Disrupted Social Preference in Early Psychosis: A Longitudinal Multimodal Neuroimaging Study

早期精神病中社会偏好的破坏：一项纵向多模态神经影像学研究

• 批准号: 10160700
• 负责人: Junghee Lee
• 金额: $ 53.29万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10160700
• 关键词: Admission activity; Adult; Affect; Aftercare; Age of Onset; Behavior assessment; Behavioral; Brain; Clinical Sciences; Data; Development; Elements; Foundations; Functional Magnetic Resonance Imaging; Glutamates; Human; Impaired cognition; Individual; Intervention; Lead; Learning; Life; Link; Longitudinal Studies; Magnetic Resonance Spectroscopy; Measures; Mediating; Modeling; N-Methyl-D-Aspartate Receptors; N-methyl-D-glutamate; National Institute of Mental Health; Neurosciences; Patient Recruitments; Patients; Phase; Prefrontal Cortex; Process; Protons; Psychotic Disorders; Research; Rewards; Rodent; Role; Schizophrenia; Science; Social Functioning; Social Interaction; Stimulus; System; Testing; Theoretical model; Therapeutic Agents; Ventral Striatum; base; cognitive development; cognitive performance; cognitive training; critical period; design; early adolescence; emerging adult; first episode schizophrenia; improved; indexing; interest; multimodality; neuroimaging; preference; programs; psychosocial; psychosocial development; relating to nervous system; response; skills; social; social cognition; social deficits; theories

ABSTRACT Schizophrenia (SZ) is characterized by a severe and debilitating loss of social functioning. Despite considerable efforts to find ways to improve social functioning, little satisfactory progress has been made. The typical age of onset for SZ (i.e., late adolescence / early adulthood) coincides with a period of critical psychosocial development, during which individuals learn to form and maintain relationships, skills that serve as a foundation for successful social interactions throughout adulthood. During this period, dynamic changes also occur in the brain, which could have life-long effects on social functioning. A longitudinal study of individuals early in their course of illness will provide a window into this critical phase of development, allowing us to examine potential mechanisms affecting social functioning in SZ. We recently proposed a theoretical model in which disrupted social preference and glutamate N-methyl-D-aspartate receptor (NMDAR) hypofunction are crucial to understanding social dysfunction in SZ. Social preference refers to the bias or tendency for individuals to prioritize processing of social over nonsocial stimuli. This model is based on convergent evidence from developmental science, clinical science, and behavioral neuroscience. This R01 aims to evaluate the above model using a longitudinal multimodal neuroimaging approach applied to seventy- two patients with first-episode SZ and seventy-two demographically matched controls. We will recruit patients immediately after their admission into the UCLA Aftercare Research Program, in which they will receive an intensive psychosocial intervention, including social cognitive training, for 6 months, as part of the Aftercare Program. Patients will be assessed at both baseline and 6 months; controls will be assessed only at baseline. Using functional magnetic resonance imaging (fMRI), we will measure neural activation by contrasting social versus nonsocial reward during a social preference task. Using proton magnetic resonance spectroscopy (1H MRS), we will obtain an index of glutamatergic activity (i.e., glutamate levels). The primary regions of interest for both fMRI and 1H MRS will be the ventral striatum and ventromedial prefrontal cortex. Social cognition and social functioning will also be assessed. With this design, we will determine whether 1) first-episode patients show aberrant neural activation and glutamate levels 2) longitudinal changes in neural activations and glutamate levels are associated with changes in social cognitive performance as patients receive integrated treatments after their first episode. As an exploratory aim, using a multimodal approach integrating fMRI, 1H MRS and behavioral assessment data, we will test associations among disrupted social preference, glutamate levels, and social functioning in patients early in their courses of illness. The findings of this project could provide a much-needed link between social dysfunction and the pathophysiological processes of schizophrenia as well as suggesting directions for potential therapeutic agents for social dysfunction that target the glutamatergic system.

抽象的 精神分裂症（SZ）的特点是严重且令人衰弱的社会功能丧失。尽管 为寻找改善社会功能的方法付出了巨大努力，但几乎没有取得令人满意的进展。这 SZ 的典型发病年龄（即青春期晚期/成年早期）与关键时期一致 心理社会发展，在此期间个人学习建立和维持关系以及服务的技能 作为整个成年期成功社交互动的基础。在此期间，动态变化 也发生在大脑中，这可能对社会功能产生终生影响。纵向研究 处于病程早期的个体将为进入这一关键的发展阶段提供一个窗口，从而使 我们研究影响深圳社会功能的潜在机制。我们最近提出了一个理论 扰乱社会偏好和谷氨酸 N-甲基-D-天冬氨酸受体 (NMDAR) 的模型 功能减退对于理解深圳的社会功能障碍至关重要。社会偏好是指偏见或 个人倾向于优先处理社会刺激而不是非社会刺激。该模型基于 来自发育科学、临床科学和行为神经科学的聚合证据。这个R01 旨在使用应用于七十个的纵向多模态神经影像方法来评估上述模型 两名首发 SZ 患者和 72 名人口统计学匹配的对照患者。我们将招募患者 在他们进入加州大学洛杉矶分校善后研究计划后，他们将立即获得一份 作为善后护理的一部分，强化社会心理干预，包括为期 6 个月的社会认知训练 程序。患者将在基线和 6 个月时接受评估；仅在基线时评估控制措施。 使用功能磁共振成像 (fMRI)，我们将通过对比社交活动来测量神经激活 与社会偏好任务期间的非社会奖励相比。使用质子磁共振波谱（1H MRS），我们将获得谷氨酸活性指数（即谷氨酸水平）。主要感兴趣区域 对于 fMRI 和 1H MRS 来说，都是腹侧纹状体和腹内侧前额皮质。社会认知和 社会功能也将受到评估。通过这种设计，我们将确定是否 1) 首发患者 显示异常的神经激活和谷氨酸水平 2) 神经激活的纵向变化和 当患者接受整合治疗时，谷氨酸水平与社会认知表现的变化相关 第一次发作后的治疗。作为探索性目标，使用集成 fMRI、1H 的多模态方法 MRS 和行为评估数据，我们将测试扰乱的社会偏好、谷氨酸之间的关联 水平和患者病程早期的社会功能。该项目的研究结果可以 提供社会功能障碍和精神分裂症病理生理过程之间急需的联系 以及针对针对社会功能障碍的潜在治疗药物的方向提出建议 谷氨酸能系统。