado.

When I was early in my career, I began to appreciate that even though anxiety and irritability seem like straightforward symptoms, their presentation is often intermingled. We simply dont know why they co-occur or conversely why a child might have one symptom but not the other.

Moreover, there was very little work looking at both symptoms together, especially without a focus on traditional mental health diagnoses. At the time this study started, mental health research was moving away from traditional diagnoses because most arent well grounded in biology. Though the transition has been difficult, it also gave clinical scientists room to restart simply, said Stoddard, who also leads the Emotion and Development Lab.

In this study we examined symptoms in a group of children diagnosed with clinically significant affective issues. Are these symptoms related to how the basic emotion recognition circuitry responds to facial expressions?

The researchers used functional magnetic resonance imaging to examine the brain activity of 115 youths aged 8 to 17 years as they completed a face emotion processing task. About 90 of the participants had been diagnosed with anxiety, disruptive mood dysregulation, and/or attention-deficit/hyperactivity disorders. The youths and their parents also completed assessments of the participants irritability and anxiety.

Stoddard and his colleagues found that high levels of both anxiety and irritability were associated with decreased connectivity between the amygdala and medial prefrontal cortex when viewing angry facial expressions. High levels of anxiety but low levels of irritability, on the other hand, were associated with increased connectivity in this brain circuit. The amygdala is known to be important for responses to threatening situations, while the medial prefrontal cortex is associated with decision-making processes.

This is a demonstration that the response of amygdala-centered brain networks to emotional expressions differs by anxiety and irritability in children who we might very well see in the clinic, Stoddard told PsyPost.

Had we looked at either symptom alone, we might have missed how they respond differently. For example, we observed that changes in the prefrontal-amygdala network during viewing angry faces differ by an individuals degree of anxiety or irritability. These differences offer important clues about the neural function youth who may express anxiety, irritability, or both. But these are clues, I dont think much more should be taken from this study by itself.

Increased irritability by itself, meanwhile, was associated with increased activity in several brain regions in response to angry faces and happy faces compared to fearful faces.

But as with all research, the study includes some limitations.

This study used functional magnetic imaging in children with serious emotional issues, these facts are the source of strengths and weaknesses. Clearly major strengths are that we examined the clinical population directly and used a noninvasive, largely safe method of measuring localized brain activity. However, it is very difficult to get a good brain signal from youngsters because they move, causing a blurry image (especially for network imaging), or get tired of the task (so their brain responses may change), Stoddard explained.

Also, we could not ethically ask the participants to stop their medications or pause therapy risking harm. Also, if we did so, we might be studying the effects of discontinuation. On the other hand, if we only invited kids who didnt need treatment, we might not study a group of youth who represent the conditions we see in clinics. We also didnt focus on anxiety and irritability in some conditions like bipolar disorder or active posttraumatic stress or in different cultural contexts. Though there are caveats with each aspect of the study, it represents an interesting result and considerable effort by participants and experts.

This type of work is critical to build a strong foundation for understanding the brain mechanisms. It is part of a growing body of literature that is revealing how brain networks function differently by development, experience, or clinical symptoms. I personally find this emerging literature satisfying, because I see complicated clinical pictures. Some stories are simpler, such as dysfunction in a single gene or brain region. These occasionally explain a lot for rare conditions, but rarely much for common conditions, Stoddard added.

This work was a team effort. I contributed to it as part of my research training fellowship at the National Institutes of Mental Health and as an assistant professor at the University of Colorado, School of Medicine, Department of Psychiatry, Division of Child and Adolescent Psychiatry. I continue to have that latter title and am an outpatient psychiatrist at the Childrens Hospital Colorado. Im supported by all those organizations to study pediatric anxiety and irritability. The content is solely my responsibility and does not necessarily represent the official views of the National Institutes of Health, the University of Colorado, or Childrens Hospital Colorado.

The study, Association of Irritability and Anxiety With the Neural Mechanisms of Implicit Face Emotion Processing in Youths With Psychopathology, was authored by Joel Stoddard, Wan-Ling Tseng, Pilyoung Kim, Gang Chen, Jennifer Yi, Laura Donahue, Melissa A. Brotman, Kenneth E. Towbin, Daniel S. Pine, and Ellen Leibenluft.

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Study provides new insight into the neural circuitry underlying irritability and anxiety in youths - PsyPost