Neuroplasticity in Response to Cognitive Behavior Therapy for Social Anxiety Disorder

Background: Functional magnetic resonance imaging studies have consistently showed increased amygdala responsiveness in Social Anxiety Disorder (SAD), which decreases after anxiolytic treatment (e.g., Cognitive Behavior Therapy, CBT). However, less is known about treatment-related structural gray matter (GM) volume changes. Furthermore, the relationship between functional and structural plasticity are largely neglected in the literature. Methods: Functional and structural neuroimaging were used to assess 26 SAD patients. The patients were randomized to receive Internet-delivered CBT (ICBT), or a control condition. The Clinical Global Impression-Improvement scale (CGI-I) determined clinical response. Also, we assessed level of anticipatory speech anxiety. At pre-, and post-treatment, blood-oxygen-level dependent (BOLD) responses to self-referential criticism were recorded, and structural data was examined with voxel-based morphometry (VBM). Results: CGI-I assessment showed that eight (61%) patients were deemed as responders following ICBT, and 3 (23%) in the control group (χ2=3.90, p=0.047). Time ˙ treatment interactions showed decreased amygdala BOLD response (Z=3.28, p=0.015, Family Wise-Error corrected, FWE), and amygdala GM volume (Z=3.30, pFWE=0.024) after ICBT. At baseline, GM amygdala volume was correlated with anticipatory anxiety (Z=2.96, pFWE=0.040), and amygdala GM atrophy following ICBT was correlated with decreased anticipatory anxiety (Z>2.83, pFWE<0.055). Moreover, the amygdala BOLD response change was associated with the local GM atrophy after ICBT (Z>2.45, pFWE<0.029). Conclusions: This is the first randomized study to evaluate multiple imaging modalities and the brain´s plasticity to an anxiolytic treatment. The functional and structural plasticity was highly correlated as indicated by anxiety-related BOLD signal change and GM volume in the amygdala following ICBT