Gray Matter Volume Deficit and Neuropsychological Performance in First Degree Relatives of Children with Autism Spectrum Disorder

Background:  

Neurobiological studies evaluating for potential endophenotypic markers in First Degree Relatives (FDRs) of children with Autism Spectrum Disorder (ASD) are sparse in India because a) very few centers in the country are involved in research of this kind, b) challenges of obtaining consent from participating parents. Search for endophenotypic markers in ASD, a known to be a heritable disorder, is a logical way forward. Among several neurocognitive parameters, facial emotion recognition deficit is one such marker. However, concurrent assessment involving both neuropsychological tests and gray matter volumes in FDRs of ASD has received little attention.

Objectives:  

To study the gray matter volume and the neuropsychological profile of FDRs of children with ASD

Methods:  

36 parent/s of 19 children with ASD and 11 matched controls were recruited for the study in a university teaching hospital in southern India. The index children aged 30 months to 14 years were diagnosed by experienced child psychiatrists as per DSM IV guidelines. The index children were rated on Childhood Autism Rating Scale (CARS). Parents were assessed using a) MINI-Plus, b) neuropsychological assessment that comprised tests from the NIMHANS Neuropsychological battery, subtests of Wechsler’s memory scale III and the Embedded figure test, c) Magnetic Resonance Imaging (3-Tesla):T1-weighted images were processed using SPM (http://www.fil.ion.ucl.ac.uk/spm), implemented through the Voxel Based Morphometry (VBM) Toolbox 8. Statistical parametric maps were examined for group differences as well as correlation between Gray Matter Volumes (GMV) of FDRs and CARS scores of the index child / neuropsychological test scores of FDRs.

Results:  

There was a significant negative correlation between the CARS score of the index child and left superior parietal lobule [T=5.76] and right insula [T=5.58] GMV of the FDRs (N=36).  The FDRs  had significantly deficient volume of right fusiform gyrus in comparison with healthy controls [T=3.45]. FDRs (N=31) demonstrated a significant negative correlation between a) the embedded figure test score and bilateral superior temporal gyri [Left: T=5.71; Right: T=5.31], b) finger-tapping test score and left inferior frontal gyrus [T=5.89] c) Controlled Word Association Task score and the left middle frontal gyrus [N=29; T=4.22]. All these findings were significant at p (uncorrected) ≤ 0.001 and small volume correction (p<0.05).

Conclusions:  

Certain brain regions implicated in the study findings are relevant for neurocognitive aberrations seen in ASD, namely, fusiform gyrus in face processing and fronto-temporal network in working memory.  Significant negative correlation between neuropsychological test performance and frontal/temporal brain regions in this study adds support to what is already stated in literature. The findings of the Superior Parietal Lobule (which has been implicated in mediating motor learning and repetitive behavior) and the Insula (implicated in emotion processing) having a negative correlation with the CARS score needs further confirmation.  Larger sample of FDRs, improved methods and addition of oculomotor tests of sensorimotor responses and diffusion tensor imaging studies may give us more robust support for these findings and potentially reveal additional endophenotypic markers for ASD.