Investigating cerebral blood flow dysregulation and serum zinc correlation in 2-4 year-old children with autism spectrum disorder

Abstract

Background: Autism spectrum disorder (ASD) is a severe neurodevelopmental condition. Its incidence is on the rise worldwide, and in severe cases, it can lead to disability. While emerging evidence implicates cerebrovascular dysfunction in the pathophysiology of neurodevelopmental impairments associated with ASD, systematic characterization of cerebral hemodynamic variations across clinically stratified severity subgroups, particularly among mild-moderate and severe ASD presentations and typically developing (TD) children, remains a critical unmet research need.

Methods: This cross-sectional neuroimaging study enrolled 121 children aged 2 to 4 years: 16 with severe autism (Childhood Autism Rating Scale (CARS) score > 36), 60 with mild-moderate autism (CARS score between 30 and 36), and 45 TD children. CBF measurements were obtained from nine regions of interest (ROI) in both hemispheres: temporal lobe, parietal lobe, occipital lobe, putamen, thalamus, caudate nucleus, globus pallidus, hippocampus, and amygdala. Intergroup comparisons of CBF values were performed among the three groups. Particular emphasis was placed on analyzing the correlation between thalamic CBF values and serum zinc levels in autistic children.

Results: Children with severe autism exhibited significantly lower CBF in the temporal lobe, putamen, thalamus, and hippocampus compared to TD children (p < 0.05). Within the autism cohort, severe cases demonstrated further CBF reductions in the putamen and thalamus compared to mild-moderate cases (p < 0.05). Similarly, children with mild-moderate autism showed reduced CBF in the temporal lobe, putamen, thalamus, and hippocampus compared to TD children (p < 0.05). Notably, a significant difference in CBF was observed between the left and right thalamus in both mild-moderate and severe autism groups, with lower blood flow in the left thalamus (p < 0.05). A positive correlation was found between thalamic CBF values and serum zinc levels in the autism group.

Conclusions: Children with severe autism show significantly reduced CBF in critical brain regions. Thus, 3D-pCASL may enable the precise stratification of ASD severity in children and provide an imaging foundation for subsequent therapeutic evaluation.

Keywords: 3D-pCASL; ASD; Cerebral blood flow; Neurophysiology; Zinc.