RATIONALE: The amygdala and insular cortex are integral to the processing of emotionally salient stimuli. We have shown in healthy volunteers that an anxiolytic agent, lorazepam, dose-dependently attenuates activation of limbic structures. OBJECTIVE: The current study investigated whether administration of a selective serotonin reuptake inhibitor (SSRI), escitalopram, alters the activation of limbic structures. We hypothesized that subchronic (21 days) SSRI treatment attenuates the activation of the amygdala and insula during processing of emotional faces. MATERIALS AND METHODS:Thirteen healthy volunteers participated in a double-blind, placebo-controlled, crossover, randomized study. After 21 days of treatment with either escitalopram or placebo, participants underwent functional magnetic resonance imaging (fMRI) during which all subjects completed an emotion face assessment task, which has been shown to elicit amygdala and insula activation. RESULTS: Subjects activated the bilateral insula and amygdala after treatment with both escitalopram and placebo. In subjects who were adherent to the protocol (as evidenced by sufficiently high urine concentrations of escitalopram), a reduction in amygdala activation was seen in the escitalopram condition compared to placebo. CONCLUSION: The current investigation provides further evidence for the mechanism of action of SSRIs through the attenuation of activation in brain regions responsible for emotion processing and provides support for the use of blood oxygenation level-dependent fMRI with pharmacological probes to help identify the specific therapeutic effect of these agents in patients with anxiety and mood disorders.
RCT Entities:
RATIONALE: The amygdala and insular cortex are integral to the processing of emotionally salient stimuli. We have shown in healthy volunteers that an anxiolytic agent, lorazepam, dose-dependently attenuates activation of limbic structures. OBJECTIVE: The current study investigated whether administration of a selective serotonin reuptake inhibitor (SSRI), escitalopram, alters the activation of limbic structures. We hypothesized that subchronic (21 days) SSRI treatment attenuates the activation of the amygdala and insula during processing of emotional faces. MATERIALS AND METHODS: Thirteen healthy volunteers participated in a double-blind, placebo-controlled, crossover, randomized study. After 21 days of treatment with either escitalopram or placebo, participants underwent functional magnetic resonance imaging (fMRI) during which all subjects completed an emotion face assessment task, which has been shown to elicit amygdala and insula activation. RESULTS: Subjects activated the bilateral insula and amygdala after treatment with both escitalopram and placebo. In subjects who were adherent to the protocol (as evidenced by sufficiently high urine concentrations of escitalopram), a reduction in amygdala activation was seen in the escitalopram condition compared to placebo. CONCLUSION: The current investigation provides further evidence for the mechanism of action of SSRIs through the attenuation of activation in brain regions responsible for emotion processing and provides support for the use of blood oxygenation level-dependent fMRI with pharmacological probes to help identify the specific therapeutic effect of these agents in patients with anxiety and mood disorders.
Authors: Robert D Rogers; Elizabeth M Tunbridge; Zubin Bhagwagar; Wayne C Drevets; Barbara J Sahakian; Cameron S Carter Journal: Neuropsychopharmacology Date: 2003-01 Impact factor: 7.853
Authors: S McKie; C Del-Ben; R Elliott; S Williams; N del Vai; I Anderson; J F W Deakin Journal: Psychopharmacology (Berl) Date: 2005-05-12 Impact factor: 4.530
Authors: Birgit Völlm; Paul Richardson; Shane McKie; Rebecca Elliott; J F W Deakin; Ian M Anderson Journal: Eur J Neurosci Date: 2006-01 Impact factor: 3.386
Authors: Cristina M Del-Ben; J F William Deakin; Shane McKie; Nicola A Delvai; Steve R Williams; Rebecca Elliott; Mairead Dolan; Ian M Anderson Journal: Neuropsychopharmacology Date: 2005-09 Impact factor: 7.853
Authors: Catherine J Harmer; Clare E Mackay; Catriona B Reid; Philip J Cowen; Guy M Goodwin Journal: Biol Psychiatry Date: 2006-02-07 Impact factor: 13.382
Authors: Alan N Simmons; Murray B Stein; Irina A Strigo; Estibaliz Arce; Carla Hitchcock; Martin P Paulus Journal: Hum Brain Mapp Date: 2010-12-22 Impact factor: 5.038
Authors: Robin L Aupperle; Lakshmi Ravindran; Dharol Tankersley; Taru Flagan; Nathan R Stein; Alan N Simmons; Murray B Stein; Martin P Paulus Journal: Neuropsychopharmacology Date: 2011-03-23 Impact factor: 7.853
Authors: Daniel H Wolf; Theodore D Satterthwaite; James Loughead; Amy Pinkham; Eve Overton; Mark A Elliott; Gersham W Dent; Mark A Smith; Ruben C Gur; Raquel E Gur Journal: Psychopharmacology (Berl) Date: 2011-05-21 Impact factor: 4.530