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

摘要 精神分裂症(SZ)的特征是严重的、令人衰弱的社会功能丧失。尽管 尽管作出了相当大的努力来寻找改善社会职能的方法，但几乎没有取得令人满意的进展。这个 SZ的典型发病年龄(即青春期晚期/成年期早期)与关键时期不谋而合 心理社会发展，在此期间，个人学习形成和维持关系、服务于 作为整个成年期成功社交的基础。在此期间，动态变化 同样发生在大脑中，这可能会对社会功能产生终生影响。一项纵向研究 病程早期的个体将为了解这一关键的发育阶段提供一个窗口，从而 美国将研究影响深圳社会功能的潜在机制。我们最近提出了一种理论 扰乱社会偏好和谷氨酸N-甲基-D-天冬氨酸受体的模型 功能减退是了解深圳社会功能障碍的关键。社会偏好指的是偏见或 个体倾向于优先处理社会性刺激而不是非社会性刺激。此模型基于 来自发育科学、临床科学和行为神经科学的融合证据。本R01 旨在使用纵向多模式神经成像方法对上述模型进行评估，该方法应用于70例 两名首发SZ患者和72名人口统计学上匹配的对照组。我们会招募病人 在他们被加州大学洛杉矶分校的善后护理研究计划录取后，他们将获得 强化社会心理干预，包括社会认知训练，为期6个月，作为后续护理的一部分 程序。患者将在基线和6个月时进行评估；对照组仅在基线时进行评估。 使用功能磁共振成像(FMRI)，我们将通过对比社会功能来测量神经激活 而不是社会偏好任务中的非社会奖励。使用质子磁共振波谱(1H MRS)，我们将获得谷氨酸能活动指数(即谷氨酸水平)。主要感兴趣的区域 对于fMRI和1HMRS，将是腹侧纹状体和腹内侧额前皮质。社会认知和 还将对社会功能进行评估。通过这个设计，我们将确定1)首发患者 显示异常神经激活和谷氨酸水平2)神经激活和谷氨酸水平的纵向变化 谷氨酸水平与患者接受综合治疗后社会认知能力的变化有关 第一集之后的治疗。作为探索性目标，使用集成fMRI的多模式方法，1H MRS和行为评估数据，我们将测试扰乱的社会偏好、谷氨酸 患者病程早期的水平和社会功能。这个项目的发现可能 在社会功能障碍和精神分裂症的病理生理过程之间提供了亟需的联系 以及针对社会功能障碍的潜在治疗药物的方向建议 谷氨酸能系统。

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.