Abstract
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.
Highlights
Autism spectrum disorder (ASD) is a developmental disorder with a high incidence and the symptoms may be lifelong
Children with autism spectrum disorder (ASD) and typically developing children (TDC) were matched for age (t = 1.465, P = 0.1548) and gender (v2 = 0.849, P = 0.3570)
The results showed that the volumes of the left amygdala (1.39 ± 0.18 cm3 for ASD, 1.27 ± 0.11 cm3 for TDC; F = 4.520, P = 0.045) and the left hippocampus (3.54 ± 0.44 cm3 for ASD, 3.24 ± 0.39 cm3 for TDC; F = 4.548, P = 0.043) were significantly enlarged in children with ASD
Summary
Autism spectrum disorder (ASD) is a developmental disorder with a high incidence and the symptoms may be lifelong. Several lines of evidence suggest that dysfunction of the AVP and/or OXT system in these areas may be involved in the pathogenesis of ASD These peptides are known to be heavily involved in the regulation of complex social cognition and behaviors [8,9,10,11], and impairment in social interaction is one of the core symptoms in ASD. Both AVP and OXT have been shown to play roles in neural development, and their receptors are highly expressed and constantly remodeled in the immature brain [7, 12,13,14]. Similar sexual dimorphism has been noted in children with ASD
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