Targeting exercise triggered irisin for therapeutic intervention of autism-associated social anxiety.

Researchers reviewed whether a hormone called irisin, which is released when we exercise, might help reduce social anxiety in autistic people. Studies in animals suggest irisin can improve social behavior and reduce anxiety by affecting the brain in helpful ways. While exercise has been shown to reduce anxiety in autistic people, more research is needed to prove irisin is the reason why. The findings suggest exercise programs could be designed specifically to help autistic people with social anxiety.

This review examines the therapeutic potential of irisin, a hormone released during exercise, for treating social anxiety in autism spectrum disorder (ASD). Irisin crosses the blood-brain barrier and influences several neurobiological pathways relevant to ASD, including enhancing brain plasticity through BDNF upregulation, reducing neuroinflammation by modulating immune cells, and normalizing stress responses. Preclinical studies in rodent models show irisin improves social behavior and reduces anxiety. Clinical studies demonstrate exercise correlates with reduced anxiety in people with ASD, though direct irisin measurements are limited.

The authors suggest irisin could be targeted through optimized exercise programs or potential pharmacological approaches, despite challenges with exercise adherence in ASD populations.

Irisin represents a potential biological target for developing exercise-based interventions for social anxiety in ASD. However, more research is needed to establish direct irisin-anxiety relationships in humans with ASD and to develop practical exercise protocols that account for adherence challenges in this population.

Direct irisin measurements in clinical ASD studies are limited. Heterogeneity in exercise responsiveness and adherence challenges in ASD populations are noted concerns. As a review paper, findings depend on quality and consistency of underlying studies reviewed.

Autism spectrum disorder (ASD) is frequently complicated by debilitating social anxiety, which exacerbates social impairments and reduces quality of life. This review explores the therapeutic potential of exercise-induced irisin, a myokine released during physical activity, in mitigating ASD-associated social anxiety. Irisin, derived from the cleavage of skeletal muscle FNDC5 protein, crosses the blood-brain barrier and modulates key neurobiological pathways implicated in ASD. It enhances neurogenesis and synaptic plasticity via BDNF upregulation, suppresses neuroinflammation by reprogramming microglia and reducing pro-inflammatory cytokines, and normalizes HPA axis hyperactivity to reduce stress responses.

Preclinical evidence demonstrates irisin's efficacy in improving social behaviour and reducing anxiety in ASD rodent models, while clinical studies correlate exercise with reduced anxiety in ASD individuals, though direct irisin measurements remain limited. Despite heterogeneity in exercise responsiveness and adherence challenges in ASD populations, irisin represents a promising endogenous mediator for novel therapeutic strategies, including optimized exercise regimens and pharmacological mimetics.