Concurrent Psychiatric Symptoms Impact Brain Function in Pediatric Patients


Irritability was associated with widespread neural activation or increased activity in the insula, caudate, dorsolateral and ventrolateral prefrontal cortex, and inferior parietal lobule.

Katherina Kircanski, PhD

Katherina Kircanski, PhD

Pediatric psychiatric patients often present with synchronous symptoms, but research generally focuses on 1 symptom or diagnosis in isolation. Researchers from a new study have found a way to study multiple symptoms at the time and tease how each can affect brain function.

“Using brain imaging and new statistical approaches, we were able to examine 2 common types of symptoms simultaneously—irritability and anxiety — and separate out their unique and shared associations with brain functioning,” study author, Katherina Kircanski, PhD, Research Fellow in the Intramural Research Program at the National Institute of Mental Health (NIMH), Emotion and Development Branch told MD Magazine.

Researchers ultimately found that irritability was associated with more widespread dysfunction throughout the brain than was anxiety.

Neuroimaging data was compiled from 197 participants aged 8-18 years, from June 30, 2012 to June 28, 2016. Of the 197, there were 56 with no psychiatric diagnosis, 54 with disruptive mood dysregulation disorder (DMDD), 50 with anxiety disorder, and 37 with attention-deficit/hyperactivity disorder (ADHD). The participants’ mean age was 13.1, with 58% being male.

Parents and participants rated irritability levels by using the Affective Reactivity Index (ARI), and anxiety levels by using the Screen for Child Anxiety Related Emotional Disorders (SCARED). For the statistical analysis, researchers used the bifactor model to quantify the distinct and shared differences of irritability and anxiety symptoms. An MRI dot probe task assessed attention orienting to angry versus neutral faces.

Results show that irritability was associated with widespread neural activation or increased activity in the insula, caudate, dorsolateral and ventrolateral prefrontal cortex, and inferior parietal lobule (P < .001 for all). Higher anxiety was associated with decreased amygdala connectivity to the cingulate, thalamus, and precentral gyrus.

Kircanski said that mental health professionals have been attempting to focus more on personalized medicine, finding out what treatments work best for which patients.

“Some treatments for irritability versus anxiety might be quite different in that they would target the different patterns of brain dysfunction that we showed here,” Kircanski said. “For instance, treatments for irritability might need to target more widespread brain circuitry, or non-invasive brain stimulation interventions that target brain regions specific to each symptom.”

Through this method, the study result provide means for deeper analysis and aids researchers in developing novel treatments. Researchers implored follow-up studies to replicate these findings in another group of participants, which would lend to stronger support for the evidence and potential treatment implications.

“It’s also important to test this statistical approach across other types of patient samples and brain imaging tasks,” Kircanski said. “Because co-occurrence is ubiquitous in both child and adult psychiatry, it’s important to develop and utilize methods to study multiple types of symptoms simultaneously, parallel to how patients present in the community.”

The study, "A Latent Variable Approach to Differentiating Neural Mechanisms of Irritability and Anxiety in Youth," was published online in JAMA Psychiatry this month.

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