Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, Oxford, UK.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
J Psychopharmacol. 2023 Apr;37(4):420-431. doi: 10.1177/02698811221144636. Epub 2023 Jan 11.
Dysfunction of dopaminergic pathways has been considered to play a pivotal role in Parkinson's disease (PD), affecting the processing of emotional and rewarding information, and potentially leading to symptoms of depression or apathy. However, some aspects of motivation in PD might be affected by non-dopaminergic mechanisms.
The objective of this experimental medicine study was to investigate the contribution of serotonergic modulation via administration of citalopram (20 mg) for 7 days on motivated decision-making in twenty PD patients, measured using several different computerised tasks and clinical questionnaires that probe different aspects of decision-making. Twenty healthy controls were additionally tested without medication to assess any baseline differences between the two groups.
Results indicated that PD patients were overall less motivated than controls on an effort- and reward-based decision-making task. Citalopram increased or decreased willingness to exert effort for reward, depending on whether baseline motivation was high or low, respectively. A task assessing decision-making under risk revealed higher levels of risk aversion for potential losses in PD patients, which neither serotonin nor the patient's regular dopaminergic medication seemed to restore. However, citalopram in PD was associated with more risk-seeking choices for gains, although patients and controls did not differ on this at baseline.
The results provide evidence for a role of the serotonergic system in influencing some aspects of motivated decision-making in PD processes.
多巴胺能通路的功能障碍被认为在帕金森病（PD）中起着关键作用，影响情绪和奖励信息的处理，并可能导致抑郁或冷漠的症状。然而，PD 中的某些动机方面可能受到非多巴胺能机制的影响。
这项实验医学研究的目的是通过在二十名 PD 患者中使用几种不同的计算机化任务和临床问卷来研究 7 天的西酞普兰（20mg）给药对动机决策的 5-羟色胺调节的贡献，这些问卷探查决策的不同方面。另外还对二十名健康对照者进行了未经药物治疗的测试，以评估两组之间的任何基线差异。
结果表明，与对照组相比，PD 患者在基于努力和奖励的决策任务中总体上的动机较低。西酞普兰根据基线动机的高低，分别增加或减少了对奖励的努力意愿。评估风险下决策的任务显示，PD 患者对潜在损失的风险规避程度更高，而 5-羟色胺和患者的常规多巴胺能药物似乎都无法恢复这种情况。然而，PD 中的西酞普兰与收益的更多风险寻求选择相关，尽管患者和对照组在这方面的基线没有差异。
结果提供了证据表明 5-羟色胺系统在影响 PD 过程中某些方面的动机决策方面起着作用。
