Tim Outhred1, Pritha Das2, Kim L Felmingham3, Richard A Bryant4, Pradeep J Nathan5, Gin S Malhi2, Andrew H Kemp6. 1. Discipline of Psychiatry, Sydney Medical School, University of Sydney, Royal North Shore Hospital, Australia SCAN Research and Teaching Unit, School of Psychology, University of Sydney, Australia. 2. Discipline of Psychiatry, Sydney Medical School, University of Sydney, Royal North Shore Hospital, Australia CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, Australia Advanced Research and Clinical Highfield Imaging (ARCHI), University of Sydney, Royal North Shore Hospital, Australia. 3. School of Psychology, University of Tasmania, Hobart, Australia. 4. School of Psychology, University of New South Wales, Kensington, Australia. 5. Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom School of Psychology and Psychiatry, Monash University, Australia. 6. Discipline of Psychiatry, Sydney Medical School, University of Sydney, Royal North Shore Hospital, Australia SCAN Research and Teaching Unit, School of Psychology, University of Sydney, Australia CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, Australia Advanced Research and Clinical Highfield Imaging (ARCHI), University of Sydney, Royal North Shore Hospital, Australia University Hospital, University of São Paulo, São Paulo SP, Brazil.
Abstract
BACKGROUND: Acute neural effects of antidepressant medication on emotion processing biases may provide the foundation on which clinical outcomes are based. Along with effects on positive and negative stimuli, acute effects on neutral stimuli may also relate to antidepressant efficacy, yet these effects are still to be investigated. The present study therefore examined the impact of a single dose of the selective serotonin reuptake inhibitor escitalopram (20 mg) on positive, negative and neutral stimuli using pharmaco-fMRI. METHODS: Within a double-blind, randomized, placebo-controlled crossover design, healthy women completed 2 sessions of treatment administration and fMRI scanning separated by a 1-week washout period. RESULTS: We enrolled 36 women in our study. When participants were administered escitalopram relative to placebo, left amygdala activity was increased and right inferior frontal gyrus (IFG) activity was decreased during presentation of positive pictures (potentiation of positive emotion processing). In contrast, escitalopram was associated with decreased left amygdala and increased right IFG activity during presentation of negative pictures (attenuation of negative emotion processing). In addition, escitalopram decreased right IFG activity during the processing of neutral stimuli, akin to the effects on positive stimuli (decrease in negative appraisal). LIMITATIONS: Although we used a women-only sample to reduce heterogeneity, our results may not generalize to men. Potential unblinding, which was related to the subjective occurrence of side effects, occurred in the study; however, manipulation check analyses demonstrated that results were not impacted. CONCLUSION: These novel findings demonstrate that a single dose of the commonly prescribed escitalopram facilitates a positive information processing bias. These findings provide an important lead for better understanding effects of antidepressant medication.
RCT Entities:
BACKGROUND: Acute neural effects of antidepressant medication on emotion processing biases may provide the foundation on which clinical outcomes are based. Along with effects on positive and negative stimuli, acute effects on neutral stimuli may also relate to antidepressant efficacy, yet these effects are still to be investigated. The present study therefore examined the impact of a single dose of the selective serotonin reuptake inhibitor escitalopram (20 mg) on positive, negative and neutral stimuli using pharmaco-fMRI. METHODS: Within a double-blind, randomized, placebo-controlled crossover design, healthy women completed 2 sessions of treatment administration and fMRI scanning separated by a 1-week washout period. RESULTS: We enrolled 36 women in our study. When participants were administered escitalopram relative to placebo, left amygdala activity was increased and right inferior frontal gyrus (IFG) activity was decreased during presentation of positive pictures (potentiation of positive emotion processing). In contrast, escitalopram was associated with decreased left amygdala and increased right IFG activity during presentation of negative pictures (attenuation of negative emotion processing). In addition, escitalopram decreased right IFG activity during the processing of neutral stimuli, akin to the effects on positive stimuli (decrease in negative appraisal). LIMITATIONS: Although we used a women-only sample to reduce heterogeneity, our results may not generalize to men. Potential unblinding, which was related to the subjective occurrence of side effects, occurred in the study; however, manipulation check analyses demonstrated that results were not impacted. CONCLUSION: These novel findings demonstrate that a single dose of the commonly prescribed escitalopram facilitates a positive information processing bias. These findings provide an important lead for better understanding effects of antidepressant medication.
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