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

This review looks at how scientists use animals, especially monkeys, to study autism. Mice have helped researchers understand autism genes and brain circuits, but they can't show the complex social behaviors seen in autism. Monkeys are better for autism research because their brains are more similar to humans and they have complex social behaviors like people do. The research shows that monkey models can copy the main autism behaviors and help scientists understand what goes wrong in the brain.

This review examines animal models used in autism spectrum disorder research, with particular focus on non-human primates (NHPs). While rodent models have advanced understanding of ASD genetics and neural pathways, they have limited capacity to model complex social cognition. NHP models offer advantages due to their neuroanatomical similarity to humans and complex social behaviors, demonstrating ability to replicate core ASD behavioral features while revealing underlying neural network abnormalities and synaptic dysfunction. The review covers three key research areas: neuroimaging biomarkers, metabolic dysregulation, and etiological mechanisms.

Current challenges include standardizing validation protocols, addressing sex-specific differences, and integrating multi-omics approaches for biomarker discovery and translational applications.

NHP models represent promising tools for ASD research that could improve translation to human applications. Their ability to model complex social behaviors and reveal neural mechanisms may accelerate development of targeted interventions. However, standardization of protocols and validation methods is needed before clinical translation.

As a review paper, findings depend on quality of underlying studies. Key challenges noted include lack of standardized validation protocols, sex-specific variability not fully addressed, and need for better integration of multi-omics approaches. Translational utility of NHP models requires further evaluation.

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.