Behavioral screening tools for identifying autism in macaques: existing and promising tests

Autism is a behaviorally defined neurodevelopmental disease characterized by social communication and social interaction deficits, as well as repetitive behaviors and restricted interests. Although the causes of autism are extremely complex, involving genes, environments and gene-environment interactions, genetic mutations are the important risk factors. For this reason, preclinical research is now shifting into focusing on generating transgenic and knockout models, especially using macaques, which are the closest relatives to humans. In spite of unique advantages of macaques over rodents in both functionally specialized brain structures and highly sophisticated social behaviors, the limited availability of phenotype screening tools restricts their translational utility. Here, this review focuses specially on behavioral phenotyping assays for macaque models of autism. In the first part, the existing behavioral tests are discussed, and the second part is devoted to some few, in our view, very promising tests of new developments. In years to come, we should develop macaque models with high construct validity, improve face validity by designing more specialized behavioral screening tools, strengthen collaborative efforts between rodent and macaque models, and ultimately translate the results from animal models into human clinical trials.