Exploring the Association Between Total Cerebral Volume and Cortisol Responsivity in Children with Autism

Background: Children with autism often exhibit enhanced stress in novel situations. The idea of an association between symptoms of anxiety and total cerebral volume has been proposed. Previously, we have reported significant variability in the stress responsivity of cortisol in children with autism. Similarly, we saw notable variability and a lack of gross difference in total cerebral volume between individuals with autism and control subjects. However, differences have been shown with some reports indicating cerebral enlargement. Distinctions based on age have been highlighted, hypothesizing an early, rapid brain overgrowth followed by a prolonged slowing of brain growth.

Objectives: This study was designed to compare neuroimaging and psychobiological data across study participants to determine if an association exists between cortisol stress responsitivity and total cerebral volume.

Methods: This study compared structural MRI data of overall cerebral volume with cortisol reactivity in 26 children with high functioning autism (n=12) and typical development (n=14). Using correlation analysis and linear regression we: 1) compared the relationship between total cerebral volume and cortisol across participants, 2) assessed associations between stress, total cerebral volume and diagnosis, and 3) evaluated the relationship between stress responder status and total cerebral volume in autism.

Results: There was no association between total cerebral volume and cortisol across participants or between diagnostic groups. However, within the autism group, a subset emerged showing that children classified as cortisol stress Responders, based on responsivity of the limbic-hypothalamic-pituitary-adrenal (LHPA) system to a stressor, had larger total cerebral volume (t(8) = 2.24, p=0.04).

Conclusions: The association between stress responsivity and brain structure identifies a possible subset of autistic children while explaining some of the variance in MRI findings across studies.