Abstract Autism spectrum disorder (ASD) is a class of severe neurodevelopmental disorders with a high incidence in young children, and its pathogenesis remains elusive. There is no effective treatment, and ASD children usually have a hard time in integrating into society and leading a normal life, which places a heavy burden on the families and society. Studies have shown that in addition to genetic factors, environmental factors are another important risk contributing to the pathogenesis of ASD. Early environmental adversity, which can lead to abnormal brain development and affect cognition and behavior, greatly increases the incidence of a variety of brain developmental diseases including ASD. However, studies on this aspect are inadequate at present, and no clear conclusions can be drawn. We explored whether early adversity could trigger ASD core clinical symptoms in macaques by modeling early adversity through maternal separation. In this study, we conducted a rigorous behavioral analysis of 12 male macaques (1.5-2 years old) that underwent maternal separation and 9 male normal macaques of the same age that had been mother raised, and found that maternal separation could induce a small number of the young individuals to develop three core symptoms of ASD, including social impairment, stereotyped behaviors, and restricted interest simultaneously. According to DSM-V and ASD clinical diagnostic criteria, these individuals should be ASD macaques for having all the three core ASD symptoms at the same time., For the first time, this study reveals that early environmental adversity can lead to ASD pathogenesis in monkeys, and provides a new approach for future ASD studies and modeling ASD monkeys.

Maternal separation induces autism spectrum disorder in young rhesus monkeys