Testing the prenatal hormone hypothesis of tic-related disorders: Gender identity and gender role behavior

The hypothesis that prenatal masculinization of the brain increases risk of tic disorders in postnatal life was tested by measuring gender and gender role behavior in 89 children and adults with a clinical diagnosis of Tourette syndrome or obsessive compulsive disorder and 67 healthy, unaffected children and adults. Consistent with this hypothesis, a tic disorder in females was associated with more gender dysphoria, increased masculine play preferences, and a more typically “masculine” pattern of performance on two sex-typed spatial tasks. Males with tic disorders reported increased masculine play preferences, and the strength of these preferences was positively associated with the severity of tic symptoms. In addition, unlike their female counterparts, males with tic disorders showed a relative impairment in mental rotation ability. These behavioral profiles are consistent with those of children who have verifiable elevations in prenatal androgen levels. These findings therefore support the hypothesis that an altered androgen-dependent process of sexual differentiation during prenatal life may contribute to the development of tic-related disorders.This work was supported by National Institutes of Health Grants MH01232 (B. P.) and MH59139 (B. P.) and the Suzanne Crosby Murphy endowment in Pediatric Neuropsychiatry, College of Physicians and Surgeons, Columbia University. The authors thank Amy Basile and Shibani Mukerji for their valuable assistance with behavioral testing.