Preliminary Findings From a Longitudinal Examination of Brain Volume From 6 to 24 Months in Infants At High Familial Risk for Autism

Background: Multiple lines of converging evidence from post-mortem, magnetic resonance imaging, and head circumference studies have documented brain and head size enlargement in autism spectrum disorder (ASD). This brain enlargement has been observed as early as age 2.  Data from longitudinal head circumference studies as well as behavioral studies of infant siblings at high risk for autism suggest that key developmental changes associated with ASD may occur in the first year of life. 

Objectives: We sought to characterize trajectories of early brain growth in infants at high familial risk for autism. We examined longitudinal brain volumes using structural MRI data from a large sample of 6 month olds at high risk for autism and typically-developing controls with follow-up scans at ages 12 and 24 months.  

Methods: Imaging data was obtained from all four IBIS data collection sites.  Data collection included a battery of behavioral and developmental assessments and structural MRI and DTI scans obtained on a 3T Siemens scanner. This longitudinal study is currently ongoing, so we are reporting on preliminary findings from the longitudinal data we have collected thus far. Brain volume measures were performed on 112 high-risk and 17 low-risk controls infants at age 24 months who had previous scan data at 6 and/or 12 months of age.  Brain measures at 6 months included intracranial volume (ICV), total brain volume (TBV), cerebrum, cerebellum, and head circumference. At ages 12 and 24 months, we were also able to examine the tissue volume of the cortical lobes (frontal, temporal, parietal, occipital) as well as cortical surface area and thickness.  Statistical analyses included covariates such as gender, site, body size (length), and age at scan. 

Results: Scores on the ADOS-G were used to classify children in the HR group.  There were 31 HR infants who fell on the autism spectrum (ASD+) and 71 infants who did not meet ASD criteria.  To account for body size differences in evaluation for brain growth, we calculated normative age for body size based on The WHO Child Growth Standards (boy). We compared the group differences in brain growth rate in relation to normative body growth, and found an increased rate of total brain volume (TBV) growth in male HR infants who are classified as ASD+ at 24 months compared to the non-spectrum HR infants and low-risk controls. This pattern of increased growth rate between 6 – 24 months was also seen for gray and white matter volumes.

Conclusions: The preliminary results from this ongoing study suggest the presence of an  increased rate of brain volume between ages 6 to 24 months in infants at high-risk for autism who fall on the autism spectrum at age 24 months.  These findings suggest that early differences in brain growth emerge in the first two years of life and raise the optimistic possibility that there is a window of opportunity where early postnatal intervention, during a period of tremendous brain plasticity, may have an important impact on the later emergence of autistic behavior.