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

Background: Children with autism often exhibit impairment in socioemotional processing and enhanced stress in novel situations. The amygdala, which is involved in these processes, has long been implicated in the neuropathology of autism. Previously we have reported significant variability in diurnal regulation and stress responsivity of cortisol in children with autism. Similarly, we have shown notable variability in the volume of the amygdalae in autism, and subsequent within-group analysis revealed that smaller right amygdala volume was associated with more social anxiety.

Objectives: The current investigation was designed to compare neuroimaging and psychobiological data across study participants to determine if an association exists between cortisol stress responsivity and amygdala volume.

Methods: The study included 26 children ages 8-to-12 years old with autism (n=12) and typical development (n=14) that participated in the cortisol regulation and responsivity and neuroimaging protocols. Using correlation analysis and linear regression we: 1) compared the relationship between amygdala volume and cortisol across participants, 2) assessed associations between stress, amygdala volume and diagnosis, and 3) evaluated the relationship between stress responder status and amygdala volume in autism.

Results: There was no relationship between amygdala volume and cortisol across all of the participants or based exclusively on diagnosis.  However, within the autism group, a subset emerged in children with autism that were classified as cortisol stress Responders, a classification based on elevated cortisol responsive to a stressor.  The autism Responders had smaller right amygdala (t(9) = -2.73, p=0.02) and smaller left amygdala (t(9) = -3.08, p=0.01).  There were no associations for autism Nonresponders or the typical Responder and Nonresponder groups.

Conclusions: The preliminary findings provide evidence for an association between enhanced LHPA responsivity and smaller amygdala in a subset of children with autism. Interestingly, smaller amygdalae have been associated with pediatric anxiety. The current findings, albeit preliminary, support our emerging hypothesis of a neuroendocrine spectrum model of autism in which individuals may ultimately be phenotyped by their stress reactivity, social anxiety and brain structure and function, which may facilitate the development of targeted treatments.