Table 2.
Summary of papers examining functional neuroimaging markers of placebo effects in patients with social anxiety disorder
| Reference | n | Interventions | Study duration | Treatment response definition | Imaging modality | Imaging measure | Clinical results | Imaging markers of placebo response or placebo mechanisms | |
|---|---|---|---|---|---|---|---|---|---|
| Experimental | Comparison | ||||||||
| Faria et al. (2012) | 72 | Citalopram or paroxetine | Placebo | 6-8 wk | CGI-I = 1 or 2 | PET | rCBF during a public speaking task at baseline and study end | Total of 57% of SSRI group responded vs 30% of placebo group | Both SSRI and placebo responders showed reductions in right ventrolateral amygdala and left basomedial/basolateral amygdala. The rCBF change correlated with clinical measures of anxiety. Placebo responders additionally showed increased rCBF in right brainstem/pons compared with placebo nonresponders. |
| Faria et al. (2014) | 72 | Citalopram or paroxetine | Placebo | 6-8 wk | CGI-I = 1 or 2 | PET | Functional connectivity during a public speaking task at baseline and study end | Total of 57% of SSRI group responded vs 30% of placebo group | Placebo responders showed greater negative correlation between left amygdala and left dorsolateral PFC vs placebo nonresponders. Placebo responders showed greater negative correlation between left amygdala and right ventromedial and dorsolateral PFC, and greater positive correlation between left amygdala and right dorsomedial PFC vs SSRI responders. |
| Faria et al. (2017) | 46 | “Overt” escitalopram | “Covert” escitalopram | 9 wk | LSAS-SR < 39 | fMRI | BOLD signal change and functional connectivity during emotional face matching task | “Overt” treatment significantly superior (d = .24 vs d = 1.13) | Increased reactivity to emotional faces in overt vs covert in bilateral posterior cingulate, left mid temporal gyrus, left inferior frontal gyrus. Covert group showed increased connectivity between amygdala and right posterior cingulate and right insula when viewing emotional faces compared with overt group. |
| Furmark et al. (2008) | 25 | Placebo | None | 8 wk | CGI-I = 1 or 2 | PET | rCBF during a public speaking task at baseline and study end. Changes in rCBF associated with genotype. | Total of 10 (40%) responded to placebo | rCBF significantly reduced in left amygdala in placebo responders vs nonresponders. Patients homozygous for the long allele of 5-HTTLPR and/or the G allele of the G-703T polymorphism in TPH2 exhibited a significantly greater reduction in amygdala activity vs heterozygotes. Mediation analysis showed that the change in rCBF in the amygdala mediated the effect of G-703T polymorphism on CGI-I score. |
Abbreviations: 5-HTTLPR, serotonin transporter-linked polymorphic region; BOLD, blood-oxygen-level-dependent imaging; CGI-I, Clinical Global Impression-Improvement scale; fMRI, functional magnetic resonance imaging; LSAS-SR, Liebowitz Social Anxiety scale; PET, positron emission tomography; PFC, prefrontal cortex; rCBF, regional cerebral blood flow; SSRI, selective serotonin reuptake inhibitor; TPH2, tryptophan hydroxylase-2.