Table_1_Reduced childhood social attention in autism model marmosets predicts impaired social skills and inflexible behavior in adulthood.XLSX

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social and communication impairments and restricted and repetitive behavior. Although there is currently no established cure for ASD, early interventions for deficits of attention to other individuals are expected to reduce the progression of ASD symptoms in later life. To confirm this hypothesis and improve early therapeutic interventions, it is desirable to develop an animal model of ASD in which social attention is impaired in childhood and ASD-like social behavior is observed in adulthood. However, rodent models of ASD have difficulty in recapitulating the deficit of gaze-based social attention. In this study, we examined the direction of gaze toward other conspecifics during childhood and puberty in a three-chamber test setting using an ASD marmoset model produced by maternal exposure to valproic acid (VPA). We also conducted a reversal learning test in adult VPA-exposed marmosets as an indicator of perseveration, a core symptom of ASD that has not previously been investigated in this model. The results showed that time spent gazing at other conspecifics was reduced in VPA-exposed marmosets in childhood, and that mature animals persisted with previous strategies that required long days for acquisition to pass the test. In a longitudinal study using the same animals, deficits in social attention in childhood correlated well with ASD-like social disturbance (inequity aversion and third-party reciprocity) and inflexible behavior in adulthood. Since VPA-exposed marmosets exhibit these diverse ASD-like behaviors that are consistent from childhood to adulthood, VPA-exposed marmosets will provide a valuable means of elucidating mechanisms for early intervention and contribute to the development of early therapies.

自闭症谱系障碍（Autism Spectrum Disorder, ASD）是一类以社交与沟通障碍、受限及重复行为为特征的神经发育疾病。目前尚无针对ASD的根治手段，但针对个体注意力缺陷的早期干预，有望延缓后续生命周期中ASD症状的进展。为验证这一假说并优化早期治疗干预方案，亟需构建一种在童年阶段存在社交注意力损伤、成年后表现出类ASD社交行为的动物模型。然而，现有啮齿类ASD模型难以复现基于凝视的社交注意力缺陷。本研究利用母体暴露于丙戊酸（Valproic Acid, VPA）构建的狨猴ASD模型，在三箱实验范式下，检测了幼年及青春期狨猴对同类个体的凝视方向偏好。此外，我们还对成年VPA暴露狨猴开展了反转学习测试，以此作为持续刻板行为的检测指标——这是ASD核心症状之一，此前尚未在该模型中得到研究。结果显示，幼年VPA暴露狨猴对同类的凝视时长显著减少；而成年动物则会持续依赖需要长期训练才能掌握的原有策略完成测试。在针对同一批动物的纵向研究中，童年时期的社交注意力缺陷，与成年后类ASD社交障碍（不公平厌恶及第三方互惠行为异常）及行为僵化表现出显著相关性。由于VPA暴露狨猴可呈现从童年至成年均稳定存在的多样化类ASD行为，该模型将为阐明早期干预机制提供宝贵的研究工具，并助力早期治疗方案的开发。