The utilization of non-human primates in the investigation of autism spectrum disorder

Abstract

Autism spectrum disorder (ASD), a prevalent neurodevelopmental condition characterized by social communication deficits and repetitive behaviors, presents significant therapeutic challenges due to its multifactorial etiology, clinical heterogeneity, and frequent comorbidities. To address these complexities, animal models have become indispensable tools for unraveling ASD pathogenesis and evaluating potential interventions. This review synthesizes recent advances across three pivotal research domains—neuroimaging biomarkers, metabolic dysregulation, and etiological mechanisms—while providing a critical evaluation of animal models, including rodent and non-human primate (NHP) paradigms developed through pharmacological induction, spontaneous mutations, and CRISPR-based gene editing. Although rodent models have substantially advanced our understanding of ASD-linked genetic pathways and neural circuitry, their limited capacity to model higher-order social cognition underscores the need for evolutionarily proximate systems. Non-human primates (NHPs), with their neuroanatomical homology to humans and complex socio-cognitive behaviors, offer unparalleled advantages for recapitulating core ASD phenotypes. Current evidence demonstrates that NHP models faithfully replicate hallmark behavioral manifestations while elucidating aberrant neural network dynamics and synaptic plasticity underlying these traits. Key challenges in the field include standardizing model validation protocols, addressing sex-specific phenotypic variability, and integrating multi-omics approaches for biomarker discovery and circuit-level analysis, and evaluating the translational utility of NHP models.