BACKGROUND Impaired probabilistic reasoning and the jumping-to-conclusions reasoning bias are hallmark features of schizophrenia (SCZ), yet the neuropharmacological basis of these deficits remains unclear. Here we tested the hypothesis that glutamatergic neurotransmission specifically contributes to jumping to conclusions and impaired probabilistic reasoning in SCZ. METHODS A total of 192 healthy participants received either NMDA receptor agonists/antagonists (D-cycloserine/dextromethorphan), dopamine type 2 receptor agonists/antagonists (bromocriptine/haloperidol), or placebo in a randomized, double-blind, between-subjects design. In addition, we tested 32 healthy control participants matched to 32 psychotic inpatients with SCZ-a state associated with compromised probabilistic reasoning due to reduced glutamatergic neurotransmission. All experiments employed two versions of a probabilistic reasoning (beads) task, which required participants to either sample individual amounts of sensory information to infer correct decisions or provide explicit probability estimates for presented sensory information. Our task instantiations assessed both information sampling and explicit probability estimates in different probabilistic contexts (easy vs. difficult conditions) and changing sensory information through random transitions among easy, difficult, and ambiguous trial types. RESULTS Following administration of D-cycloserine, haloperidol, and bromocriptine, healthy participants displayed data-gathering behavior that was normal compared with placebo and was adequate in the context of all employed task conditions and trial level difficulties. However, healthy participants receiving dextromethorphan displayed a jumping-to-conclusions bias, abnormally increased probability estimates, and overweighting of sensory information. These effects were mirrored in patients with SCZ performing the same versions of the beads task. CONCLUSIONS Our findings provide novel neuropharmacological evidence linking reduced glutamatergic neurotransmission to impaired information sampling and to disrupted probabilistic reasoning, namely to overweighting of sensory evidence, in patients with SCZ.

中文翻译：

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谷氨酸对精神分裂症概率推理和得出结论的贡献：一项双盲随机实验试验。

背景 受损的概率推理和直接得出结论的推理偏差是精神分裂症 (SCZ) 的标志性特征，但这些缺陷的神经药理学基础仍不清楚。在这里，我们测试了谷氨酸能神经传递特别有助于在 SCZ 中得出结论和受损概率推理的假设。方法 共有 192 名健康参与者在随机、双盲、受试者间设计中接受了 NMDA 受体激动剂/拮抗剂（D-环丝氨酸/右美沙芬）、多巴胺 2 型受体激动剂/拮抗剂（溴隐亭/氟哌啶醇）或安慰剂。此外，我们测试了与 32 名患有 SCZ 的精神病住院患者相匹配的 32 名健康对照参与者 - 一种由于谷氨酸能神经传递减少而导致概率推理受损的状态。所有实验都采用了概率推理（珠子）任务的两个版本，该任务要求参与者对单独数量的感官信息进行采样以推断正确的决定，或者为所呈现的感官信息提供明确的概率估计。我们的任务实例评估了不同概率上下文（简单与困难条件）下的信息采样和显式概率估计，并通过简单、困难和模糊试验类型之间的随机转换来改变感官信息。结果 服用 D-环丝氨酸、氟哌啶醇和溴隐亭后，健康参与者表现出的数据收集行为与安慰剂相比是正常的，并且在所有就业任务条件和试验级别困难的情况下都足够。然而，接受右美沙芬的健康参与者表现出跳到结论的偏见，概率估计异常增加，以及感官信息的过度重视。这些效果在执行相同版本的珠子任务的 SCZ 患者身上得到了反映。结论我们的研究结果提供了新的神经药理学证据，将减少的谷氨酸能神经传递与受损的信息采样和破坏的概率推理联系起来，即过度重视 SCZ 患者的感觉证据。