@article {Timmer069047, author = {Monique H.M. Timmer and Guillaume Sescousse and Rianne A.J. Esselink and Payam Piray and Roshan Cools}, title = {Dopaminergic drugs decrease loss aversion in Parkinson{\textquoteright}s disease with but not without depression}, elocation-id = {069047}, year = {2016}, doi = {10.1101/069047}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Depression, a common non-motor symptom of Parkinson{\textquoteright}s disease (PD), is accompanied by impaired decision making and an enhanced response to aversive outcomes. Current strategies to treat depression in PD include dopaminergic medication. However, their use can be accompanied by detrimental side effects, such as enhanced risky choice. The mechanisms underlying dopamine-induced increases in risky choice are unclear. In the current study we adopt a clinical-neuroeconomic approach to investigate the effects of dopaminergic medication on loss aversion during risky choice in depressed and non-depressed PD. Twenty-three healthy controls, 21 depressed and 22 non-depressed PD patients were assessed using a well-established gambling task measuring loss aversion during risky choice. Patients were tested on two occasions, after taking their normal dopaminergic medication (ON) and after withdrawal of their medication (OFF). Dopaminergic medication decreased loss aversion to a greater extent in depressed than non-depressed PD patients. Moreover, we show that the degree to which dopaminergic medication decreases loss aversion correlated with current depression severity and with drug effects on depression scores. These findings demonstrate that dopamine-induced changes in loss aversion depend on the presence of depressive symptoms in PD.Significance statement Dopaminergic medication that is used to treat motor and non-motor symptoms in patients with Parkinson{\textquoteright}s disease is known to contribute to risky decision-making. The underlying mechanisms are unclear. The present study demonstrates that dopaminergic medication in Parkinson{\textquoteright}s disease decreases loss aversion during risky choice, but only in depressed and not in non-depressed patients with Parkinson{\textquoteright}s disease. These results advance our understanding of the mechanisms underlying dopamine-induced risky choice, while also identifying depression as an important factor that confers vulnerability to such dopamine-induced risky choice.Conflict of Interest The authors declare no competing financial interests.}, URL = {https://www.biorxiv.org/content/early/2016/08/11/069047}, eprint = {https://www.biorxiv.org/content/early/2016/08/11/069047.full.pdf}, journal = {bioRxiv} }