Brain-Behavior Mechanisms of Social Cognition in First-Episode Psychosis

首发精神病社会认知的脑行为机制

• 批准号: 10740563
• 负责人: Aubrey M. Moe
• 金额: $ 19.2万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740563
• 关键词: Activities of Daily Living; Address; Area; Behavior; Behavioral; Behavioral Mechanisms; Belief; Brain; Brain region; Clinical; Clinical Research; Cognition; Cognitive; Cognitive remediation; Coupled; Data; Data Collection; Development; Devices; Diagnostic; Early Intervention; Ecological momentary assessment; Effectiveness; Enrollment; Exhibits; Feeling suicidal; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Health Technology; Illness impact; Impaired cognition; Impairment; Individual; Intervention; Intervention Studies; Investigation; Knowledge; Laboratories; Link; Measures; Medial; Mental Processes; Mentors; Mind; Nature; Neurobiology; Neurocognition; Neurophysiology - biologic function; Occupational; Outcome; Outcome Measure; Participant; Performance; Persons; Phase; Prefrontal Cortex; Psychoses; Psychotic Disorders; Sampling; Social Behavior; Social Functioning; Social Interaction; Social Processes; Social outcome; Source; Stimulus; Time; Training; Translations; animation; base; behavioral construct; biobehavior; brain based; brain behavior; career; clinically relevant; cognitive function; cognitive neuroscience; cognitive performance; cognitive process; cognitive task; daily functioning; early psychosis; experience; first episode psychosis; functional disability; functional outcomes; improved; indexing; innovation; mHealth; mental state; mentalization; multimodality; network dysfunction; neural; neuromechanism; novel therapeutics; outcome prediction; performance based measurement; psychiatric symptom; psychosocial; recruit; response; skills; social; social cognition; social deficits; social influence; social neuroscience; stress reactivity; theories; translational neuroscience; young adult

PROJECT SUMMARY Psychotic disorders are serious illnesses that lead to significant functional impairment, even during the early course of illness (i.e., first-episode psychosis; FEP). Social cognition is a strong predictor of key functional outcomes in psychosis (i.e., social and occupational functioning) and among social cognitive domains, mentalizing – the ability to infer and reason about the mental states of other people – is most robustly impaired and simultaneously most predictive of outcomes. However, existing interventions addressing social cognitive dysfunction in psychosis are minimally effective in improving real-world outcomes. Further, though psychosis studies have revealed abnormal function in brain areas comprising the mentalizing network (MN; e.g., medial prefrontal cortex and temporoparietal junction), the vast majority of existing studies have utilized fMRI paradigms that use non-human or non-interactive stimuli that may limit ecological validity and further fail to examine associations between neural function and real-world outcomes. Collectively, social cognition is a critical factor in psychosis that remains poorly understood. Thus, the proposed study will combine neural, behavioral, and real- world functioning measures to delineate brain-behavior mechanisms of social cognition in FEP. The study will enroll 45 FEP individuals and 45 matched non-clinical controls (NCC) and assess their neural (i.e., fMRI) and behavioral (i.e., validated laboratory-based measures) social cognitive function as well as their real-world social and occupational behavior. Data from this study will allow for an innovative investigation of whether MN dysfunction is associated with social cognitive performance on validated behavioral tasks both across and within FEP and NCC participants (Aim 1), and how these brain-behavior measures of social cognitive performance relate to laboratory-based measures of social and occupational functioning (Aim 2). The current study will also examine the extent to which MN function predicts real-world social and occupational functioning assessed via ecological momentary assessment (Aim 3). This proposal concurrently provides an excellent opportunity to receive mentor-directed, hands-on training in several key areas necessary to refine the candidate’s knowledge and skill-sets. Though the candidate has extensive clinical research experience in FEP and has completed foundational fMRI training, she proposes a training plan focused on three new domains: 1) advanced social- cognitive neuroscience and fMRI task development, 2), linking of fMRI to behavioral constructs of social cognition and functional outcome, and 3) translation of fMRI and behavioral constructs to psychosis. The proposed study coupled with completion of the training plan will effectively launch the candidate toward her long-term goal of an independent career in the translational neuroscience of social-cognitive dysfunction in early psychosis, and will lay the foundation for future, high-impact R01 studies focused on refined identification and targeting of biobehavioral factors influencing social and functional outcomes.

项目总结 精神障碍是一种严重的疾病，即使在早期也会导致严重的功能障碍 病程(即首发精神病；FEP)。社会认知是关键功能的有力预测者 精神病(即社会和职业功能)和社会认知领域的结果， 精神化--对他人的心理状态进行推断和推理的能力--受到的损害最大 同时也是最具预测性的结果。然而，针对社会认知的现有干预措施 精神病的功能障碍在改善现实世界的结果方面效果微乎其微。更进一步，尽管精神病 研究表明，组成心智网络(MN；例如，内侧)的大脑区域功能异常 前额叶皮质和颞顶交界处)，现有的绝大多数研究都利用了功能磁共振成像范式 使用非人类或非交互刺激，可能会限制生态有效性，并进一步无法检查 神经功能和现实世界结果之间的联系。总的来说，社会认知是一个关键因素 至今仍知之甚少的精神病。因此，这项拟议的研究将结合神经、行为和现实- 描述FEP中社会认知的大脑行为机制的世界功能测量。这项研究将 招募45名FEP患者和45名匹配的非临床对照(NCC)，并评估他们的神经(即fMRI)和 行为(即，经过验证的基于实验室的测量)社会认知功能及其现实社会 和职业行为。这项研究的数据将允许对MN是否有创新的调查 功能障碍与在有效行为任务中的社会认知表现有关 FEP和NCC参与者(目标1)，以及这些大脑行为如何衡量社会认知表现 涉及以实验室为基础的社会和职业功能测量(目标2)。目前的研究还将 检查MN功能预测现实世界的社会和职业功能的程度，通过 生态瞬时评估(目标3)。这项提议同时提供了一个极好的机会 在几个关键领域接受导师指导的实践培训，以完善候选人的知识 和一整套技能。尽管应聘者在FEP方面有丰富的临床研究经验，并已完成 作为基础功能磁共振成像培训，她提出了一个专注于三个新领域的培训计划：1)高级社交- 认知神经科学和功能磁共振任务开发，2)功能磁共振与社会认知的行为结构的联系 和功能结果，以及3)将功能磁共振成像和行为结构转换为精神病。建议进行的研究 再加上培训计划的完成，将有效地推动候选人朝着她的长期目标 独立从事早期精神病社会认知功能障碍的翻译神经科学研究，并将 为未来高影响力的R01研究奠定基础，重点是精细化识别和确定目标 影响社会和功能结果的生物行为因素。