The identification of the neurobiological bases of Tourette syndrome (TS) is critical to allow for the development of effective strategies for the prevention and therapy of this disorder. Ample evidence indicates that: 1) TS is a heritable disorder; 2) early exposure to stress may be a TS risk factor; 3) the prevalence in males is four-fold higher than in females. This background suggests that TS may be caused by complex interactions of genetic, environmental and sex-related factors. The preliminary evidence collected by our group over the past few years suggests that these interactions may be modulated by the enzyme 5?-reductase type 2 (5AR2), which catalyzes the rate-limiting step in the conversion of testosterone into androgenic neuroactive steroids (NS). Indeed, NS have been shown to play a key role in the orchestration of stress response and gender differences in behavior. Furthermore, in a preliminary open trial, we found that the 5AR2 inhibitor finasteride significantly reduced tic severity in adult male TS patients. To verify whether 5AR2 play a role in the pathogenesis of TS, we will study whether male TS patients feature a significant association of specific polymorphic variants of its gene (SRD5A2) and early stress and/or trauma, in comparison with non-affected controls. In addition, in a separate group of male TS patients under finasteride treatment, we will study whether the amelioration in tic and symptom severity induced by this drug is correlated with specific changes in NS profiles. The results of these studies will help us elucidate the genetic and molecular bases of the male predominance and stress sensitivity in TS, and ultimately provide important leads for the prevention and therapy of this disorder. Marco Bortolato, M.D., Ph.D., Michele T. Pato, M.D. & Jeremiah M. Scharf, M.D., Ph.D. University of Kansas, Lawrence, KS Award: $149,998 Tourette Association of America Inc. – Research Grant Award 2013-2014
Role of 5-Alpha Reductase 2 and Androgens in Tourette Syndrome
Grant Type
Clinical
Grant Year
2013-2014
Institution Location
KS
Institution Organization Name
University of Kansas, Lawrence, KS
Investigators Name
Bortolato, Marco, MD, PhD