Title: Brain Responses to Fearful Faces Differentiate Childhood Disintegrative Disorder From Other Autism Spectrum Disorders

Background: Childhood disintegrative disorder (CDD) is defined by normal development for at least two years of life, followed by regression of social and language development, and the onset of repetitive behavior patterns. During the period of acute regression, behavioral dysregulation occurs characterized by severe anxiety that may reflect disruption in amygdala function. Once the regression is complete, however, CDD is clinically similar to Autism Spectrum Disorder (ASD) with Intellectual Disability. Research on CDD is scarce due to its association with low intellectual and adaptive function and its rare occurrence. This disorder is particularly interesting given that the natural history suggests an acquired disorder rather than a developmental process of the kind thought to underlie other ASDs. Thus, examining the brain mechanisms of CDD may inform our understanding of ASD. This is the first neuroimaging study of children with CDD.

Objectives: We used functional magnetic resonance imaging to capture brain responses to fearful faces and houses in children with CDD relative to children with ASD (both with and without ID) and typically developing (TD) children. The passive-viewing task was designed to drive the amygdala, fusiform, and superior temporal sulcus (in response to fearful faces) and the parahippocampal gyri (in response to houses). On the basis of the fact that CDD is marked by an anxiety prodrome, we hypothesized that children with CDD would exhibit distinct amygdala activity in response to fearful faces relative to children with ASD. On the basis of the similarity in ultimate presentation, we hypothesized that the CDD and ASD groups would exhibit similar hypoactivation to faces in the right fusiform gyrus and superior temporal sulcus. We predicted that all groups would exhibit equivalent response to houses in the parahippocampal gyri.

Methods:  The CDD (n=3) and ASD with ID (n = 4) groups both had severe to profound intellectual disability. The ASD without ID (n = 13) and TD groups (n = 11) were matched on IQ. Participants viewed gray-scale images of 30 fearful faces from the NimStim Face Stimulus Set and 30 houses in two series of ten alternating blocks, each lasting 12 seconds, for a total of 320 seconds. Face and house stimuli were matched on luminosity, resolution, size, and contrast.

Results: We examined neural response to faces versus house in each of the anatomically defined regions described above. We observed amygdala response to fearful faces > houses in the TD children. However both the CDD and the ASD groups did not appear to exhibit differential activation to faces vs. houses. We observed robust right superior temporal sulcus and fusiform gyrus activity to faces > houses in both the typically developing children and those with CDD, but not in the other ASD groups.. Equal levels of houses > faces activity was observed in all groups in the parahippocampal gyri.

Conclusions: CDDs appear to be distinguishable from TD on the basis of amygdala activity, and from other ASDs on the basis of right superior temporal sulcus and fusiform gyrus activity when viewing alternating blocks of fearful faces and houses.