Abstract
The amygdala is a key structure in the pathophysiology of anxiety disorders, and a putative target for anxiolytic treatments. Selective serotonin reuptake inhibitors (SSRIs) and placebo seem to induce anxiolytic effects by attenuating amygdala responsiveness. However, conflicting amygdala findings have also been reported. Moreover, the neural profile of responders and nonresponders is insufficiently characterized and it remains unknown whether SSRIs and placebo engage common or distinct amygdala subregions or different modulatory cortical areas. We examined similarities and differences in the neural response to SSRIs and placebo in patients with social anxiety disorder (SAD). Positron emission tomography (PET) with oxygen-15-labeled water was used to assess regional cerebral blood flow (rCBF) in 72 patients with SAD during an anxiogenic public speaking task, before and after 6–8 weeks of treatment under double-blind conditions. Response rate was determined by the Clinical Global Impression-Improvement scale. Conjunction analysis revealed a common rCBF-attenuation from pre- to post-treatment in responders to SSRIs and placebo in the left basomedial/basolateral and right ventrolateral amygdala. This rCBF pattern correlated with behavioral measures of reduced anxiety and differentiated responders from nonresponders. However, nonanxiolytic treatment effects were also observed in the amygdala. All subgroups, including nonresponders, showed deactivation of the left lateral part of the amygdala. No rCBF differences were found between SSRI responders and placebo responders. This study provides new insights into the brain dynamics underlying anxiety relief by demonstrating common amygdala targets for pharmacologically and psychologically induced anxiety reduction, and by showing that the amygdala is functionally heterogeneous in anxiolysis.
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Acknowledgements
This work was supported by GlaxoSmithKline, the Swedish Research Council, the Swedish Council for Working Life and Social Research, and a grant from the Foundation of Science and Technology from the Portuguese Ministry of Science, Technology and Higher Education co-financed by the European Social funding. We thank all patients for their contribution to this study and the staff members of Uppsala PET centre and Quintiles for providing excellent research conditions.
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Massimo Bani, Paolo Bettica, and Emilio Merlo Pich were full-time employees at GlaxoSmithKline at the time of the design and conduct of this study. None of the other authors declare conflict of interest.
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Faria, V., Appel, L., Åhs, F. et al. Amygdala Subregions Tied to SSRI and Placebo Response in Patients with Social Anxiety Disorder. Neuropsychopharmacol 37, 2222–2232 (2012). https://doi.org/10.1038/npp.2012.72
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