Metacognitive deficits in patients with at risk mental states for schizophrenia and their interaction with psychopathology, cognitive dysfunction and functional imaging

精神分裂症患者患有认知缺陷，特别是在监测和控制自己的思想方面表现出功能障碍。这些所谓的元认知偏差与妄想意念有关。到目前为止，尚不清楚元认知缺陷是否先于精神病发作，并可能存在于危险精神状态（ARMS）中。与其他认知功能障碍和相关的功能改变的关系也没有得到充分的理解。我们申请了一个全面的调查ARMS患者的元认知，神经心理性能和神经元激活敏感的功能性磁共振成像（fMRI）任务。根据DFG评审员对本申请（ZI 1253/3-1）的建议，我们在原理证明研究中验证了本研究项目。我们招募了24名精神分裂症患者和28名年龄、性别和教育程度相匹配的对照组。我们新开发的fMRI范式跳跃到结论（JTC）揭示了预期的广泛的皮质激活模式，在整个样本时，应用整个任务的块设计分析。当用事件相关方法分析最终决策时，我们观察到丘脑腹侧被盖区（VTA）和中脑背外侧核（NACC）的特异性激活。有趣的是，精神分裂症患者在激活这些多巴胺能脑区方面表现出明显的缺陷。亚组进行了额外的功能磁共振成像任务，以及全面的神经心理（MATRICS）和元认知测试。在这里，我们发现在所有的神经心理学和几个元认知领域的显着缺陷。在成功完成原理研究证明后，这项更新建议旨在调查ARMS患者精神病的早期发病机制。对于这项任务，我们能够联系和招募63名ARMS患者，根据CAARMS（风险心理状态综合评估）和ERGOS（基于IRAOS的早期识别量表）定义。这些患者在我们专门用于早期发现和治疗精神病的特定门诊服务中进行了表征：FAPS（MZ负责人）。此外，我们建立了一个数据库的192名对照组。计划研究的主要终点将是JTC-fMRI范例中NACC和VTA激活的横截面比较。次要终点将是行为神经心理学和元认知领域的比较，以及其他fMRI范式（心理理论、金钱奖励预期、工作记忆）。12个月和24个月后的随访调查旨在调查这些参数之间的相互作用以及与疾病的一般过程（例如转变为精神病）的相互作用。该项目将促进对精神分裂症的认知和神经生物学发病机制的认识，并可能为创新治疗干预提供新的目标。

Schizophrenia patients suffer from cognitive deficits and specifically show dysfunctions in monitoring and controlling their own thoughts. These so called metacognitive biases are associated with delusional ideation. So far, it is unclear whether deficits in metacognition precede the onset of psychosis and might be present in at risk mental states (ARMS). The relation to other cognitive dysfunctions and the associated functional alterations are also insufficiently understood. We applied for a comprehensive investigation of ARMS-patients regarding metacognition, neuropsychological performance and neuronal activation in sensitive functional magnetic resonance imaging (fMRI) tasks. In accordance with the recommendations of the DFG-reviewers to this application (ZI1253/3-1), we validated this investigational programme in a proof of principle study. We recruited samples of 24 schizophrenia patients and 28 control subjects matched for age, sex and education. Our newly developed fMRI-paradigm jumping to conclusion (JTC) revealed the expected broad cortical activation pattern in the whole sample when applying a block design analysis of the entire task. When analysing the final decision in an event related approach, we observed specific activations in nucleus accumbens (NACC) and ventral tegmental area (VTA). Interestingly, schizophrenia patients showed a significant deficit in activating these dopaminergic brain regions. Subgroups were investigated with additional fMRI tasks as well as comprehensive neuropsychological (MATRICS) and metacognitive testing. Here, we detected significant deficits in all neuropsychological and several metacognitive domains. After successfully completing the proof of principle study, this renewal proposal aims at investigating the early pathogenesis of psychosis in ARMS patients. For this task, we are able to contact and recruit 63 ARMS patients defined according to the instruments CAARMS (Comprehensive Assessment of At Risk Mental States) and ERIraos (Early Recognition Inventory based on IRAOS). These patients have been characterised in our specific outpatient service dedicated to the early detection and treatment of psychosis: FAPS (Head MZ). In addition, we established a data base of 192 control subjects. The primary endpoint of the planned study will be the cross-sectional comparison of the NACC- and VTA-activation in the JTC-fMRI paradigm. Secondary endpoints will be comparisons of behavioural neuropsychological and metacognitive domains, as well as additional fMRI-paradigms (theory of mind, monetary reward anticipation, working memory). Follow-up-investigations after 12 and 24 months aim at investigating the interactions of these parameters with each other and with the general course of illness (e.g. transition to psychosis). This project will foster the knowledge on the cognitive and neurobiological pathogenesis of schizophrenia and might provide new targets for innovative treatment interventions.