ABSTRACT
CONTEXT: The basal ganglia and thalamus together connect in parallel closed-loop circuits with the cortex. Previous imaging studies have shown modifications of the basal ganglia and cortical targets in individuals with Tourette syndrome (TS), but less is known regarding the role of the thalamus in TS pathogenesis. OBJECTIVE: To study the morphological features of the thalamus in children and adults with TS. DESIGN: A cross-sectional, case-control study using anatomical magnetic resonance imaging. SETTING: University research center. PARTICIPANTS: The 283 participants included 149 with TS and 134 normal control individuals aged 6 to 63 years. MAIN OUTCOME MEASURES: Conventional volumes and measures of surface morphology of the thalamus. RESULTS: Analyses of conventional volumes and surface morphology were consistent in demonstrating an enlargement in TS-affected thalami. Overall volumes were 5% larger in the group composed of children and adults with TS. Statistical maps of surface contour demonstrated enlargement over the lateral thalamus. Post hoc testing indicated that differences in IQ, comorbid illnesses, and medication use did not account for these findings. CONCLUSIONS: Morphological abnormalities in the thalamus, together with the disturbances reported in the sensorimotor cortex, striatum, and globus pallidus, support the hypothesis of a circuitwide disorder within motor pathways in TS. The connectivity and function of the numerous and diverse thalamic nuclei within cortical-subcortical circuits constitute an anatomical crossroad wherein enlargement of motor nuclei may represent activity-dependent hypertrophy within this component of cortical-subcortical motor circuits, or an adaptive response within a larger putative compensatory system that could thereby directly modulate activity in motor circuits to attenuate the severity of tics.
Subject(s)
Thalamic Nuclei/pathology , Tourette Syndrome/pathology , Adult , Case-Control Studies , Cerebral Cortex/pathology , Child , Female , Humans , Hypertrophy/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Motor Cortex/pathology , Neural Pathways/pathology , Thalamus/pathologyABSTRACT
The C957T polymorphism in the dopamine D2 receptor (DRD2) gene and the Val158Met polymorphism in the Catechol-O-Methyl-Transferase (COMT) gene affect dopamine transmission and have been found to be associated with schizophrenia. Since DRD2 in mice and the COMT gene in humans modulate working memory, we examined the relationship and possible interaction of both polymorphisms to working memory performance in 188 healthy adults. Subjects having the DRD2 C/C allele showed the poorest performance in a word serial position test. Moreover, the effect of the C957T genotype was strengthened when interaction with the COMT Val158Met polymorphism was included in the analysis. We propose that an interaction of the DRD2 C957T and COMT Val158Met may be involved in the generation of some working memory deficits in schizophrenia.
