Several lines of evidence implicate dopamine (DA) neuronal systems in the pathogenesis of Tourette's syndrome (TS). Clinically, tics and related repetitive behaviors are exacerbated by pharmacological agents which enhance synaptic DA function (e.g., psychostimulants)k, while medications which reduce DA neurotransmission (e.g., synthesis/storage inhibitors and neuroleptic medications) ameliorate TS symptoms. In addition, neurochemical studies in TS patients have demonstrated change in cerebrospinal fluid indices of DA metabolism. While the precise neuroanatomical correlates of these phenomena are unknown, the involvement of DA projections to the basal ganglia in other movement disorders (e.g., Parkinson's disease and tardive dyskinesia, including tardive tic disorder) has focused attention on subcortical DA circuits in TS. In a recent post-mortem study, Singer et al. (61) reported significant elevations in [3H]mazindol binding, a marker of striatal DA transporters, in patients with TS as compared to control samples. Specific binding was increased by 37% in the caudate and by 50% in the putamen, a finding which the authors interpret as indicating hyperinnervation of the basal ganglia in TS patients. We have developed a promising probe of the DA transporter, [123I]beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane), which can be safely used to quantify the levels of DA transporters in the living human brain with SPECT (single photon emission computed tomography). Previous work by our group has demonstrated its utility as a marker for the loss of striatal DA transporters seen with nigrostriatal degeneration in idiopathic Parkisnon's disease (29). The focus of the current proposal is to rigorously test the hypothesis that TS subjects have elevations in striatal DA transporters compared to healthy subjects. Our preliminary findings are consistent with this hypothesis and show a 38% elevation in striatal DA transporter levels in 5 TS subjects as compared to 5 age- and gender-matched healthy controls.) If confirmed in a larger study population, [123I]beta-CIT may prove to be a useful marker for elucidating the neurochemical correlates of behaviors associated with TS and other tic-spectrum disorders.
