Distinct structural changes underpin clinical phenotypes in patients with Gilles de la Tourette syndrome

Yulia Worbe, Emilie Gerardin, Andreas Hartmann, Romain Valabrégue, Marie Chupin, Léon Tremblay, Marie Vidailhet, Olivier Colliot, Stéphane Lehéricy
Brain 2010, 133: 3649-60
Gilles de la Tourette syndrome is a childhood-onset neurodevelopmental disorder characterized by tics that are often associated with psychiatric co-morbidities. The clinical heterogeneity of Gilles de la Tourette syndrome has been attributed to the disturbance of functionally distinct cortico-striato-thalamo-cortical circuits, but this remains to be demonstrated. The aim of this study was to determine the structural correlates of the diversity of symptoms observed in Gilles de la Tourette syndrome. We examined 60 adult patients and 30 age- and gender-matched control subjects using cortical thickness measurement and 3 T high-resolution T(1)-weighted images. Patients were divided into three clinical subgroups: (i) simple tics; (ii) simple and complex tics and (iii) tics with associated obsessive-compulsive disorders. Patients with Gilles de la Tourette syndrome had reduced cortical thickness in motor, premotor, prefrontal and lateral orbito-frontal cortical areas. The severity of tics was assessed using the Yale Global Tic Severity Scale and correlated negatively with cortical thinning in these regions, as well as in parietal and temporal cortices. The pattern of cortical thinning differed among the clinical subgroups of patients. In patients with simple tics, cortical thinning was mostly found in primary motor regions. In patients with simple and complex tics, thinning extended into larger premotor, prefrontal and parietal regions. In patients with associated obsessive-compulsive disorders, there was a trend for reduced cortical thickness in the anterior cingulate cortex and hippocampal morphology was altered. In this clinical subgroup, scores on the Yale-Brown Obsessive-Compulsive Scale correlated negatively with cortical thickness in the anterior cingulate cortex and positively in medial premotor regions. These data support the hypothesis that different symptom dimensions in Gilles de la Tourette syndrome are associated with dysfunction of distinct cortical areas and have clear implications for the current neuroanatomical model of this syndrome.

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