Towards an Endophenotype for Amygdala Dysfunction

我们的实验室以及其他实验室在过去十年中的研究已经证实了 杏仁核在社会知觉中的作用，如处理面孔，并产生了关于其在社会知觉中的作用的假设。 精神疾病，如自闭症。然而，杏仁核可能在调节神经元的活动中发挥的确切作用， 社会功能障碍的内表型仍然知之甚少。这一修订后的应用计划， 并在三个具体目标下对这一课题进行了深入研究。目标1将研究眼球运动， 在真实的社交互动中的情绪反应（通过实时视频和在面对面的互动中）。这 将量化杏仁核对现实社会互动的贡献，以及 自闭症目标2将更详细地研究包含面孔的社会场景的处理， 对面孔缺乏吸引力而可能产生的厌恶。目标3将使用 气泡 法调查 面部的哪些特征在行为、情感和神经层面上驱动了歧视。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。这些目标将在具有局灶性病变的神经系统受试者中进行。 杏仁核，在自闭症高功能受试者中，在患有广泛自闭症的自闭症儿童的父母中 表型，以及在神经型对照。这些组之间的对比将检验总体假设 杏仁核功能障碍会导致自闭症和一级自闭症患者的社交障碍， 自闭症患者的亲属杏仁核功能受损的内在表型可能导致一些精神疾病， 杏仁核被认为是功能失调的，包括抑郁症，焦虑症，精神分裂症和 自闭症它还可能导致健康人群在以下维度上的个体差异， 易患这些精神疾病，特别是那些与这些疾病有大量遗传差异的人。 疾病（如一级亲属）。我们的刺激和方法将提供给研究人员， 研究精神疾病的临床医生，并将告知诊断，以及为设计未来的基础， 干预措施。

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.