Face Processing as An Endophenotype for the ASD Population

Background: In an attempt to identify genes that contribute to different aspects of the autism spectrum disorder (ASD) phenotype, we examined an endophenotype of ASD and correlated this with specific gene variants, particularly functional variants that impact the outcome of two relevant biochemical pathways.  Face processing – the process of perception, reaction and recognition that the brain goes through when it perceives a visual stimulus that is configured like a face – is both a social and communicative behaviour that appears early in development, and is linked with many early milestones.  Converging evidence from brain imaging studies, event related brain potentials and eye-tracking indicates that the physiological responses that are associated with face processing in typically developing individuals are atypical in individuals with ASD.  Furthermore, there is a relationship between abnormalities in face processing in subclinical autism spectrum traits (thought to be present in those genetically related to those with ASD) and those who actually have an autism spectrum condition which indicates that this trait may be a genetically determined marker for ASD.  Thus we identified face processing abnormalities as an endophenotype of ASD. 

Objectives: This electroencephalogram study addresses the question of whether the relevant polymorphisms of either of the candidate genes (COMT and 5-HTTLPR) that are associated with behavioural effects in response to the viewing of the human face (changes to the N170 and N400 event-related potentials) occur more or less frequently in the autism spectrum disorder (ASD) population and in their first-degree relatives.  Given the association of variants in the COMT and 5HTTLPR genes with latency and amplitude of the N170 and N400 waveforms, respectively, it is hypothesized that there is an increased frequency of COMT158Val allele and 5HTTLPR short allele in individuals with ASD and that these variants are associated with poor face processing (i.e. increased N170 latency and reduced N400 amplitude.)

Methods: For genetic assays, a non-invasive saliva or cheek swab sample is collected from each individual with ASD and any consenting first-degree relatives as well as from any unaffected and unrelated age- and gender-matched control participants.  A 128-channel EEG is recorded while the participant is asked to look at both faces and objects that appear on the computer screen.  The stimuli consist of one face (which elicits the N170 waveform), presented with three expressions: joy, anger, neutrality (which elicits the N400 waveform).  There are also three photos of objects.  Each face and each object is displayed twenty times for 1300 milliseconds (ms) each time, in a random order, with 1200-1600 ms of black screen between each stimulus presentation.

Results: These data comprise an evolving dataset rendering conclusions preliminary.  Individuals with ASD and their first-degree relatives show atypical face processing relative to controls.  Genetic correlations are modest; a larger sample is required for more complete analysis.

Conclusions: The study of face processing as an endophenotype in this small sample of the ASD population and their first-degree relatives is fruitful and continues to be pursued.  Atypical face processing is present in these samples and a related genotype is hypothesized.