Therapeutic Application of Repetitive Transcranial Magnetic Stimulation in Patients with Autism Spectrum Disorder: A Randomized, Double-Blind, Sham-Controlled Pilot Study

This study investigated the behavioral, cognitive, and biochemical effects of repetitive transcranial magnetic stimulation (rTMS) in a pediatric population, with assessments conducted at three time points: pre-treatment (T1), post-treatment (T2), and one month post-treatment (T3). Behavioral outcomes were measured using the Child Behavior Checklist (CBCL), the Childhood Autism Rating Scale (CARS), and the Children’s Depression Inventory (CDI), while cognitive performance was evaluated through the Leiter International Performance Scale-Revised (Leiter-R). Biochemical markers were also analyzed to explore neuroinflammatory and neurotransmitter pathways involved in the treatment response. The results indicated a significant increase in aggressive behavior over time, observed exclusively in the Sham group, suggesting a stabilizing effect of rTMS on externalizing symptoms. A delayed improvement in sociality was detected in the rTMS group between T2 and T3, supporting the hypothesis of time-dependent behavioral benefits. Regarding autistic symptomatology, CARS scores showed significant group differences and a significant Group × Time interaction, with improvements emerging one month after treatment. No significant changes in depressive symptoms were observed, as CDI scores remained stable across groups and time points. Cognitive outcomes revealed a significant IQ increase in the rTMS group at T3. Individual analysis highlighted major improvements in two patients, suggesting potential cognitive benefits beyond test fluctuations. Biochemical analyses supported the behavioral and cognitive findings, revealing a delayed rebound in plasma BDNF levels, progressive reductions in pro-inflammatory cytokines (IL-6 and IL-1β), and a modulation of the kynurenine pathway (decreases in TRP and 3-HKYN, increase in KYN levels). Moreover, shifts toward neuroprotective profiles were observed (reduced IDO/KMO ratio), along with transient dopaminergic activation and a significant inhibition of serotonergic activity (marked decrease in plasma 5-HT levels). Overall, these findings suggest that rTMS exerts multifaceted effects involving behavioral stabilization, cognitive enhancement, and modulation of neuroinflammatory and neurotransmitter systems. Further studies are warranted to confirm these preliminary results and to better elucidate individual variability in treatment response.