Neural and behavioral markers for motivational negative symptoms of schizophrenia: a longitudinal approach

精神分裂症动机阴性症状的神经和行为标记：纵向方法

• 批准号: 323528193
• 负责人: Professor Dr. Florian Schlagenhauf
• 金额: --
• 依托单位: Psychiatrische Universitätsklinik Zürich
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/323528193?language=en
• 关键词: Neural; behavioral; markers; motivational; negative

The motivational negative symptoms of schizophrenia include avolition, asociality and anhedonia. These symptoms strongly contribute to impairments in social and occupational functioning as well as quality of life. At the same time there is a lack of evidence-based biological and psychosocial treatment approaches. Recent research employing behavioral experiments and functional neuroimaging has linked negative symptoms mainly to dysfunctions of the reward system. Despite these advances, treatment development is still hindered by a lack of biomarkers that can reliably link clinical symptoms to pathophysiological mechanisms. This project will define a set of neural and behavioral markers that can serve as biomarkers for treatment development for motivational negative symptoms. For this purpose we will establish (1) that these markers are robustly associated with negative symptoms, (2) that this association is longitudinally stable and (3) that this association is stable across centers. Furthermore, we will assess the longitudinal predictive power of each neurobehavioral marker for motivational negative symptoms. Finally, we will explore whether a combination of markers can improve cross-sectional and longitudinal prediction and be useful for defining mechanistically informed patient subgroups.In a longitudinal study at two centers (Berlin and Zurich) we will recruit 132 patients with 66 patients with schizophrenia and 30 controls. These participants will have a full assessment of psychopathology, behavioral measures and functional magnetic resonance imaging at intake and at 3 months. In addition, a follow-up psychopathological assessment will be performed in patients 9 months after intake. Behavioral markers will be derived from tasks assessing reinforcement learning, effort-based decision making, goal-directed behavioral control and option generation. Functional magnetic resonance imaging markers will be obtained with tasks assessing reward anticipation, reinforcement learning and working memory. Analytic approaches will include state-of-the-art computational modeling of behavioral and imaging data using a reinforcement learning framework and dynamic causal modelling as well as unsupervised classification approaches.Establishing a stable set of neural and behavioral markers will improve our understanding of motivational negative symptoms by bridging clinical phenomena and pathophysiological mechanisms. These markers can contribute to treatment development by identifying potential targets for biological and psychosocial interventions and they can be used as endpoints in clinical trials to better define the mechanisms of treatment interventions. Overall, we believe that this project is of high importance, because it will allow transforming the promising results of recent behavioral and neuroimaging research into a set of markers that will considerably improve the foundation for treatment research on the negative symptoms of schizophrenia.

精神分裂症的动机阴性症状包括无意志、社交障碍和快感缺乏。这些症状严重影响社会和职业功能以及生活质量。与此同时，缺乏循证的生物和心理社会治疗方法。最近的研究采用行为实验和功能性神经影像学的负性症状，主要是奖励系统的功能障碍。尽管取得了这些进展，但由于缺乏能够可靠地将临床症状与病理生理机制联系起来的生物标志物，治疗开发仍然受到阻碍。该项目将定义一组神经和行为标志物，可以作为动机性阴性症状治疗开发的生物标志物。为此，我们将确定（1）这些标志物与阴性症状密切相关，（2）这种相关性是纵向稳定的，（3）这种相关性在各中心之间是稳定的。此外，我们将评估每个神经行为标记物对动机阴性症状的纵向预测能力。最后，我们将探讨是否结合标志物可以提高横截面和纵向预测和有用的定义机械告知患者subgroup.In纵向研究在两个中心（柏林和苏黎世），我们将招募132例患者，66例精神分裂症和30个控制。这些参与者将在摄入时和3个月时对精神病理学、行为测量和功能性磁共振成像进行全面评估。此外，将在摄入后9个月对患者进行随访精神病理学评估。行为标记将来自评估强化学习，基于努力的决策，目标导向的行为控制和选项生成的任务。功能性磁共振成像标记物将通过评估奖励预期、强化学习和工作记忆的任务获得。分析方法将包括使用强化学习框架和动态因果建模以及无监督分类方法对行为和成像数据进行最先进的计算建模。建立一套稳定的神经和行为标记物将通过桥接临床现象和病理生理机制来提高我们对动机性阴性症状的理解。这些标志物可以通过识别生物和心理干预的潜在目标来促进治疗开发，并且它们可以用作临床试验的终点，以更好地定义治疗干预的机制。总的来说，我们相信这个项目是非常重要的，因为它将允许转换最近的行为和神经影像学研究的有希望的结果，将大大改善精神分裂症阴性症状的治疗研究的基础的一组标记。