Dopaminergic drugs decrease loss aversion in Parkinson’s disease with but not without depression

Acknowledgements This project was funded by a grant from the " Stichting Parkinson Fonds " , Hoofddorp, the Netherlands. We would like to thank all participants for their cooperation in the study. Abstract 1 Depression, a common non-motor symptom of Parkinson's disease (PD), is accompanied by impaired 2 decision making and an enhanced response to aversive outcomes. Current strategies to treat depression 3 in PD include dopaminergic medication. However, their use can be accompanied by detrimental side 4 effects, such as enhanced risky choice. The mechanisms underlying dopamine-induced increases in risky 5 choice are unclear. In the current study we adopt a clinical-neuroeconomic approach to investigate the 6 effects of dopaminergic medication on loss aversion during risky choice in depressed and non-depressed 7 PD. Twenty-three healthy controls, 21 depressed and 22 non-depressed PD patients were assessed using 8 a well-established gambling task measuring loss aversion during risky choice. Patients were tested on 9 two occasions, after taking their normal dopaminergic medication (ON) and after withdrawal of their 10 medication (OFF). Dopaminergic medication decreased loss aversion to a greater extent in depressed 11 than non-depressed PD patients. Moreover, we show that the degree to which dopaminergic 12 medication decreases loss aversion correlated with current depression severity and with drug effects on 13 depression scores. These findings demonstrate that dopamine-induced changes in loss aversion depend 14 on the presence of depressive symptoms in PD. 17 Dopaminergic medication that is used to treat motor and non-motor symptoms in patients with 18 Parkinson's disease is known to contribute to risky decision-making. The underlying mechanisms are 19 unclear. The present study demonstrates that dopaminergic medication in Parkinson's disease 20 decreases loss aversion during risky choice, but only in depressed and not in non-depressed patients 21 with Parkinson's disease. These results advance our understanding of the mechanisms underlying 22 dopamine-induced risky choice, while also identifying depression as an important factor that confers 23 vulnerability to such dopamine-induced risky choice. 24 peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.