CONCLUSION:
Eighty-five percent of subjects reported a reduction in tic symptoms during adolescence. Only increased tic severity in childhood was associated with increased tic severity at follow-up. The average age at worst-ever tic severity was 10.6 years. Forty-one percent of patients with TS reported at one time experiencing at least moderate OCD symptoms. Worst-ever OCD symptoms occurred approximately 2 years later than worst-ever tic symptoms. Increased childhood IQ was strongly associated with increased OCD severity at follow-up.

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CONCLUSION:
The findings in this study have important implications for understanding the developmental trajectory of brain functioning in persons with Tourette’s syndrome. Taken together with a large body of evidence from other Tourette’s syndrome imaging studies, our observations are consistent with the hypothesis that disturbances in the maturation of the frontostriatal systems that mediate self-regulatory control contribute to the development, persistence, and severity of tic symptoms. Frontostriatal disturbances may also contribute to the inability of individuals with Tourette’s syndrome to regulate default-mode brain activity during this attention-demanding task. Both the improvement in task performance with age and the greater activation of frontostriatal regions when individuals with Tourette’s syndrome are struggling with the task likely reflect compensatory responses to the presence of subtle functional disturbances in the efficiency of neural processing within frontostriatal regulatory circuits. Compensatory responses may serve to enhance self-regulatory control, thereby allowing individuals with Tourette’s syndrome to maintain task performance and, as indicated in a prior study of tic suppression (36), to regulate the severity of their tics.

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CONCLUSION:
These findings are consistent with the known plasticity of the dentate gyrus and with findings from previous imaging studies suggesting the presence of failed compensatory plasticity in adults with TS who have not experienced the usual decline in symptoms during adolescence.

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CONCLUSION:
Our results give further evidence that the genetics of Gilles de la Tourette syndrome is complex and suggest that Gilles de la Tourette syndrome is not a unitary condition, thus confirming the results of earlier studies which have described several Gilles de la Tourette syndrome phenotypes. Although a genome scan on the pedigree reported three areas of interest and the present study found three factors, further studies would have to be undertaken to elucidate whether the three factors ‘mapped’ with the genetic data. Possible reasons for our findings and suggestions for future research are discussed.

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