Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
1] Department of Psychiatry Research, The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA [2] The Feinstein Institute for Medical Research, Manhasset, NY, USA [3] Department of Psychiatry, Hofstra University School of Medicine, Hempstead, NY, USA.
Neuropsychopharmacology. 2014 Jan;39(2):274-82. doi: 10.1038/npp.2013.177. Epub 2013 Jul 25.
We recently reported that the D2/D3 agonist pramipexole may have pro-cognitive effects in euthymic patients with bipolar disorder (BPD); however, the emergence of impulse-control disorders has been documented in Parkinson's disease (PD) after pramipexole treatment. Performance on reward-based tasks is altered in healthy subjects after a single dose of pramipexole, but its potential to induce abnormalities in BPD patients is unknown. We assessed reward-dependent decision making in euthymic BPD patients pre- and post 8 weeks of treatment with pramipexole or placebo by using the Iowa Gambling Task (IGT). The IGT requires subjects to choose among four card decks (two risky and two conservative) and is designed to promote learning to make advantageous (conservative) choices over time. Thirty-four BPD patients completed both assessments (18 placebo and 16 pramipexole). Baseline performance did not differ by treatment group (F=0.63; p=0.64); however, at week 8, BPD patients on pramipexole demonstrated a significantly greater tendency to make increasingly high-risk, high-reward choices across the five blocks, whereas the placebo group's pattern was similar to that reported in healthy individuals (treatment × time × block interaction, p<0.05). Analyses of choice strategy using the expectancy valence model revealed that after 8 weeks on pramipexole, BPD patients attended more readily to feedback related to gains than to losses, which could explain the impaired learning. There were no significant changes in mood symptoms over the 8 weeks, and no increased propensity toward manic-like behaviors were reported. Our results suggest that the enhancement of dopaminergic activity influences risk-associated decision-making performance in euthymic BPD. The clinical implications remain unknown.
我们最近报道称,D2/D3 激动剂普拉克索可能对双相情感障碍(BPD)的缓解期患者具有认知促进作用;然而,在帕金森病(PD)患者接受普拉克索治疗后,已记录到冲动控制障碍的出现。在健康受试者中,单次服用普拉克索后,基于奖励的任务表现会发生改变,但它在 BPD 患者中诱导异常的潜力尚不清楚。我们通过使用爱荷华赌博任务(IGT)来评估缓解期 BPD 患者在接受普拉克索或安慰剂治疗前 8 周和治疗 8 周后的奖励依赖性决策制定。IGT 要求受试者在四张牌组(两张冒险和两张保守)中进行选择,旨在促进随着时间的推移做出有利(保守)选择的学习。34 名 BPD 患者完成了两项评估(18 名安慰剂和 16 名普拉克索)。基线表现不因治疗组而异(F=0.63;p=0.64);然而,在第 8 周时,服用普拉克索的 BPD 患者在五个区块中表现出越来越倾向于做出高风险、高回报选择的显著趋势,而安慰剂组的模式与健康个体相似(治疗×时间×区块交互作用,p<0.05)。使用期望效价模型对选择策略进行分析表明,在服用普拉克索 8 周后,BPD 患者更容易关注与收益相关的反馈,而不是与损失相关的反馈,这可以解释学习受损的原因。在 8 周内,情绪症状没有明显变化,也没有报告出现躁狂样行为的倾向增加。我们的研究结果表明,多巴胺能活动的增强会影响缓解期 BPD 患者与风险相关的决策表现。其临床意义尚不清楚。