Genetic association signal near NTN4 in Tourette syndrome.

Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10(-3) ) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry-matched controls. Only rs2060546 on chromosome 12q22 (p = 3.3 × 10(-4) ) remained significant after Bonferroni correction. Meta-analysis with the original GWAS yielded the strongest association to date (p = 5.8 × 10(-7) ). Although its functional significance is unclear, rs2060546 lies closest to NTN4, an axon guidance molecule expressed in developing striatum. Risk score analysis significantly predicted case-control status (p = 0.042), suggesting that many of these variants are true TS risk alleles.

A multicenter randomized placebo-controlled clinical trial of pramipexole for Tourette's syndrome.

BACKGROUND: Dopamine agonists could theoretically normalize the suspected central dopamine hypersensitivity in Tourette's syndrome. METHODS: There was a multicenter randomized, placebo-controlled, double-blind clinical trial of pramipexole given for 6 weeks in 63 children and adolescents with Tourette's syndrome. RESULTS: There were no significant differences in the adjusted mean change in the Total Tic Score of the Yale Global Tic Severity Scale for patients treated with pramipexole (-7.16) and placebo (-7.17). There were no significant treatment effects on change from baseline in the Global Severity score of the Yale Scale and parent- and investigator-scored Clinical Global Impression of Improvement. In patients with attention deficit hyperactivity disorder, there was improvement in DuPaul ADHD scale scores for patients receiving pramipexole compared with placebo. CONCLUSIONS: There was no evidence that pramipexole has efficacy in suppressing tics. Pramipexole may decrease symptoms of associated attention deficit hyperactivity disorder.