Potential mechanisms and research progress of animal-assisted interventions for autism spectrum disorder

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with onset in early childhood. Conventional behavioral interventions are limited by poor adherence and variable efficacy. Animal-assisted intervention (AAI) creates a low-stress therapeutic environment through positive human-animal interaction and has become an important adjunctive approach for ASD. This review summarizes the clinical evidence, underlying mechanisms, and current limitations of AAI. Clinical evidence indicates that dog-assisted and equine-assisted interventions can improve core symptoms and common comorbidities. However, treatment effects are highly heterogeneous, effect sizes vary widely, several high-quality studies have reported no significant benefit, and the overall level of evidence remains low. Mechanistically, AAI may act through multiple pathways involving neurobiological regulation, physiological and immune modulation, psychological and behavioral processes, and sensorimotor integration. To date, only hypothalamic-pituitary-adrenal axis regulation, autonomic nervous system modulation, and social brain network remodeling have gained preliminary direct support. Synaptic plasticity, immune-inflammatory regulation, and mitochondrial metabolism remain largely hypothetical. Optimal mechanisms may differ across ASD subgroups, requiring stratified intervention based on age, cognitive level, and sensory characteristics. In addition, stress in therapy animals is not only an ethical concern but also a confounding factor that may affect attribution of treatment effects. Current evidence is limited by the lack of high-quality randomized controlled trials, heterogeneous intervention assessment, and insufficient mechanistic evidence. Future research should prioritize large-scale randomized controlled trials, distinguish direct from indirect evidence, include animal stress in statistical analyses, and develop personalized intervention strategies to advance standardized, evidence-based AAI practice.

Keywords: Animal-assisted intervention; Autism spectrum disorder; Neurobiological mechanisms; Clinical rehabilitation; Social communication

Core Tip: This review evaluates clinical evidence and mechanisms of animal-assisted intervention (AAI) for autism spectrum disorder. Clinically, dog- or equine-assisted interventions improve symptoms and comorbidities, but efficacy is highly heterogeneous with variable effect sizes, and several high-quality studies demonstrate no significant benefit, indicating low-quality evidence. Mechanistically, AAI regulates hypothalamic-pituitary-adrenal axis, oxytocin, social brain networks, autonomic function, and sensorimotor integration. However, direct evidence is limited to neuroendocrine responses, heart rate variability, and electroencephalographic changes; synaptic plasticity, immune regulation, and mitochondrial metabolism remain theoretical. Optimal mechanisms differ by subgroup, highlighting stratification by age, cognition, and sensory characteristics. Methodologically, animal stress is a confounder affecting interaction quality. Future trials are supposed to include animal stress as a covariate and establish stratified frameworks for standardized, evidence-based AAI practice.