Effects of chronic oxytocin administration on white matter microstructure in autistic adults: a pilot pharmaco-neuroimaging DTI study

Intranasal oxytocin is a promising therapeutic approach for social and stress-regulatory difficulties in autism spectrum disorder. However, there is limited understanding regarding whether chronic administration regimes can induce neuroplastic changes at the brain’s anatomical level and how such microstructural changes might underlie clinical-behavioral effects. This placebo-controlled pilot assessed the effects of a four-week oxytocin regimen (24 IU daily) on white matter microstructure in 27 young adult men with autism. Diffusion tensor imaging was performed at baseline, post-treatment, and after four-week and one-year retention periods. Tractography focused on fractional anisotropy (FA) in amygdala-centered tracts associated with socio-emotional processing: the bilateral Inferior Longitudinal Fasciculus (ILF), Inferior Fronto-Occipital Fasciculus (IFOF), and Uncinate Fasciculus (UF). Following four weeks of oxytocin administration, a spatially selective impact of intranasal oxytocin administration was demonstrated, indicating bilateral improvements in UF integrity and a hemispherically lateralized pattern of changes for the ILF and IFOF tracts, with FA increases predominantly emerging in the right hemisphere, while reductions were evident in left-sided segments. Especially for bilateral UF and right IFOF, the observed changes were clinically relevant, correlating with enhanced social responsiveness and reduced feelings of avoidant attachment. In conclusion, exploratory findings from this pilot neuroimaging trial suggest that a four-week oxytocin regimen may induce long-lasting neuroplastic changes in white-matter tracts relevant to behavioral improvements in adult men with autism. These hypothesis-generating findings may inform future confirmatory trials. Further investigation of the neuroplastic changes associated with oxytocin’s clinical and behavioral effects may help refine oxytocin-based interventions, not only for autism but also for other neuropsychiatric conditions in which oxytocin is being explored as a potential therapeutic option.