title: Amygdala-frontal couplings characterizing SSRI and placebo response in social anxiety disorder.
abstract: In patients with social anxiety disorder (SAD) it has been reported that selective serotonin reuptake inhibitors (SSRIs) and placebo induce anxiolytic effects by attenuating neural activity in overlapping amygdala subregions, i.e. left basolateral and right ventrolateral amygdala. However, it is not known whether these treatments inhibit amygdala subregions via similar or distinct brain pathways. As anxiolytic treatments may alter amygdala-frontal couplings we investigated differences and similarities in amygdala-frontal functional co-activation patterns between responders and nonresponders to SSRIs and placebo in patients with SAD. Positron emission tomography (PET) with oxygen-15-labeled water was used to measure anxiety-related regional cerebral blood flow in 72 patients with SAD before and after 6-8 wk of treatment under double-blind conditions. Functional couplings were evaluated with a seed region approach using voxel values from the left basolateral and right ventrolateral amygdala. Responders and nonresponders to SSRIs and placebo showed different treatment-induced co-activations between the left amygdala and the dorsolateral prefrontal cortex (dlPFC) as well as the rostral anterior cingulate cortex (ACC). Conjunction analysis suggested shared anxiolysis-dependent inverse co-activations in SSRI and placebo responders between the left amygdala-dlPFC and left amygdala-rostral ACC, and a shared positive co-activation between left amygdala-dorsal ACC. We demonstrate that amygdala-frontal co-activation patterns differentiate effective from ineffective anxiolytic treatments and that SSRI and placebo responders share overlapping neuromodulatory paths that may underlie improved emotion regulation and reduced expression of anxiety.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00343707.
authors.affiliation: Department of Psychology,Uppsala University,Uppsala,Sweden.
authors.forename: Vanda
authors.initials: V
authors.lastname: Faria
authors.affiliation: Department of Psychology and Neuroscience,Duke University,Durham, NC,USA.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ahs
authors.affiliation: PET Centre, Uppsala University Hospital and Section of Nuclear Medicine and PET, Uppsala University,Uppsala,Sweden.
authors.forename: Lieuwe
authors.initials: L
authors.lastname: Appel
authors.affiliation: P.A.I.N. Group, Department of Anesthesia,Children's Hospital,Boston, MA,USA.
authors.forename: Clas
authors.initials: C
authors.lastname: Linnman
authors.affiliation: GlaxoSmithKline, Medicine Research Centre,Verona,Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bani
authors.affiliation: GlaxoSmithKline, Medicine Research Centre,Verona,Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bettica
authors.affiliation: GlaxoSmithKline, Medicine Research Centre,Verona,Italy.
authors.forename: Emilio Merlo
authors.initials: EM
authors.lastname: Pich
authors.forename: Kurt
authors.initials: K
authors.lastname: Wahlstedt
authors.affiliation: Department of Psychology,Uppsala University,Uppsala,Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Fredrikson
authors.affiliation: Department of Psychology,Uppsala University,Uppsala,Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Furmark
mesh_terms: D000679:Amygdala / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D006179:Gyrus Cinguli / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D015990:Placebo Effect; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014151:Anti-Anxiety Agents; D017367:Selective Serotonin Reuptake Inhibitors