Abnormal brain tryptophan metabolism and clinical correlates in Tourette syndrome

Symptoms in Tourette syndrome (TS) are likely related to abnormalities involving multiple neurotransmitter systems in striatal-thalamo-cortical circuitry. Although prior studies have found abnormal levels of tryptophan, serotonin, and their metabolites in blood, cerebrospinal fluid and brain tissue of TS patients, understanding of focal brain distur- bances and their relationship to clinical phenotype remains poor. We used -( 11 C)methyl-L-tryptophan (AMT) positron emission tomography (PET) to assess global and focal brain abnormalities of tryptophan metabolism and their relation- ship to behavioral phenotype in 26 children with TS and nine controls. Group comparisons on regional cortical and sub- cortical AMT uptake revealed decreased AMT uptake in bilateral dorsolateral prefrontal cortical and bilaterally in- creased uptake in the thalamus (P 0.001) in TS children. The ratio of AMT uptake in subcortical structures to dorso- lateral prefrontal cortex was significantly increased bilater- ally (P 0.01) in TS patients also. Behaviorally defined subgroups within the TS sample revealed differences in the pattern of AMT uptake in the fronto-striatal-thalamic circuit. This study demonstrates cortical and subcortical abnormal- ities of tryptophan metabolism in TS and provides neuroim- aging evidence for a role of serotonergic mechanisms in the pathophysiology of TS. © 2007 Movement Disorder Society