Brain Response to Fearful Faces in ASD with Regression: Research Update

Background:  Autism spectrum disorders (ASD) are disorders of early brain development, their ultimate phenomenology thought to be a manifestation of the cumulative results of an atypical developmental trajectory. However, some children undergo regression, developing ASD after a period of typical development, a natural history of illness that is difficult to reconcile with a cumulative explanation.  This suggests the possibility of a distinct pathophysiological process. These include children with the diagnoses of Childhood Disintegrative Disorder (CDD) as well as children with other ASDs that appear after a period of normal development. The initial period of typical development of children with regression suggests that the early development of the social brain may follow a typical trajectory, raising the possibility that aspects of its social function will be preserved and evident on functional scanning. 

Objectives: To compare subjects with regressive ASD to subjects with non-regressive ASD and typical subjects in terms of brain response to fearful faces.  

Methods:

Subjects with regression were defined by positive response to Autism Diagnostic Interview questions 11 and 20, with further detail provided by ADI loss supplement, and a detailed developmental history conducted by a clinician with expertise in regression in ASD.  Subjects were only included if they experienced a regression in multiple domains at greater than twenty months of age.  Subjects with an ASD, but less dramatic regression were excluded from the analyses. Using a task designed to probe functional characteristics of the social brain, we compared subjects with ASD (n=34) to those with regressive ASD (n=19) and typical controls (n=19) using fMRI (whole-brain scanning, TR = 2s, 3T MRI scanner). Participants with an ASD met diagnostic criteria by the Autism Diagnostic Observation Scales (ADOS) and ADI scores and clinical evaluation. IQ was measured by overall Differential Ability Scales (DAS) scores, except for several cases of low-functioning children when ratio estimations were made (mental/ chronological age). 

Results:  Preliminary results of a group comparison between the subjects typical subjects and those with non-regressive ASD are consistent with previous studies, suggesting distinguishing patterns of activation in key nodes of the social brain including the right superior temporal sulcus and bilateral amygdalae in response to fearful faces.  Preliminary results of a group contrast between the subjects with regressive ASD and non-regressive ASD indicate significant differences in the right superior temporal sulcus and amygdalae, with the regressive ASD subjects exhibiting patterns of activation more consistent with typical development. 

Conclusions:  Preliminary data supports the hypothesis that there are functional differences in the activation of several brain areas related to the processing of social information when subjects with regressive ASD are compared to their peers with non-regressive ASD as well as their typically developing peers,  supporting the hypothesis that the differences in the onset patterns of ASD may reflect distinct mechanisms.