Psychosis Research Unit, Aarhus University Hospital, 8200 Aarhus, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8200 Aarhus, Denmark.
Brain. 2021 Jun 22;144(5):1603-1614. doi: 10.1093/brain/awab065.
An abnormality in inference, resulting in distorted internal models of the world, has been argued to be a common mechanism underlying the heterogeneous psychopathology in schizophrenia. However, findings have been mixed as to wherein the abnormality lies and have typically failed to find convincing relations to symptoms. The limited and inconsistent findings may have been due to methodological limitations of the experimental design, such as conflating other factors (e.g. comprehension) with the inferential process of interest, and a failure to adequately assess and model the key aspects of the inferential process. Here, we investigated probabilistic inference based on multiple sources of information using a new digital version of the beads task, framed in a social context. Thirty-five patients with schizophrenia or schizoaffective disorder with a wide range of symptoms and 40 matched healthy control subjects performed the task, where they guessed the colour of the next marble drawn from a jar based on a sample from the jar as well as the choices and the expressed confidence of four people, each with their own independent sample (which was hidden from participant view). We relied on theoretically motivated computational models to assess which model best captured the inferential process and investigated whether it could serve as a mechanistic model for both psychotic and negative symptoms. We found that 'circular inference' best described the inference process, where patients over-weighed and overcounted direct experience and under-weighed information from others. Crucially, overcounting of direct experience was uniquely associated with most psychotic and negative symptoms. In addition, patients with worse social cognitive function had more difficulties using others' confidence to inform their choices. This difficulty was related to worse real-world functioning. The findings could not be easily ascribed to differences in working memory, executive function, intelligence or antipsychotic medication. These results suggest hallucinations, delusions and negative symptoms could stem from a common underlying abnormality in inference, where directly experienced information is assigned an unreasonable weight and taken into account multiple times. By this, even unreliable first-hand experiences may gain disproportionate significance. The effect could lead to false perceptions (hallucinations), false beliefs (delusions) and deviant social behaviour (e.g. loss of interest in others, bizarre and inappropriate behaviour). This may be particularly problematic for patients with social cognitive deficits, as they may fail to make use of corrective information from others, ultimately leading to worse social functioning.
推理异常导致对世界内部模型的扭曲，被认为是精神分裂症异质精神病学的共同机制。然而，关于异常所在的研究结果却存在分歧，并且通常未能找到与症状有说服力的关系。这些有限且不一致的发现可能是由于实验设计的方法学限制所致，例如将其他因素（例如理解）与感兴趣的推理过程混淆，以及未能充分评估和模拟推理过程的关键方面。在这里，我们使用一种新的珠子任务数字版本，在社会背景下，研究了基于多种信息源的概率推理。三十五名患有精神分裂症或分裂情感障碍的患者，其症状范围广泛，与四十名匹配的健康对照者一起完成了任务，他们根据从罐子中抽取的样本以及四个人的选择和表达的信心，猜测下一个抽取的大理石的颜色，每个人都有自己独立的样本（参与者无法看到）。我们依赖于理论驱动的计算模型来评估哪种模型最能捕捉推理过程，并研究它是否可以作为精神病性和阴性症状的机械模型。我们发现，“循环推理”最能描述推理过程，患者过度重视和重复计算直接经验，而低估他人的信息。至关重要的是，直接经验的重复计算与大多数精神病性和阴性症状都有独特的关联。此外，社会认知功能较差的患者在利用他人的信心来指导选择方面存在更大的困难。这种困难与现实世界中的功能较差有关。这些发现不能轻易归因于工作记忆、执行功能、智力或抗精神病药物的差异。这些结果表明，幻觉、妄想和阴性症状可能源于推理中的共同异常，其中直接体验到的信息被赋予不合理的权重并被多次考虑。通过这种方式，即使是不可靠的第一手经验也可能获得不成比例的重要性。这种影响可能导致错误的感知（幻觉）、错误的信念（妄想）和异常的社会行为（例如对他人失去兴趣、怪异和不适当的行为）。对于社会认知功能受损的患者来说，这可能是特别成问题的，因为他们可能无法利用他人的纠正信息，最终导致社会功能更差。
