Towards an Endophenotype for Amygdala Dysfunction

描述（由申请人提供）：在过去的十年中，我们的实验室和其他实验室的研究已经证实了杏仁核在社会感知中的重要参与，例如处理面孔，并产生了关于它在精神疾病（如自闭症）中的作用的假设。然而，杏仁核在调节社会功能障碍的内表型中可能发挥的确切作用仍然知之甚少。本次修订的申请计划在三个具体目标下对该主题进行系统而深入的研究。目标1将调查真实社会互动（通过实时视频和面对面互动）中的眼球运动和情绪反应。这将量化杏仁核对现实社会互动的贡献，以及自闭症引起的损害。目的2将更详细地研究包含人脸的社交场景的处理，并梳理出由于缺乏对人脸的吸引力而可能产生的厌恶。目标3将使用“气泡”方法来研究面部的哪些特征在行为、情感和神经层面上驱动歧视。这些实验将辅以详细的问卷调查和访谈，以评估现实生活中的社会功能，并探索个体差异。研究对象包括扁桃体局灶性损伤的神经学研究对象、患有自闭症的高功能研究对象、具有广泛自闭症表型的自闭症儿童的父母以及典型的神经控制组。这两组之间的对比将检验一个整体假设，即杏仁核功能障碍会导致自闭症患者以及自闭症患者的一级亲属出现社交障碍。杏仁核功能受损的内表型可能导致几种被认为是杏仁核功能失调的精神疾病，包括抑郁症、焦虑症、精神分裂症和自闭症。这也可能导致健康人群在易患这些精神疾病方面的个体差异，特别是在那些与这些疾病有大量遗传变异的人（如一级亲属）中。我们的刺激和方法将提供给研究精神疾病的研究人员和临床医生，并将为诊断提供信息，并为设计未来的干预措施提供基础。

DESCRIPTION (provided by applicant): Studies from our laboratory as well as others over the past decade have confirmed the important participation of the amygdala in social perception, such as processing faces, and generated hypotheses about its role in mental illness, such as autism. Yet the precise role that the amygdala might play in mediating an endophenotype for social dysfunction remains poorly understood. This revised application plans a systematic and in-depth investigation of this topic in three specific aims. Aim 1 will investigate eye movements and emotional response during real social interactions (over live video and during face-to-face interactions). This will quantify the amygdala's contribution to realistic social interactions, and the impairments arising from autism. Aim 2 will investigate in more detail processing of social scenes containing faces, and tease apart possible aversion to faces from lack of attraction to them. Aim 3 will use the "bubbles" method to investigate which features in faces drive discrimination at the behavioral, emotional, and neural level. These experiments will be complemented by detailed questionnaires and interviews to assess real-life social functioning, and to explore individual differences. The aims will be carried out in neurological subjects with focal lesions of the amygdala, in high-functioning subjects with autism, in parents of autistic children who have the Broad Autism Phenotype, as well as in neurotypical controls. Contrasts between these groups will test the overall hypothesis that amygdala dysfunction contributes to the social impairments seen in autism as well as in first-degree relatives of people with autism. An endophenotype for impaired amygdala function is likely to contribute to several psychiatric illnesses in which the amygdala is thought to be dysfunctional, including depression, anxiety disorders, schizophrenia and autism. It is also likely to contribute to individual differences in the healthy population on dimensions that predispose to these psychiatric diseases, especially in those who share substantial genetic variance with these diseases (such as first-degree relatives). Our stimuli and methods will be made available to researchers and clinicians studying mental illness, and will inform diagnosis as well as provide a basis for designing future interventions.