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

精神分裂症高危精神状态患者的元认知缺陷及其与精神病理学、认知功能障碍和功能成像的相互作用

• 批准号: 192623319
• 负责人: Professor Dr. Peter Kirsch
• 金额: --
• 依托单位: Klinik für Psychiatrie und Psychotherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/192623319?language=en
• 关键词: Metacognitive; deficits; patients; risk; mental

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.

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观念有关。到目前为止，尚不清楚元认知缺陷是否先于精神病发作，并且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功能改变的关系也尚未得到充分了解。我们申请对 ARMS 患者进行一项全面的调查，涉及敏感功能磁共振成像 (fMRI) 任务中的元认知、神经心理学表现和神经元激活。根据 DFG 评审员对此申请 (ZI1253/3-1) 的建议，我们在原理证明研究中验证了该研究计划。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受试者样本。我们新开发的功能磁共振成像范式跳跃结论（JTC）揭示了在对整个任务进行块设计分析时，整个样本中预期的广泛皮质激活模式。在分析事件相关方法的最终决策时，我们观察到伏隔核（NACC）和腹侧被盖区（VTA）的特定激活。有趣的是，精神分裂症患者在激活这些多巴胺能大脑区域方面表现出明显的缺陷。通过额外的功能磁共振成像任务以及综合神经心理学 (MATRICS) 和元认知测试对亚组进行了研究。在这里，我们检测到所有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，这项更新提案旨在调查 ARMS 患者精神病的早期发病机制。对于这项任务，我们能够联系并招募根据 CAARMS（危险心理状态综合评估）和 ERIraos（基于 IRAOS 的早期识别清单）工具定义的 63 名 ARMS 患者。这些患者在我们致力于早期发现和治疗精神病的特定门诊服务中得到了表征：FAPS（Head MZ）。此外，我们还建立了 192 名对照受试者的数据库。计划研究的主要终点将是 JTC-fMRI 范式中 NACC 和 VTA 激活的横断面比较。次要终点将是行为神经心理学和元认知领域的比较，以及其他功能磁共振成像范式（心理理论、金钱奖励预期、工作记忆）。 12 个月和 24 个月后的后续调查旨在调查这些参数之间的相互作用以及它们与一般病程（例如向精神病的转变）的相互作用。该项目将增进对精神分裂症认知和神经生物学发病机制的了解，并可能为创新治疗干预措施提供新目标。

项目成果

Neurocognitive capabilities modulate the integration of evidence in schizophrenia

• DOI: 10.1016/j.psychres.2014.04.056
• 发表时间: 2014-09-30
• 期刊: PSYCHIATRY RESEARCH
• 影响因子: 11.3
• 作者: Eifler, Sarah;Rausch, Franziska;Zink, Mathias
• 通讯作者: Zink, Mathias

Investigation of metamemory functioning in the at-risk mental state for psychosis

• DOI: 10.1017/s0033291715001373
• 发表时间: 2015-11-01
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Eisenacher, S.;Rausch, F.;Zink, M.
• 通讯作者: Zink, M.

Metamemory in schizophrenia: Retrospective confidence ratings interact with neurocognitive deficits

• DOI: 10.1016/j.psychres.2014.11.040
• 发表时间: 2015-02-01
• 期刊: PSYCHIATRY RESEARCH
• 影响因子: 11.3
• 作者: Eifler, Sarah;Rausch, Franziska;Zink, Mathias
• 通讯作者: Zink, Mathias

Evaluation of the ‘Jumping to conclusions’ bias in different subgroups of the at-risk mental state: from cognitive basic symptoms to UHR criteria

高危心理状态不同亚组的“跳出结论”偏差评估：从认知基本症状到UHR标准

• DOI: 10.1017/s0033291716000465
• 发表时间: 2016
• 期刊: Psychological Medicine
• 影响因子: 6.9
• 作者: Franziska Rausch;Sarah Eisenacher;Hasan Elkin;Susanne Englisch;Sarah Kayser;Nadine Striepens;Marion Lautenschlager;Andreas Heinz;Yehonala Gudlowski;Birgit Janssen;Wolfgang Gaebel;Tanja Maria Michel;Frank Schneider;Martin Lambert;Dieter Naber
• 通讯作者: Dieter Naber

Aberrant activity and connectivity of the posterior superior temporal sulcus during social cognition in schizophrenia

• DOI: 10.1007/s00406-016-0737-y
• 发表时间: 2017-10
• 期刊: European Archives of Psychiatry and Clinical Neuroscience
• 影响因子: 4.7
• 作者: D. Mier;S. Eisenacher;F. Rausch;S. Englisch;M. Gerchen;V. Zamoscik;A. Meyer-Lindenberg;M. Zink;P. Kirsch