Thinning of the Motor–Cingulate–Insular Cortices in Siblings Concordant for Tourette Syndrome

Abstract

Fraternal twin studies on normal subjects have demonstrated low heritability (intra-class correlation coefficient) estimates for frontal brain regions (r = 0.43). Here we aimed to investigate the relatedness/similarity estimates of the frontal brain regions in fraternal subjects concordant for Tourette syndrome (TS). We sought to identify regional brain similarities between siblings concordant for TS as an exploratory step towards the identification of potential brain structures involved in the TS phenotype. The identified brain structures may then serve in subsequent molecular genetic and linkage studies. In addition, we regressed cortical thickness and TS clinical severity scores to assess the relation between TS clinical symptoms and cortical structures. Sixteen sibling pairs concordant for TS were scanned using a 1.5 T magnetic resonance imaging scanner (age range 10-25, mean 17.19 +/- 4.1). Brain morphology was assessed using the fully automated Civet pipeline at the Montreal Neurological Institute. TS was assessed using the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS) and the Goetz Tic Scale. We report high relatedness/similarity estimates for fraternal siblings concordant for TS (r = 0.86-0.60) in the middle frontal-motor/cingulate/insular cortices. Regression analysis revealed significant negative correlations in the right insula with the YGTSS (r = -0.41, F = 6.09, P < 0.02) and the left cingulated cortex with the (CY-BOCS) (r = -0.35, F = 4.30, P < 0.05). Since previous findings have concluded that normal fraternal siblings are less alike in frontal cortices, the present findings may be attributed to TS. We speculate that the high ICC between siblings and the negative correlation between TS symptoms severity and cortical thickness measurements are related to the disturbances in the maturation of the motor-cingulate-insular cortical neural system that mediate self-regulatory processes. Such delayed maturation may consequently contribute to the development of TS by releasing motor and vocal tics from regulatory control. These findings may have important genetic implications.