J Psychiatry Neurosci 2014;39(4):267-75
Tim Outhred, BAppSci; Pritha Das, PhD; Kim L. Felmingham, PhD; Richard A. Bryant, PhD; Pradeep J. Nathan, PhD; Gin S. Malhi, PhD; Andrew H. Kemp, PhD
Outhred, Das, Malhi, Kemp — Discipline of Psychiatry, Sydney Medical School, University of Sydney, Royal North Shore Hospital, Australia; Outhred, Kemp — SCAN Research and Teaching Unit, School of Psychology, University of Sydney, Australia; Das, Malhi, Kemp — CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, Australia; Das, Malhi, Kemp — Advanced Research and Clinical Highfield Imaging (ARCHI), University of Sydney, Royal North Shore Hospital, Australia; Felmingham — School of Psychology, University of Tasmania, Hobart, Australia; Bryant — School of Psychology, University of New South Wales, Kensington, Australia; Nathan — Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Nathan — School of Psychology and Psychiatry, Monash University, Australia; Kemp — University Hospital, University of São Paulo, São Paulo SP, Brazil
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.
Submitted June 18, 2013; Revised Nov. 3, 2013, Jan. 7, 2014; Accepted Jan. 14, 2014.
Acknowledgements: This research was supported by an Australian Research Council Discovery Project Grant (DP0987332), a National Health and Medical Research Council (NHMRC) Project Grant (464863) and a NHMRC Career Development Award (571101) awarded to A.H. Kemp. We acknowledge the support and assistance of the local and international research students and laboratory volunteers throughout the project.
Competing interests: T. Outhred and A.H. Kemp are supported by an Australian Postgraduate Award and an International Research Professorship from the Universidade de São Paulo, respectively. P.J. Nathan is an employee at UCB Pharma and hold shares in the company. G.S.Malhi has received research support from Astra Zeneca, Eli Lilly, Organon, Pfizer, Servier and Wyeth. He has been a speaker for Astra – Zeneca, Eli Lilly, Janssen Cilag, Lundbeck, Pfizer, Ranbaxy, Servier and Wyeth. He has been a consultant for Astra Zeneca, Eli Lilly, Janssen Cilag, Lundbeck and Servier. None declared for P. Das, K.L. Felmingham and R.A. Bryant.
Contributors: A.H. Kemp acquired the funding to conduct the study. T. Outhred, P. Das, K.L. Felmingham, R.A. Bryant, G.S. Malhi and A.H. Kemp designed the study. T. Outhred, P. Das, G.S. Malhi and A.H. Kemp acquired and analyzed the data, which P.J. Nathan also analyzed. T. Outhred wrote the article, which all authors reviewed and approved for publication.
Correspondence to: A.H. Kemp, Centre for Clinical Research and Epidemiology, University Hospital, University of São Paulo, Av Lineu
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