A Volumetric and Functional Connectivity MRI Study of Brain Arginine-Vasopressin Pathways in Autistic Children

Dysfunction of brain-derived arginine-vasopressin (AVP) systems may be involved in the etiology of autism spectrum disorder (ASD). Certain regions such as the hypothalamus, amygdala, and hippocampus are known to contain either AVP neurons or terminals and may play an important role in regulating complex social behaviors. The present study was designed to investigate the concomitant changes in autistic behaviors, circulating AVP levels, and the structure and functional connectivity (FC) of specific brain regions in autistic children compared with typically developing children (TDC) aged from 3 to 5 years. The results showed: (1) children with ASD had a significantly increased volume in the left amygdala and left hippocampus, and a significantly decreased volume in the bilateral hypothalamus compared to TDC, and these were positively correlated with plasma AVP level. (2) Autistic children had a negative FC between the left amygdala and the bilateral supramarginal gyri compared to TDC. The degree of the negative FC between amygdala and supramarginal gyrus was associated with a higher score on the clinical autism behavior checklist. (3) The degree of negative FC between left amygdala and left supramarginal gyrus was associated with a lowering of the circulating AVP concentration in boys with ASD. (4) Autistic children showed a higher FC between left hippocampus and right subcortical area compared to TDC. (5) The circulating AVP was negatively correlated with the visual and listening response score of the childhood autism rating scale. These results strongly suggest that changes in structure and FC in brain regions containing AVP may be involved in the etiology of autism.