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Clinical MedicineIn-Press PreviewMetabolism Open Access | 10.1172/JCI168260

A randomized controlled experimental medicine study of ghrelin in value-based decision making

Michal Pietrzak,1 Adam Yngve,1 J. Paul Hamilton,1 Robin Kämpe,1 Rebecca Boehme,1 Anna Asratian,1 Emelie Gauffin,1 Andreas Löfberg,2 Sarah Gustavson,1 Emil Persson,3 Andrea J. Capusan,1 Lorenzo Leggio,4 Irene Perini,1 Gustav Tinghög,3 and Markus Heilig1

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Pietrzak, M. in: JCI | PubMed | Google Scholar

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Yngve, A. in: JCI | PubMed | Google Scholar

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

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1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Kämpe, R. in: JCI | PubMed | Google Scholar |

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

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1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Asratian, A. in: JCI | PubMed | Google Scholar |

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Gauffin, E. in: JCI | PubMed | Google Scholar

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Löfberg, A. in: JCI | PubMed | Google Scholar |

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Gustavson, S. in: JCI | PubMed | Google Scholar

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Persson, E. in: JCI | PubMed | Google Scholar

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Capusan, A. in: JCI | PubMed | Google Scholar |

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Leggio, L. in: JCI | PubMed | Google Scholar |

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Perini, I. in: JCI | PubMed | Google Scholar |

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Tinghög, G. in: JCI | PubMed | Google Scholar |

1Department of Clinical and Biomedical Sciences, Linkoping University, Linköping, Sweden

2Clinical and Experimental Medicine, Linkoping University, Linköping, Sweden

3Department of Management and Engineering, Linkoping University, Linköping, Sweden

4Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIH, Bethesda, United States of America

Find articles by Heilig, M. in: JCI | PubMed | Google Scholar |

Published April 11, 2023 - More info

J Clin Invest. https://doi.org/10.1172/JCI168260.
Copyright © 2023, Pietrzak et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 11, 2023 - Version history
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Abstract

BACKGROUND. The stomach-derived hormone ghrelin stimulates appetite, but the ghrelin receptor is also expressed in brain circuits involved in motivation and reward. We examined ghrelin effects on decision making beyond food or drug rewards, using monetary outcomes.

METHODS. Thirty participants (50% females) underwent two fMRI scans, in randomized counterbalanced order, while receiving intravenous ghrelin or saline.

RESULTS. Striatal representations of reward anticipation were unaffected by ghrelin, while activity during anticipation of losses was attenuated. Temporal discounting rates of monetary rewards were lower overall in the ghrelin condition, an effect driven by women. Discounting rates were inversely correlated with neural activity in a large cluster within the left parietal lobule that included the angular gyrus. Activity in an overlapping cluster was related to behavioral choices, and was suppressed by ghrelin.

CONCLUSION. This is to our knowledge the first human study to extend the understanding of ghrelin’s significance beyond the canonical feeding domain or in relation to addictive substances. Contrary to our hypothesis, we find that ghrelin does not affect sensitivity to monetary reward anticipation, but rather results in attenuated loss aversion and lower discounting rates for these rewards. Ghrelin may cause a motivational shift toward caloric rewards rather than globally promoting the value of rewards.

TRIAL REGISTRATION. EudraCT 2018-004829-82

FUNDING. Swedish Research Council (MH: 2013-07434) and Marcus and Marianne Wallenberg foundation (GT: 2014.0187). Author LL is supported by NIDA/NIAAA IRP

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