Fronto-parietal hyperactivation normalizes after CBT in youths with anxiety

Key takeaways:

• Activity among the anxiety group normalized in 13 regions of the fronto-parietal network regions after 12 weeks of CBT.
• Hyperactivity persisted after treatment in some cortical and subcortical regions.

Fronto-parietal activation and reaction time appeared to normalize following cognitive behavioral therapy among unmedicated youths with anxiety, according to a study published in American Journal of Psychiatry.

Still, researchers found that some cortical and subcortical regions remained hyperactive following CBT, suggesting that limbic regions may be less amenable to the effects of this therapy.

“Pediatric anxiety disorders are prevalent and highly impairing. Cognitive behavioral therapy is an effective first-line treatment,” Simone P. Haller, PhD, director of research and analytics in the Neuroscience and Novel Therapeutics Unit of NIMH, and colleagues wrote. “However, the neural mechanisms associated with CBT-related symptom change remain largely unknown. Elucidating changes in brain function following CBT is a first step toward providing mechanistic insights, modifying treatment and improving clinical outcomes.”

Haller and colleagues compared three groups of participants to identify the brain mechanisms that are affected by CBT.

The first group included 69 unmedicated youths with a primary anxiety disorder (mean age, 12.79 years; standard deviation [SD], 2.98; 33% male) who completed 12 sessions of CBT and underwent functional MRI (fMRI) scanning during a threat attention task before and after the treatment period (mean time between scans, 107.12 days; SD, 33.13).

The second group was a control with 62 healthy youths (mean age, 13.66 years; SD, 2.23; 48% male) who underwent fMRI scanning at the same intervals as the test group (mean time between scans, 84.1 days; SD = 35.38).

The third group included 87 youths (mean age, 10.51 years; SD = 0.43; 41% male) who had a temperamental risk for anxiety but did not participate in CBT. The purpose of this group was to determine whether neural differences related to anxiety would stay the same without treatment.

During weekly CBT sessions, the researchers administered the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Impressions Scale improvement scale (CGI-I) to track participants’ progress.

The anxiety group showed significant improvements in PARS scores (mean change, –4.15; SD = 4.19; P < .001) following treatment. CGI-I scores improved as well, with 66% being considered responsive based on a posttreatment score of 3 or lower.

In terms of behavioral effects, youth in the anxiety group showed significantly slower response times across conditions relative to the control group at the pretreatment scan (P < .001), with the difference persisting but to a lesser degree at the posttreatment scan (P = .03).

Whole-brain analyses of fMRI scans revealed 37 clusters with significant group-by-time-point interaction.

In 13 of these regions — which included fronto-parietal network regions — the anxiety group showed activity normalization following treatment, whereas there were no differences in the control group before and after treatment.

Another eight regions showed hyperactivation in the anxiety group that did not change significantly following treatment. These regions included the left and right motor cortex, the right amygdala/parahippocampal gyrus and lateral anterior frontal areas.

In both scans, the at-risk group showed similar activity to the anxiety group before treatment. These results indicate that the changes seen in the anxiety group were related to treatment, according to Haller and colleagues.

“The data from this study reveal neural mechanisms that change following the acute effects of CBT for pediatric anxiety, as well as potential subcortical and cortical targets that remain dysfunctional after 12 weeks of CBT,” they wrote. “Future work may benefit from directly targeting subcortical, automatic and biased processing to enhance CBT treatment response.”