The Anatomy and Aging of the Amygdala-Hippocampal Complex in Autism Spectrum Disorder

Background: It has been proposed that people with autism spectrum disorder (ASD) have abnormal morphometry and development of the amygdala-hippocampal complex (AHC). However, previous reports of AHC in ASD are inconsistent – perhaps because they included people from different parts of the spectrum, of variable ages and health characteristics.  Moreover nobody has investigated the genetic and biochemical influences on differences in AHC.

Objectives: We carried out two related studies of people with ASD (defined as scoring above cut-off on the Autism Diagnostic Interview, Revised (ADI-R)).  In the first we investigated the anatomy, and age-related differences, in the AHC of 32 healthy individuals with ASD aged 9 – 68 years, and 32 healthy matched controls.  In the second we investigated if variation in genes which regulate glutamate and GABA contribute to differences in development.  Specifically we examined if genetic variation in Glutamic Acid Decarboxylase (GAD) 65 modulates the anatomy of entorhinal cortex.

Methods: MRI

Results: Individuals with AS had a significantly larger raw bulk volume of amygdala (p < 0.01), and when corrected for whole brain size (p < 0.01).  Also there was a significant difference in age-related effects with controls, but not individuals with AS, having a significant age-related increase (respectively; r = 0.486, p < 0.01, r = 0.007, p = 0.97). There were no significant differences in volume or age-related effects in hippocampus. Lastly, we found a significant association between variation in GAD65 and increase in volume.

Conclusions: Young people with ASD have a significant difference in volume and aging of the AHC, and this not simply accounted for by a generalised difference in brain.  Genes which modulate the concentration of glutamate and GABA may play a crucial part in the abnormal developmental process.