A preliminary study of tryptophan depletion on tics, obsessive-compulsive symptoms, and mood in Tourette's syndrome

Tourette's syndrome (TS) is a chronic neuropsychiatric disorder of childhood onset characterized by motor and phonic tics that wax and wane in severity, as well as by symptoms of obsessive-compulsive disorder (OCD) (Pauls and Leckman 1986; Leckman et a1 1992). There have been conflicting reports regarding altered tryptophan (TRP) metabolism and abnormalities in the serotonin (5-HT) system in TS. In one study of 7 TS subjects and 10 normal controls, no group differences in whole blood TRP were seen (Dursun et a1 1994); however, in two larger studies, whole blood TRP was lower in the TS group (Leckman et a1 1984; Comings 1990). Cerebrospinal fluid (CSF) levels of TRP have also been reported to be slightly but nonsignificantly lower in TS subjects, while within the TS group, CSF TRP was inversely related to tic severity (Leckman et a1 1995). Finally, a postmortem study found lower TS group mean levels of 5-HT and 5-hydroxy indoleacetic acid (5-HIAA), the major metabolite of 5-HT, in nearly all subcortical brain regions examined (Anderson et a1 1992). A role for altered TRP metabolism or underactivity of the brain 5-HT system in the pathophysiology of TS is also suggested by the emergence of transient motor tics in a patient with OCD participating in an acute TRP depletion study (Goodman WK, personal communication). In addition, there is a report of the successful treatment of stimulant-induced tics with oral TRP (Chandler et a1 1989). We therefore elected to systematically study the effects of acute TRP depletion in a group of subjects with TS.