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Objectives: Identifying an objective, laboratory-based diagnostic tool (e.g. changes in gene expression), when used in conjunction with disease-specific clinical assessment, could increase the accuracy of the effectiveness of a therapeutic intervention. Methods: We assessed the association between treatment outcome and blood RNA expression before the therapeutic intervention to post-treatment (after 1 year) of five autism spectrum disorder (ASD) toddlers who underwent an intensive cognitive-behavioural intervention integrated with psychomotor and speech therapy. Results: We found 113 significant differentially expressed genes enriched for the nervous system, immune system, and transcription and translation-related pathways. Some of these genes, as MALAT-1, TSPO, and CFL1, appear to be promising candidates. Conclusions: Our findings show that changes in peripheral gene expression could be used in conjunction with clinical scales to monitor a rehabilitation intervention’s effectiveness in toddlers affected by ASD. These results need to be validated in a larger cohort.

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