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Published May 10, 2022 | Published + Supplemental Material
Journal Article Open

Neural, physiological, and psychological markers of appetitive conditioning in anorexia nervosa: a study protocol


Background. Anorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations—a critical component of hedonic responding—has never been studied in AN. Methods. This multi-modal study will employ a 2-day Pavlovian appetitive conditioning paradigm to interrogate the (1) acquisition, (2) extinction, (3) spontaneous recovery and (4) reinstatement of appetitive learning in adolescents and young adults with AN. Participants will be 30 currently ill, underweight individuals with AN; 30 weight-restored individuals with AN; and 30 age-matched healthy controls, all aged 12–22 years. All subjects will undergo clinical assessment, followed by the 2-day appetitive conditioning task during which fMRI, pupillometry, heart rate deceleration, and subjective ratings will be acquired. Discussion. This study will be the first to interrogate appetitive conditioning in AN—a disorder characterized by altered hedonic responding to food. Results will help establish objective biomarkers of appetitive conditioning in AN and lay the groundwork for developing novel lines of treatment for AN and other psychiatric disorders involving diminished ability to experience pleasure and reward. Trial registration: Pending. Intended registry: Clinicaltrials.gov.

Additional Information

© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Acknowledgements: Not applicable. Study stage: Data collection has not started. Funding for this study is provided by the Klarman Family Foundation, a private foundation where grants are competitively reviewed and funded. The funding source did not play a role in designing the study. Contributions. S.B.M. and J.D.F. led the manuscript development, and will coordinate the study, and are responsible for its methodological design. In addition, S.B.M. and J.D.F. will oversee all diagnostic assessments. S.B.M., J.D.F., T.D.Z. and M.C. developed and pilot tested the appetitive conditioning paradigm. S.B.M., J.D.F., R.T., A.A.B., and J.O.D. developed the neuroimaging analysis plan. M.S. provided critical feedback on the methodological design of the study. All authors read, edited and approved the final manuscript. Ethics approval and consent to participate. Ethics approval for this project was granted by the Institutional Review Boards at the University of Toronto; the University of California, Los Angeles; and at the University of Southern California. JDF and the research assistants at the University of Toronto will obtain informed consent and assent from potential trial participants. All participants in the study must sign a written consent form, or a written assent form, alongside a signed parent/guardian consent form, prior to participation. Consent for publication. Not applicable. The authors declare that they have no competing interests.

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August 22, 2023
October 24, 2023