Consistent with our predictions, we found thinner cortex predominantly in left temporal and parietal cortices in high functioning adolescent and young adult males (ages 12–24 years) with autism spectrum disorders relative to a well-matched group of typically developing males. We also found evidence for group differences between the autism spectrum disorders and typically developing groups in age-related cortical thickness changes. Individuals with autism spectrum disorders >17 years of age, relative to individuals with autism spectrum disorders ≤17 years, had robustly thinner (particularly temporal) cortex, while such age-related patterns in the typically developing group were less pronounced. Our study, by focusing on the relatively understudied period of adolescence and young adulthood, adds to a growing body of work on developmental trajectories in autism spectrum disorders. Specifically, our findings suggest that, in addition to the well-documented early brain overgrowth in autism spectrum disorders, there is probably prematurely arrested growth during the late childhood/early adolescent age range, followed by accelerated regionally specific thinning during adolescence and young adulthood.
More specifically, the present results complement earlier findings of thinner cortex in adults with autism spectrum disorders (Chung et al., 2005
; Hadjikhani et al., 2006
; Wallace et al., 2009
) and may therefore pinpoint adolescence as the time window during which the cortical growth trajectories diverge a second time (in addition to the overgrowth during early development). Taken from this perspective, these findings somewhat parallel those previously reported for amygdala volumes; the amygdala was found to be significantly larger among pre-adolescent children (ages 7.5–12.5 years) with autism spectrum disorders versus typically developing children in this age range, while similar amygdala volumes were reported for adolescents (ages 12.75–18.5 years) with autism spectrum disorders versus their same age typically developing peers (Schumann et al.
, 2006). Placed in the context of the wider literature, the current findings suggest that the presence of thinner cortex continues into young adulthood, although it is unclear whether the cortical developmental trajectory in autism spectrum disorders across childhood, adolescence and young adulthood is parallel to that found in typical development. Longitudinal studies are needed to validate this proposed accelerated cortical thinning during adolescence and young adulthood in autism spectrum disorders.
The regional specificity of the present findings was largely consistent with prior studies (that have documented both thinner and thicker cortex in autism spectrum disorders depending on the age group studied). As in the present study, thinner temporal and parietal cortices, particularly in the left hemisphere, were also documented by Hadjikhani et al. (2006)
and Wallace et al. (2009)
among high-functioning adult males on the autism spectrum. Hardan et al. (2006)
measured cortical thickness over lobar regions, finding that thicker cortex in autism spectrum disorders was restricted to temporal and parietal cortices during childhood, just as thinner cortex was confined to those regions in our sample of adolescent and young adult males with autism spectrum disorders. Similarly, the more pronounced age-related cortical thinning in autism spectrum disorders documented in the current study was confined to the temporal cortex, corresponding to Hardan et al.’s (2009)
longitudinal study finding accelerated thinning in the temporal cortex in the autism spectrum disorders group. In the context of a large cross-sectional study (autism spectrum disorders n
76), Raznahan et al. (2010)
also found significant age
diagnosis interactions, primarily in the temporal cortex. However, the pattern of group differences was discrepant from those shown here. While we found more pronounced cortical thinning in individuals with autism spectrum disorders than in typically developing individuals, Raznahan et al.
found relatively flat age-related changes in the temporal cortex in the autism spectrum disorders group, unlike the typically developing group, which displayed thinner temporal cortex with increasing age. The different age ranges studied and the modelling chosen in that study very likely contributed to inconsistent findings. While our study concentrated on adolescence and young adulthood (associated with a linear decline in cortical thickness), their study encompassed a much larger age band, with individuals ranging in age from 10 to 60 years (periods of both decline and levelling off of cortical thickness developmental curves, suggesting that their use of linear models may be problematic). Additionally, their findings do not fit the general pattern in the literature of increased cortical thinning in autism spectrum disorders at later ages. Finally, participants with autism spectrum disorders in their study, as in most other studies of cortical thickness in autism spectrum disorders, were not matched to the control group on IQ. Instead, any IQ effects were accounted for via covariation only.
Coupled with findings of early overgrowth, the increasingly thinner cortex during adolescence and young adulthood could reflect a leftward shift in autism spectrum disorders of the inverted U-shaped pattern of grey matter observed for both volumes and cortical thickness during typical development (Giedd et al., 1999
; Shaw et al., 2008
), perhaps reflecting synaptogenesis/neurogenesis gone awry. It could be that, in autism spectrum disorders, early cortical overgrowth is followed by either earlier synaptic pruning or over-pruning during adolescence, a period characterized by selective synaptic elimination and arborization of dendrites and axons (Huttenlocher and Dabholkar, 1997
). We are reassured that findings reported in the present study do not simply reflect tissue compartmental shift (i.e. as grey matter decreases, white matter increases), given that white matter volume in our sample is either not different between groups or indeed smaller in the autism spectrum disorders group. Similarly, whether or not a participant with autism spectrum disorders was taking psychotropic medication or exhibited clinically elevated psychopathology did not change the pattern of results. This rules out medication usage and comorbid psychopathology as contributory factors to our findings of cortical thinning, and furthermore, suggests that the cortical thinning documented here is a result of autism spectrum disorders, not comorbid conditions. What genetic and/or environmental forces contribute to this abnormal cortical growth trajectory remain unknown, although it is well established that brain volumes (Wallace et al., 2006
), and to a lesser extent cortical thickness (Lenroot et al., 2009
), during childhood and adolescence are highly heritable. Recently, Wassink and colleagues (2007)
linked cortical grey matter overgrowth in autism spectrum disorders with variation of the serotonin transporter gene, though Raznahan and colleagues (2009)
could not replicate this result. Davis et al. (2008)
also linked cortical enlargement in autism spectrum disorders with the ‘low activity’ allele of the Monoamine oxidase A (MAOA) gene. The cortical growth trajectory in autism spectrum disorders may also vary for individuals with optimal versus more typical outcomes, as has been shown in attention-deficit/hyperactivity disorder (Shaw et al., 2006b
). Future research should continue to explore links between genetic/environmental factors and this atypical trajectory of brain growth, particularly focusing on cortical thinning, in autism spectrum disorders.
Although these results are promising, there are limitations to consider. First, the present study included only high-functioning males; therefore, this pattern of findings may not apply to either lower functioning individuals or females with autism spectrum disorders. This study focused on high-functioning individuals with autism spectrum disorders in order to better isolate autism spectrum disorders-specific effects on cortical thickness, above and beyond intellectual disability and because prior studies demonstrated significant associations between IQ and cortical thickness (Shaw et al., 2006a
; Narr et al., 2007
). Additionally, the sample was restricted to males, because previous work reveals sex differences in neuroanatomy, not only in typical development (Lenroot et al., 2007
), but also in autism spectrum disorders (Bloss and Courchesne, 2007
; Craig et al., 2007
; Schumann et al., 2010
). Finally, this investigation was cross-sectional in design, though larger than previously reported similar studies. Longitudinal designs, such as those conducted by Schumann et al. (2010)
in early development and Hardan et al. (2009)
in late childhood, are needed in later developmental windows to more definitively test postulations surrounding the cortical growth trajectory in autism spectrum disorders.
Much has been made of the unique and atypical early brain overgrowth in autism spectrum disorders, perhaps to the relative detriment of later developmental changes in this group. In order to fully understand the pattern of neural growth and development in autism spectrum disorders, a snapshot of various developmental windows is required, as we have done here for the period of adolescence and young adulthood. Once this pattern of atypical development has been established via cross-sectional and longitudinal studies, we can begin to investigate genetic and environmental mechanisms as well as intervention effects on this trajectory.