A randomized controlled experimental medicine study of ghrelin in value-based decision making
Michal Pietrzak, … , Gustav Tinghög, Markus Heilig
Michal Pietrzak, … , Gustav Tinghög, Markus Heilig
Published April 11, 2023
Citation Information: J Clin Invest. 2023;133(12):e168260. https://doi.org/10.1172/JCI168260.
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Clinical Research and Public Health Metabolism

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

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 reward using monetary rewards.METHODS Thirty participants (50% women and 50% men) underwent 2 fMRI scans while receiving i.v. ghrelin or saline in a randomized counterbalanced order.RESULTS Striatal representations of reward anticipation were unaffected by ghrelin, while activity during anticipation of losses was attenuated. Temporal discounting rates of monetary reward 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 found that ghrelin did not affect sensitivity to monetary reward anticipation, but rather resulted in attenuated loss aversion and lower discounting rates for these rewards. Ghrelin may cause a motivational shift toward caloric reward rather than globally promoting the value of reward.TRIAL REGISTRATION EudraCT 2018-004829-82.FUNDING Swedish Research Council (2013-07434), Marcus and Marianne Wallenberg foundation (2014.0187) and National Institute on Drug Abuse/National Institute on Alcohol Abuse and Alcoholism Intramural Research Program.

Authors

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

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Figure 3

Behavioral results in the delay discounting task.

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Behavioral results in the delay discounting task. n = 23 (12 men and 11 ...
n = 23 (12 men and 11 women). (A) Main graph: fitted hyperbolic discounting functions under placebo (blue) and ghrelin (red) conditions; Inset: mean ± SEM and individual discounting constant k under the respective condition. (B) discounting constant for women only; (C) discounting constant for men only. There was a main effect of intervention (F[1,22]=11.8, P = 0.002, ηp2=0.35), a main effect of sex (F[1,22]=7.1, P = 0.014, ηp2=0.24), and a trend for an intervention × sex interaction (F[1,22]=3.2, P = 0.09, ηp2=0.13). Post-hoc Newman-Keuls tests indicated that, under the placebo condition, female participants had a steeper discounting (higher k value) than male participantss (P = 0.01); and that the main effect of treatment was driven by women (ghrelin versus placebo: female participants - P = 0.001; male participants – P = 0.26).