Are Early Neurophysiological Markers of ASD Syndrome-Specific? Preliminary Results From a Cross-Syndrome Study

Background: ASD is a neurodevelopmental disorder characterised by gross and sustained impairment of social interaction and communication. ASD diagnosis is by behavioural criteria, which do not emerge clearly until age two or three. As a consequence, little research has been done on the very early development of autism. Recent studies have begun to bridge this gap by carrying out prospective studies of younger siblings of children already diagnosed with ASD (Sibs). This is an important strategy because one in five Sibs goes on to an autism diagnosis. The British Autism Study of Infant Siblings (BASIS) is a large-scale prospective study, a key goal of which is to help clinicians and researchers identify early markers of autism. This will not only contribute to our understanding of ASD, but will also enable earlier, more effective interventions, which could significantly improve subsequent quality of life. Indeed, several early markers are already emerging. However, before a measure can be said to be an early marker of ASD, it is crucial to determine whether it is syndrome-specific. 

Objectives:  The aim of the present study is to determine whether BASIS measures yield syndrome-specific or syndrome-general findings, by testing infants/toddlers with other genetic syndromes (namely, Down syndrome (DS), fragile X syndrome (FXS), Williams syndrome (WS)) on the same battery of tasks. Here we present preliminary data from one of these tasks, which seek to elucidate the way in which infants/toddlers process changes in speech sounds and pitch. 

Methods:  Auditory event-related potentials were studied in infants/toddlers with DS (N=27), FXS (N=10), and WS (N=30). Sounds were presented oddball: 70% of the sounds were /u/ vowels (standards), 15% were /u/ vowels with a different pitch to the standards (pitch deviants) and 15% were /i/ vowels with the same pitch as the standards (speech deviants). The data were compared with data from Sibs (N=51) and controls (N=22), who had been tested on identical measures.

Results:  The infant equivalent of the preattentive mismatch negativity (MMN) in response to pitch deviants was found in all groups except in FXS, reflecting atypical discrimination of pitch in FXS. In response to speech deviants, the MMN occurred 150 ms late in WS (reflecting atypical discrimination). The P3a component (attentive orientation) in response to speech deviants was seriously attenuated in the Sibs group, reflecting reduced attention to speech changes. The P3a was found in all other groups.

Conclusions:  First, auditory processing was atypical in FXS, WS, and sibs. Second, the Sibs brain did not attach any importance to changes in speech sounds, whereas the DS, FXS, WS, and typically-developing brains did. These data are preliminary, but they hint at the identification of an early marker of autism, one that occurs as early as 14 months of age and is syndrome-specific.