Disrupted eye gaze perception as a biobehavioral marker of social dysfunction: An RDoC investigation

项目概要/摘要 社交功能障碍是多种精神疾病中的一个棘手问题，损害了患者的 就业、独立生活和维持有意义的关系的能力。识别常见的 跨疾病社会障碍的标志并了解其机制是 开发可有效应用于诊断和疾病的有针对性的神经生物学治疗方法 改善功能结果的阶段。该项目的重点是眼睛的注视感知，以及准确地 并有效地区分他人的注视方向，作为社会功能的潜在生物标志物 精神科诊断。这个前提建立在显示凝视感知的猴子和人类文献之上 作为支持更高层次的社会沟通和社会发展的基本组成部分，以及 多种精神疾病中的凝视感知异常，伴有显着的社交功能障碍 （例如，精神病谱系障碍、自闭症谱系障碍、社交恐惧症）。大样本 (n= 225) 患有不同程度的青少年和青年（14-30 岁）精神病患者（无论诊断如何） 本研究将招募 75 名社会功能受损的健康对照者和人口统计学匹配的健康对照者。 参与者的精神表型、认知、社会认知和社区功能将 维度特征。眼睛注视感知将使用心理物理学任务进行评估，并且两个 分别利用视觉上的凝视感知干扰的指标（精度、自我参照偏差） 与一般缺陷无关的感知和解释水平将使用贝叶斯模型得出。 一部分参与者（150 名精神病患者，75 名健康对照者）将另外接受多模式治疗 功能磁共振成像确定改变注视感知的功能和结构大脑网络特征。具体的 该项目的目标有三个： 目标 1) 确定凝视感知干扰的普遍性 具有明显社交功能障碍的精神病患者； 2）绘制凝视感知的行为指数 精神表型和核心功能域的维度受到干扰； 3）识别神经 患有社会功能障碍的精神病患者凝视感知改变的相关性。顺利完成 这些具体目标将确定具体的基本缺陷、临床特征和潜在的神经回路 与社会功能障碍相关，可用于指导有针对性的个性化治疗，从而推进 NIMH 的战略目标 1（描述与精神疾病相关的神经回路并绘制 连接体治疗精神疾病）和目标 3（根据以下发现开发新的治疗方法） 神经科学和行为科学）。

Project Summary/Abstract Social dysfunction is an intractable problem in a wide spectrum of psychiatric illnesses, undermining patients’ capacities for employment, independent living, and maintaining meaningful relationships. Identifying common markers of social impairment across disorders and understanding their mechanisms are prerequisites to developing targeted neurobiological treatments that can be applied productively across diagnoses and illness stages to improve functional outcome. This project focuses on eye gaze perception, the ability to accurately and efficiently discriminate others’ gaze direction, as a potential biomarker of social functioning that cuts across psychiatric diagnoses. This premise builds on both the monkey and human literatures showing gaze perception as a basic building block supporting higher-level social communication and social development, and reports of abnormal gaze perception in multiple psychiatric conditions accompanied by prominent social dysfunction (e.g., psychosis-spectrum disorders, autism-spectrum disorders, social phobia). A large sample (n= 225) of adolescent and young adult (age 14-30) psychiatric patients (regardless of diagnosis) with various degrees of impaired social functioning, and 75 demographically matched healthy controls will be recruited for this study. Participant’s psychiatric phenotypes, cognition, social cognition, and community functioning will be dimensionally characterized. Eye gaze perception will be assessed using a psychophysical task, and two metrics (precision, self-referential bias) that respectively tap into gaze perception disturbances at the visual perceptual and interpretation levels, independent of general deficits, will be derived using Bayesian modeling. A subset of the participants (150 psychiatric patients, 75 healthy controls) will additionally undergo multimodal fMRI to determine the functional and structural brain network features of altered gaze perception. The specific aims of this project are three fold: Aim 1) Determine the generality of gaze perception disturbances in psychiatric patients with prominent social dysfunction; 2) Map behavioral indices of gaze perception disturbances to dimensions of psychiatric phenotypes and core functional domains; and 3) Identify the neural correlates of altered gaze perception in psychiatric patients with social dysfunction. Successfully completing these specific aims will identify the specific basic deficits, clinical profile, and underlying neural circuits associated with social dysfunction that can be used to guide targeted, personalized treatments, thus advancing NIMH’s Strategic Objective 1 (describe neural circuits associated with mental illnesses and map the connectomes for mental illnesses) and Objective 3 (develop new treatments based on discoveries in neuroscience and behavioral science).