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Aberrant brain responses to emotionally valent words is normalised after cognitive behavioural therapy in female depressed adolescents

Chuang, Jie-Yu and Whitaker, Kirstie J. and Murray, Graham K. and Elliott, Rebecca and Hagan, Cindy C. and Graham, Julia M. E. and Ooi, Cinly and Tait, Roger and Holt, Rosemary J. and van Nieuwenhuizen, Adrienne O. and Reynolds, Shirley and Wilkinson, Paul O. and Bullmore, Edward T. and Lennox, Belinda R. and Sahakian, Barbara J. and Goodyer, Ian and Suckling, John (2016) Aberrant brain responses to emotionally valent words is normalised after cognitive behavioural therapy in female depressed adolescents. Journal of Affective Disorders, 189 . pp. 54-61. ISSN 0165-0327. PMCID PMC4650987. doi:10.1016/j.jad.2015.09.008.

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Background: Depression in adolescence is debilitating with high recurrence in adulthood, yet its pathophysiological mechanism remains enigmatic. To examine the interaction between emotion, cognition and treatment, functional brain responses to sad and happy distractors in an affective go/no-go task were explored before and after Cognitive Behavioural Therapy (CBT) in depressed female adolescents, and healthy participants. Methods: Eighty-two Depressed and 24 healthy female adolescents, aged 12–17 years, performed a functional magnetic resonance imaging (fMRI) affective go/no-go task at baseline. Participants were instructed to withhold their responses upon seeing happy or sad words. Among these participants, 13 patients had CBT over approximately 30 weeks. These participants and 20 matched controls then repeated the task. Results: At baseline, increased activation in response to happy relative to neutral distractors was observed in the orbitofrontal cortex in depressed patients which was normalised after CBT. No significant group differences were found behaviourally or in brain activation in response to sad distractors. Improvements in symptoms (mean: 9.31, 95% CI: 5.35–13.27) were related at trend-level to activation changes in orbitofrontal cortex. Limitations: In the follow-up section, a limited number of post-CBT patients were recruited. Conclusions: To our knowledge, this is the first fMRI study addressing the effect of CBT in adolescent depression. Although a bias toward negative information is widely accepted as a hallmark of depression, aberrant brain hyperactivity to positive distractors was found and normalised after CBT. Research, assessment and treatment focused on positive stimuli could be a future consideration. Moreover, a pathophysiological mechanism distinct from adult depression may be suggested and awaits further exploration.

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Hagan, Cindy C.0000-0002-4576-7120
Additional Information:© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( Received 25 June 2015, Revised 10 August 2015, Accepted 5 September 2015, Available online 11 September 2015. We appreciate technical help from Dr. Peter Watson, Mr. Andrew Jahn, Dr. Gonzalo Arrondo, Dr. Jeanette Mumford, Dr. Anderson M. Winkler, Dr. Zheng Ye, and Dr. Stuart Rankin. This work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (, provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council. The study was funded by the Medial Research Council (grant: G0802226). The IMPACT clinical trial was funded by the NHS Health Technology Assessment (HTA) Programme, Central Manchester and Manchester Children's University Hospitals NHS Trust, and the Cambridge and Peterborough Mental Health Trust. Additional support was provided by the jointly funded Medical Research Council/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. Contributors: SR, ETB, BRL, BJS, IG, JS conceived and designed the experiment. CCH, JMEG, RJH, AON collected the data. JC, KW, GM, CO, RT analysed the data. JC, JS, RE drafted the manuscript. All authors critically reviewed the manuscript. Conflict of interest: Professor Sahakian reports personal fees from Cambridge Cognition, personal fees and other from Lundbeck, personal fees from Servier, grants from J&J Janssen, other from Otsuka, personal fees from Peak (Brainbow), outside the submitted work; Professor Bullmore works half-time for the Univeristy of Cambridge and half-time for GlaxoSmithKline. He holds stock in GlaxoSmithKline. Professor Goodyer reports personal fees from Lundbeck and holds grants from the Wellcome Trust and the Friends of Peterhouse Charity and NIHR-HTA. Dr. Wilkinson reports grants from MRC during the conduct of the study; personal fees from Lundbeck, personal fees from Takeda, outside the submitted work; and acts as a supervisor and trainer for interpersonal psychotherapy.
Funding AgencyGrant Number
Higher Education Funding Council for EnglandUNSPECIFIED
Science and Technology Facilities Council (STFC)UNSPECIFIED
Medical Research Council (UK)G0802226
National Health Service TrustUNSPECIFIED
Cambridge and Peterborough Mental Health TrustUNSPECIFIED
National Institute for Health ResearchUNSPECIFIED
Subject Keywords:Adolescent depression; Functional magnetic resonance imaging; Cognitive behaviour therapy; Positive stimuli
PubMed Central ID:PMC4650987
Record Number:CaltechAUTHORS:20200225-135945558
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Official Citation:Jie-Yu Chuang, Kirstie J Whitaker, Graham K Murray, Rebecca Elliott, Cindy C Hagan, Julia ME Graham, Cinly Ooi, Roger Tait, Rosemary J Holt, Adrienne O van Nieuwenhuizen, Shirley Reynolds, Paul O Wilkinson, Edward T Bullmore, Belinda R Lennox, Barbara J Sahakian, Ian Goodyer, John Suckling, Aberrant brain responses to emotionally valent words is normalised after cognitive behavioural therapy in female depressed adolescents, Journal of Affective Disorders, Volume 189, 2016, Pages 54-61, ISSN 0165-0327,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101565
Deposited By: George Porter
Deposited On:26 Feb 2020 15:41
Last Modified:16 Nov 2021 18:03

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