Functional MRI Endophenotypes of Autism

Thursday, May 17, 2012
Sheraton Hall (Sheraton Centre Toronto)
10:00 AM
M. D. Spencer1, R. J. Holt1, L. R. Chura1, J. Suckling2, A. J. Calder3, E. T. Bullmore4 and S. Baron-Cohen1, (1)Department of Psychiatry, Autism Research Centre, University of Cambridge, Cambridge, United Kingdom, (2)Brain Mapping Unit, University of Cambridge, Cambridge, United Kingdom, (3)MRC Cognition and Brain Sciences Unit, Cambridge, United Kingdom, (4)Department of Psychiatry, Brain Mapping Unit, University of Cambridge, Cambridge, United Kingdom
Background:  Siblings of individuals with autism have over 20 times the population risk of autism. Evidence of comparable, but less marked, cognitive and social communication deficits in siblings suggests a role for these traits in the search for biomarkers of familial risk. However, no neuroimaging biomarkers of familial risk have been identified to date.

Objectives:  We aimed to examine functional magnetic resonance imaging (fMRI) data from teenagers with autism (n=40), their unaffected siblings (n=40) and controls with no family history of autism (n=40), to identify candidate biomarkers of familial risk for autism.  We aimed to contrast the three groups in order to separate fMRI abnormalities associated with autism itself as compared to those associated with the familial risk for autism in the broader phenotype.

Methods:  All participants with autism were assessed as positive on the Autism Diagnostic Observation Schedule - Generic and the Autism Diagnostic Interview - Revised.  All participants were aged 12-18 years, with IQ≥70. All participants were scanned on the same 3T unit and completed fMRI tasks including an implicit facial emotion processing task using emotional faces from a standard battery.

Results:  We found that the neural response to facial expression of emotion differs between unaffected siblings and controls with no family history of autism. Strikingly, the fMRI response to happy versus neutral faces was significantly reduced in unaffected siblings compared with controls within a number of brain areas implicated in empathy and face processing, including the right (p=0.002) and left (p=0.005) temporal poles and the right middle (p=0.004) and left posterior (p=0.016) superior temporal sulci. The response in unaffected siblings did not differ significantly from the response in autism. 

Conclusions:  These findings suggest that an atypical implicit response to facial expression of emotion may form the basis of impaired emotional reactivity in autism and in the broader autism phenotype in relatives. These results indicate that the fMRI response to facial expression of emotion is a marker of familial risk for autism and a functional neuroimaging endophenotype for autism, and may offer far-reaching insights into the etiology of autism.

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