Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder

K N T Månsson, A Salami, A Frick, P Carlbring, G Andersson, T Furmark, C-J Boraxbekk, K N T Månsson, A Salami, A Frick, P Carlbring, G Andersson, T Furmark, C-J Boraxbekk

Abstract

Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala, which can be normalized by effective treatment like cognitive behavior therapy (CBT). Mechanisms underlying the brain's adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations, but multimodal neuroimaging studies addressing structure-function interactions are currently missing. Here, we examined treatment-related changes in brain structure (gray matter (GM) volume) and function (blood-oxygen level dependent, BOLD response to self-referential criticism) in 26 participants with social anxiety disorder randomly assigned either to CBT or an attention bias modification control treatment. Also, 26 matched healthy controls were included. Significant time × treatment interactions were found in the amygdala with decreases both in GM volume (family-wise error (FWE) corrected P(FWE) = 0.02) and BOLD responsivity (P(FWE) = 0.01) after successful CBT. Before treatment, amygdala GM volume correlated positively with anticipatory speech anxiety (P(FWE)=0.04), and CBT-induced reduction of amygdala GM volume (pre-post) correlated positively with reduced anticipatory anxiety after treatment (P(FWE) ⩽ 0.05). In addition, we observed greater amygdala neural responsivity to self-referential criticism in socially anxious participants, as compared with controls (P(FWE) = 0.029), before but not after CBT. Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment (P=0.007). Thus, our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala, which could be essential for achieving anxiety reduction with CBT.

Figures

Figure 1
Figure 1
Changes in (a) amygdala GM volume and (b) amygdala BOLD response to self-referential criticism, sorted by treatment and hemisphere. The y-axis shows change in beta-weight values, and lower beta-weights correspond to reduced GM volume and BOLD responsivity over time (pre–post). Error bars represent s.e. ABM, attention bias modification; CBT, cognitive behavior therapy; FWE, family-wise error corrected P-value; GM, gray matter volume.
Figure 2
Figure 2
Brain-behavior correlations showing that (a) pre-treatment gray matter volume in the left amygdala was associated with enhanced levels of anticipatory speech anxiety, and (b and c) reduced amygdala gray matter volume (left and right respectively) was positively associated with improved symptoms of anticipatory speech anxiety after cognitive behavior therapy. Gray shading corresponds to 95% confidence intervals.
Figure 3
Figure 3
The mediation paths supported reduced gray matter volume as the mediator of the relation between diminished amygdala BOLD responsivity (predictor) and improved anticipatory speech anxiety after cognitive behavior therapy. GM, gray matter.

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