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

Figure 1 PRISMA 2020 flow diagram of the literature identification, screening and inclusion process. A systematic search of five databases (PubMed, Web of Science, Scopus, PsycINFO, and CNKI) identified 2381 records. After removing 503 duplicates, 1878 records were screened by title and abstract, of which 1245 were excluded. Of the 633 reports sought for retrieval, 9 were not accessible. The remaining 624 full-text reports were assessed for eligibility, and 340 were excluded primarily for inconsistent intervention definitions or irrelevant outcomes. The final review included 284 studies, comprising 67 randomized controlled trials, 96 non-randomized or pre-post studies, 42 cross-sectional or observational studies, 23 qualitative studies, and 56 systematic reviews or meta-analyses. Numbers represent the number of records at each stage. ASD: Autism spectrum disorder.

Figure 2 Proposed mechanistic framework of animal-assisted intervention for autism spectrum disorder. Animal-assisted intervention may exert its therapeutic effects through four interconnected pathways: Neurobiological regulation (hypothalamic-pituitary-adrenal axis modulation, oxytocin system activation, brain network remodeling, and neuroplasticity enhancement), physiological and immunometabolic modulation (autonomic nervous system regulation, cytokine balance restoration, and mitochondrial function improvement), psychological-behavioral facilitation (emotional security, social motivation, behavioral synchrony, and self-control), and sensorimotor integration (vestibular, proprioceptive, and multisensory input processing). These pathways converge to improve core autism spectrum disorder symptoms. HPA: Hypothalamic-pituitary-adrenal; mPFC: Medial prefrontal cortex; BDNF: Brain-derived neurotrophic factor; mTOR: Mammalian target of rapamycin; AAI: Animal-assisted intervention; HRV: Heart rate variability; IL: Interleukin; TNF-α: Tumor necrosis factor-α; INN: Interneuron network; ATP: Adenosine triphosphate; ASD: Autism spectrum disorder.