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. 2023 Nov 27;24(1):761.
doi: 10.1186/s13063-023-07788-x.

Effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing using task-based fMRI in healthy subjects and patients with major depressive disorder - study protocol for a randomized clinical trial

Luisa Carstens #  1 , Margot Popp #  2 , Christian Keicher  3 , Rita Hertrampf  3 , David Weigner  1 , Marvin S Meiering  4 , Gerd Luippold  5 , Sigurd D Süssmuth  6 , Christian F Beckmann  7   8   9 , Andreas Wunder #  2 , Simone Grimm #  1
Affiliations

Effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing using task-based fMRI in healthy subjects and patients with major depressive disorder - study protocol for a randomized clinical trial

Luisa Carstens et al. Trials. .

Abstract

Background: Anhedonia and other deficits in reward- and motivation-related processing in psychiatric patients, including patients with major depressive disorder (MDD), represent a high unmet medical need. Neurobiologically, these deficits in MDD patients are mainly associated with low dopamine function in a frontostriatal network. In this study, alterations in brain activation changes during reward processing and at rest in MDD patients compared with healthy subjects are explored and the effects of a single low dose of the dopamine D2 receptor antagonist amisulpride are investigated.

Methods: This is a randomized, controlled, double-blind, single-dose, single-center parallel-group clinical trial to assess the effects of a single dose of amisulpride (100 mg) on blood-oxygenation-level-dependent (BOLD) responses during reward- and motivation-related processing in healthy subjects (n = 60) and MDD patients (n = 60). Using functional magnetic resonance imaging (fMRI), BOLD responses are assessed during the monetary incentive delay (MID) task (primary outcome). Exploratory outcomes include BOLD responses and behavioral measures during the MID task, instrumental learning task, effort-based decision-making task, social incentive delay task, and probabilistic reward task as well as changes in resting state functional connectivity and cerebral blood flow.

Discussion: This study broadly covers all aspects of reward- and motivation-related processing as categorized by the National Institute of Mental Health Research Domain Criteria and is thereby an important step towards precision psychiatry. Results regarding the immediate effects of a dopaminergic drug on deficits in reward- and motivation-related processing not only have the potential to significantly broaden our understanding of underlying neurobiological processes but might eventually also pave the way for new treatment options.

Trial registration: ClinicalTrials.gov NCT05347199. April 12, 2022.

Keywords: Amisulpride; Anhedonia; Effort-based decision-making task; Instrumental learning task; Major depressive disorder; Monetary incentive delay task; Probabilistic reward task; Resting state; Social incentive delay task; fMRI.

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Conflict of interest statement

MP, GL, and AW are employees of Boehringer Ingelheim Pharma GmbH & Co. KG. SDS is full-time employee of Boehringer Ingelheim International GmbH and a member of the Faculty of Medicine of Ulm University without conflicts of interest. LC, CK, RH, DW, MSM, and SG declare no competing interests. CFB is the founder and shareholder of SBGneuro Ltd.

Figures

Fig. 1
Fig. 1
Timeline for substance administration and MRI protocol for each experimental group at visit 3 and visit 4
See this image and copyright information in PMC

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