Optimizing Behavioral Paradigms to Facilitate Development of New Treatments for Anhedonia and Reward Processing Deficits in Schizophrenia and Major Depressive Disorder: Study Protocol

Amy C Bilderbeck*, Andreea Raslescu, Dennis Hernaus, Anja Hayen, Daniel Umbricht, Darrel Pemberton, Jane Tiller, Birgitte Søgaard, Anke Sambeth, Therese van Amelsvoort, Andreas Reif, Georgios Papazisis, Victor Pérez, Matilde Elices, Damien Maurice, Valérie Bertaina-Anglade, Gerard R Dawson, Stephane Pollentier

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Behavioral tasks focusing on different subdomains of reward processing may provide more objective and quantifiable measures of anhedonia and impaired motivation compared with clinical scales. Typically, single tasks are used in relatively small studies to compare cases and controls in one indication, but they are rarely included in larger multisite trials. This is due to limited systematic standardization as well as the challenges of deployment in international studies and stringent adherence to the high regulatory requirements for data integrity. The Reward Task Optimization Consortium (RTOC) was formed to facilitate operational implementation of reward processing tasks, making them suitable for use in future large-scale, international, multisite drug development studies across multiple indications. The RTOC clinical study aims to conduct initial optimization of a set of tasks in patients with major depressive disorder (MDD) or schizophrenia (SZ).
Methods: We will conduct a multicenter study across four EU countries. Participants (MDD = 37, SZ = 37, with ≤80 age- and gender-matched healthy volunteers) will attend a study visit comprising screening, self-report and clinically rated assessments of anhedonia and symptom severity, and three reward processing tasks; specifically, the Grip Strength Effort task, the Doors task, and the Reinforcement Learning Working Memory task. The Grip Strength Effort and Doors tasks include simultaneous electroencephalography/event-related potential recordings. Outcomes will be compared using a two-way group design of MDD and SZ with matched controls, respectively. Further analyses will include anhedonia assessment scores as covariates. Planned analyses will assess whether our findings replicate previously published data, and multisite deployment will be evaluated through assessments of quality and conduct. A subset of participants will complete a second visit, to assess test–retest reliability of the task battery.
Discussion: This study will evaluate the operational deployment of three reward processing tasks to the regulatory standards required for use in drug development trials. We will explore the potential of these tasks to differentiate patients from controls and to provide a quantitative marker of anhedonia and/or impaired motivation, establishing their usefulness as endpoints in multisite clinical trials. This study should demonstrate where multifaceted reward deficits are similar or divergent across patient populations
Original languageEnglish
Article number536112
Pages (from-to)1-13
Number of pages13
JournalFrontiers in Psychiatry
Publication statusPublished - 5 Nov 2020


  • anhedonia
  • impaired motivation
  • negative symptoms
  • reward processing
  • reward deficits
  • schizophrenia
  • depression

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