title: Amygdala subregions tied to SSRI and placebo response in patients with social anxiety disorder.
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.
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden. vanda.faria@psyk.uu.se
authors.forename: Vanda
authors.initials: V
authors.lastname: Faria
authors.forename: Lieuwe
authors.initials: L
authors.lastname: Appel
authors.forename: Fredrik
authors.initials: F
authors.lastname: Åhs
authors.forename: Clas
authors.initials: C
authors.lastname: Linnman
authors.forename: Anna
authors.initials: A
authors.lastname: Pissiota
authors.forename: Örjan
authors.initials: Ö
authors.lastname: Frans
authors.forename: Massimo
authors.initials: M
authors.lastname: Bani
authors.forename: Paolo
authors.initials: P
authors.lastname: Bettica
authors.forename: Emilio M
authors.initials: EM
authors.lastname: Pich
authors.forename: Eva
authors.initials: E
authors.lastname: Jacobsson
authors.forename: Kurt
authors.initials: K
authors.lastname: Wahlstedt
authors.forename: Mats
authors.initials: M
authors.lastname: Fredrikson
authors.forename: Tomas
authors.initials: T
authors.lastname: Furmark
mesh_terms: D000328:Adult; D000679:Amygdala / Q000098:blood supply* / Q000000981:diagnostic imaging; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010698:Phobic Disorders / Q000188:drug therapy / Q000503:physiopathology*; D015990:Placebo Effect; D049268:Positron-Emission Tomography; D016032:Randomized Controlled Trials as Topic; D012039:Regional Blood Flow; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors