Monique HM Timmer | Search bioRxiv

bioRxiv2016

Reward learning deficits in Parkinson’s disease depend on depression

BackgroundDepression is one of the most common and debilitating non-motor symptoms of Parkinsons disease (PD). The neurocognitive mechanisms underlying depression in PD are unclear and treatment is often suboptimal.\n\nMethodsWe investigated the role of striatal dopamine in reversal learning from reward and punishment by combining a controlled medication withdrawal procedure with functional magnetic resonance imaging (fMRI) in 22 non-depressed PD patients and 19 PD patients with past or present PD-related depression.\n\nResultsPD patients with a PD-related depression (history) exhibited impaired reward versus punishment reversal learning as well as reduced reward versus punishment-related BOLD signal in the striatum (putamen) compared with non-depressed PD patients. No effects of dopaminergic medication were observed.\n\nConclusionsThe present findings demonstrate that impairments in reversal learning from reward versus punishment and associated reward-related striatal signalling depend on the presence of (a history of) depression in PD.

Neuroscience↗

bioRxiv2016

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

Depression, a common non-motor symptom of Parkinsons 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.\n\nSignificance statementDopaminergic medication that is used to treat motor and non-motor symptoms in patients with Parkinsons disease is known to contribute to risky decision-making. The underlying mechanisms are unclear. The present study demonstrates that dopaminergic medication in Parkinsons disease decreases loss aversion during risky choice, but only in depressed and not in non-depressed patients with Parkinsons 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.\n\nConflict of InterestThe authors declare no competing financial interests.

Neuroscience↗