EXON AND INTRON VARIANTS IN THE HUMAN TRYPTOPHAN 2,3-DIOXYGENASE GENE- POTENTIAL ASSOCIATION WITH TOURETTE SYNDROME, SUBSTANCE-ABUSE AND OTHER DISORDERS

Defects in serotonin metabolism, and abnormalities in both blood serot onin and tryptophan levels, have been reported in many psychiatric dis orders, Tryptophan 2,3-dioxygenase (TDO2) is the rate limiting enzyme for the breakdown of tryptophan to N-formyl kenurenine, Functional var iants of this gene could account for the observed simultaneous increas es or decreases of both serotonin and tryptophan in various disorders, We have identified four different polymorphisms of the human TDO2 gen e, Association studies show a significant association of one or more o f these polymorphisms and Tourette syndrome (TS), attention deficit hy peractivity disorder (ADHD) and drug dependence, The intron 6(G-->T) v ariant was significantly associated with platelet serotonin levels, On ly the association with TS was significant with a Bonferroni correctio n (p=0.005), Our purpose here is not to claim these associations are p roven, but rather to report preliminary results and show that easily t estable polymorphisms are available, We hope to encourage additional r esearch into the potential role the TDO2 gene in these and other psych iatric disorders.