Researchers at the National Institutes of Health discovered overactivation in multiple brain regions, including the frontal and parietal lobes and the amygdala, in unmedicated children with anxiety disorders. They also demonstrated that cognitive behavioral therapy (CBT) improved clinical symptoms as well as brain function. The findings shed light on the brain mechanisms that underpin the immediate effects of cognitive behavioral therapy in treating one of the most common mental diseases. The study, published in the American Journal of Psychiatry, was led by experts from the National Institute of Mental Health.
“We know that 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 Novel Therapeutics Unit in the NIMH Intramural Research Program.
Sixty-nine unmedicated children diagnosed with an anxiety disorder underwent 12 weeks of CBT following 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.
We know that CBT is effective. These findings help us understand how CBT works, a critical first step in improving clinical outcomes.
Melissa Brotman
The researchers employed clinician-rated measures to compare children’s anxiety symptoms and clinical functioning before and after treatment. They also utilized task-based fMRI to examine whole-brain alterations before and after treatment, comparing them to brain activity in 62 similarly aged children who did not have anxiety.
Children with anxiety had higher levels of activity in several brain regions, including cortical areas in the frontal and parietal lobes, which are crucial for cognitive and regulatory processes like attention and emotion regulation. The researchers also noticed increased activity in deeper limbic areas such as the amygdala, which is responsible for creating intense emotions like worry and terror.
Following three months of CBT treatment, children with anxiety showed a clinically significant decrease in anxiety symptoms and improved functioning. Increased activation seen before treatment in many frontal and parietal brain regions also improved after CBT, declining to levels equal to or lower than those of non-anxious children. According to the researchers, the reduced activation in these brain areas may reflect more efficient engagement of cognitive control networks following CBT.
However, eight brain regions, including the right amygdala, continued to show higher activity in anxious compared to non-anxious children after treatment. This persistent pattern of enhanced activation suggests some brain regions, particularly limbic areas that modulate responses to anxiety-provoking stimuli, may be less responsive to the acute effects of CBT. Changing activity in these regions may require a longer duration of CBT, additional forms of treatment, or directly targeting subcortical brain areas.
“Understanding the brain circuitry underpinning feelings of severe anxiety and determining which circuits normalize and which do not as anxiety symptoms improve with CBT is critical for advancing treatment and making it more effective for all children,” said first author Simone Haller, Ph.D., Director of Research and Analytics in the NIMH Neuroscience and Novel Therapeutics Unit.
In this study, all children with anxiety received CBT. For comparison purposes, the researchers also measured brain activity in a separate sample of 87 youth who were at high risk for anxiety based on their infant temperament (for example, showing a high sensitivity to new situations). Because these children were not diagnosed with an anxiety disorder, they had not received CBT treatment. Their brain scans were taken at 10 and 13 years.
In adolescents at temperamental risk for anxiety, higher brain activity was related to increased anxiety symptoms over time and matched the brain activity seen in children diagnosed with an anxiety disorder before treatment. This provides preliminary evidence that the brain changes in children with anxiety were driven by CBT and that they may offer a reliable neural marker of anxiety treatment.
Anxiety disorders are common in children and can cause them significant distress in social and academic situations. They are also chronic, with a strong link into adulthood when they become harder to treat. Despite the effectiveness of CBT, many children continue to show anxiety symptoms after treatment. Enhancing the therapy to treat anxiety more effectively during childhood can have short- and long-term benefits and prevent more serious problems later in life.
In a large cohort of unmedicated kids with anxiety disorders, this study found evidence of changed brain circuitry behind CBT treatment benefits. The discoveries could eventually be utilized to improve treatment outcomes by focusing on brain circuits associated with clinical improvement. This is especially crucial for the subset of children who did not show substantial improvement after short-term CBT.
“The next stage in this research is determining which youngsters are most likely to respond. Are there any factors we can consider before starting therapy in order to make the best decisions about who should receive which treatment and when? “Answering these questions would help us translate our research findings into clinical practice,” said Brotman.
