NIH researchers found widespread differences in the brains of children with anxiety disorders that improved after treatment
• Press release
Researchers at the National Institutes of Health have found hyperactivation in many brain regions, including the frontal and parietal lobes and the amygdala, in unmedicated children with Anxiety Disorders. They also showed that treatment with cognitive behavioral therapy (CBT) led to improvements in clinical symptoms and brain function. The findings illuminate the brain mechanisms underlying the acute effects of CBT for the treatment of one of the most common mental disorders. The study, published in American Journal of Psychiatryled by NIH National Institute of Mental Health (NIMH) researchers.
“We know CBT is effective. These findings help us understand how CBT works, a critical first step in improving clinical outcomes,” said senior author Melissa Brotman, Ph.D., Chief of the Neuroscience and Neotherapeutics Unit at the NIMH Intramural Research Program.
Sixty-nine unmedicated children diagnosed with an anxiety disorder underwent 12 weeks of CBT according to an established protocol. CBT, which involves changing dysfunctional thoughts and behaviors through gradual exposure to anxiety-provoking stimuli, is the current gold standard for treating anxiety disorders in children.
The researchers used clinician-rated measures to examine change in children’s anxiety symptoms and clinical functioning from pre- to post-treatment. They also used task-based fMRI to examine whole-brain changes before and after treatment and compared these with brain activity in 62 age-matched children without stress.
Children with anxiety showed greater activity in several brain regions, including cortical areas in the frontal and parietal lobes, which are important for cognitive and regulatory functions such as attention and emotion regulation. The researchers also observed increased activity in deeper limbic regions such as the amygdala, which are essential for generating strong emotions such as anxiety and fear.
After three months of CBT treatment, children with anxiety showed a clinically significant reduction in anxiety symptoms and improved functioning. The increased activation observed before treatment in several frontal and parietal brain regions also improved after CBT, decreasing to levels equal to or lower than those of non-anxious children. According to the researchers, reduced activation in these brain regions may reflect more effective engagement of cognitive control networks after CBT.
However, eight brain regions, including the right amygdala, continued to show higher activity in the anxious children compared to the non-anxious children after treatment. This persistent pattern of enhanced activation suggests that certain brain regions, particularly limbic regions that modulate responses to anxiety-inducing stimuli, may be less responsive to the acute effects of CBT. Altering activity in these regions may require longer duration of CBT, additional forms of treatment, or direct targeting of subcortical brain regions.
“Understanding the brain circuitry that underpins feelings of intense anxiety and determining which circuits normalize and which do not improve with CBT is critical to advancing treatment and making it more effective for all children,” said first author Simone Haller, Ph.D. , Director of Research and Analysis at the NIMH Neuroscience and Neotherapeutics Unit.
In this study, all children with anxiety received CBT. For comparison, the researchers also measured brain activity in a separate sample of 87 youngsters who were at high risk for anxiety based on their infantile temperament (for example, they showed high sensitivity to new situations). Because these children had not been diagnosed with an anxiety disorder, they had not received CBT treatment. Their brain scans were done at ages 10 and 13.
In adolescents at idiosyncratic risk for anxiety, higher brain activity was associated with increased anxiety symptoms over time and matched brain activity seen in children diagnosed with an anxiety disorder before treatment. This provides preliminary evidence that brain changes in children with anxiety are due to CBT and may provide a reliable neural marker for treating anxiety.
Anxiety disorders are common in children and can cause them significant distress in social and academic situations. They are also chronic, with a strong connection to adulthood when they become more difficult to deal with. Despite the effectiveness of CBT, many children continue to experience anxiety symptoms after treatment. Enhancing treatment to more effectively address childhood stress can have short- and long-term benefits and prevent more serious problems later in life.
This study provides evidence—in a large cohort of unmedicated youth with anxiety disorders—of altered brain circuits underlying CBT treatment effects. The findings could, in time, be used to improve treatment outcomes by targeting brain circuits linked to clinical improvement. This is particularly important for the subset of children who did not improve significantly after short-term CBT.
“The next step for this research is to understand which children are most likely to respond. Are there factors we can assess before treatment begins to make the most informed decisions about who should receive what treatment and when? Answering these questions will further translate our research findings into clinical practice,” said Brotman.
Report
Haller, SP, Linke, JO, Grassie, HL, Jones, EL, Pagliaccio, D., Harrewijn, A., White, LK, Naim, R., Abend, R., Mallidi, A., Berman, E., Lewis, KM, Kircanski, K., Fox, NA, Silverman, WK, Kalin, NH, Bar-Haim, Y., & Brotman, MA (2024). Normalization of fronto-parietal activation by cognitive-behavioral therapy in unmedicated pediatric patients with anxiety disorders. American Journal of Psychiatry. https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.20220449
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