The Effect of Age and Symptom Severity On Brain Surface Area In Autism Spectrum Disorders

Background:  Grey matter volume (GMV) abnormalities have been reported in individuals with Autism Spectrum Disorders (ASD) (Courchesne 2010).  However, what determinants of GMV contribute to these atypicalities is still unknown.  Cortical thickness and surface area are both components of GMV that capture distinct neurobiological processes (for reviews see Anagnostou and Taylor, 2011; Raznahan et al., 2010).  Atypical development of cortical thickness in a number of brain regions in people with ASD have previously been found (Wallace et al., 2010; Raznahan et al., 2010; Mak-Fan et al., 2011), with some atypicalities related to social impairment (Hardan et al., 2009; Hadjikhani et al., 2006).

Objectives: To examine the developmental trajectory of surface area (the other determinant of grey matter volume) in ASD and determine if abnormalities are related to symptomatology. 

Methods:  High-resolution anatomical Magnetic Resonance Imaging (MRI) scans from 53 individuals with (n=29) and without (n=24) ASD between the ages of 7 and 39 (ASD mean age=22 ±8 years; 22 males; control mean age = 21±9 years; 18 males) were included in this analysis.  ASD participants carried a clinical diagnosis, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) and their diagnoses were confirmed using the Autism Diagnostic Observational Schedule (ADOS) and the Autism Diagnostic Interview - Revised (ADI-R). All participants had an IQ>70 as estimated by the Wechsler Intelligence Scale for Children-fourth edition (WISC-IV) or the Wechsler Adult Intelligence Scale-fourth edition (WAIS-IV).  Surface area was estimated for the whole brain, each cortical lobe, the para-splenium, the parahippocampal gyrus, the anterior cingulate cortex (ACC) and the insula cortex based on surface-to-surface deformations (Lyttelton et al., 2007; Boucher et al., 2009).  Effects of age, group and symptomatology on surface area were examined using regression analyses.    

Results: At a significance level of 0.05, an age x group interaction was found for surface areas in the right ACC (p=0.04) and the right para-splenium (p=0.02).  In the ASD group, a significant relation was observed between ADI-R scores and surface area in the right insula (p=0.03), with more severe social impairment related to increased surface area in this region.  These results however did not survive adjustments for multiple comparisons.         

Conclusions: The findings of the present study suggest potential regions of interest for future investigations on the development of surface area in ASD.  The right ACC and insula are both brain regions implicated in social function and are key areas of functional impairment in ASD. Atypical surface morphometry in these regions may indicate a neurobiological contributor to social impairment observed in ASD. Indeed, these results suggest that abnormalities in the insula may be associated with social symptom severity.  In a previous study (Doyle-Thomas et al., under revision), atypical cortical thickness was found in the ACC and collectively, these findings may suggest general abnormalities in GMV in this brain region.  This raises the question of whether atypical development in components of GMV in social brain areas may be an intermediate phenotype that may be explored further for neurobiological and potential treatment research.