Cortical Thickness and ASD in 22q11.2 Deletion Syndrome; An International Collaboration

Friday, May 12, 2017: 12:00 PM-1:40 PM
Golden Gate Ballroom (Marriott Marquis Hotel)
M. Gudbrandsen1,2, E. Daly2, C. M. Murphy2, L. Kushan3, D. Sun3, D. G. Murphy2, C. Ecker4, C. Bearden3 and M. C. Craig5, (1)The Sackler Institute for Translational Neurodevelopmental Sciences, IoPPN, King's College London, London, United Kingdom, (2)Department of Forensic and Neurodevelopmental Sciences, and the Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom, (3)Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, (4)Department of Child and Adolescent Psychiatry, Psychosomatics and Psychiatry, Goethe-University Frankfurt am Main, Frankfurt, Germany, (5)IoPPN, London, UNITED KINGDOM
Background: Individuals with syndromic forms of autism spectrum disorder (ASD) provide a unique opportunity to understand specific genetic risk mechanisms. For example, individuals with 22q11.2 Deletion Syndrome (22q11DS) are at significant risk (30–50%) of developing ASD (Schneider et al., 2014). The neurobiological mechanisms contributing to this increased risk are unknown – but likely include genetically determined differences in particular developmental pathways. We and others previously reported that individuals with ASD have significant differences in cortical thickness (CT) (e.g. (Ecker et al., 2013). CT is important because it results from distinct neurodevelopmental pathways and is a proxy measure of dendritic arborization and pruning.

Objectives: We wished to establish whether variation in CT is associated with comorbid ASD in 22q11DS individuals.

Methods: We included 73 individuals with 22q11DS (23 males and 34 females), aged between 6 and 33 years (mean age=14, SD=6). Of these, 36 individuals met diagnostic criteria for ASD based on the ADI-R & ADOS. The resulting two groups (i.e. 22q11DS+ASD & 22q11DS-ASD) did not differ significantly on age or IQ. Participants underwent structural T1-weighted magnetic resonance imaging (MRI) at the Institute of Psychiatry, Psychology and Neuroscience, London & The Semel Institute for Neuroscience, UCLA. CT was measured using FreeSurfer (http://surfer.nmr.mgh.harvard.edu). Vertex-wise statistical analysis of CT measures were estimated by regression of a GLM including group as categorical fixed effect factor. A random-field-based cluster-threshold (p<0.05) was applied to correct for multiple comparisons (Worsley 1999).

Results: Individuals with 22q11DS+ASD, when compared to 22q11DS-ASD, had significantly increased cortical grey matter thickness in 2 right hemisphere brain areas; the inferior frontal gyrus (BA47) & postcentral gyrus (BA43)(Fig. 1).

Conclusions: This is the first known study to indicate that absence or presence of comorbid ASD is associated with genetically determined variation in cortical morphometry. Future research is required to determine how genetic variation within the deleted region determines outcome.