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 disturbances and their relationship to clinical phenotype remains poor. We used alpha-[(11)C]methyl-L-tryptophan (AMT) positron emission tomography (PET) to assess global and focal brain abnormalities of tryptophan metabolism and their relationship to behavioral phenotype in 26 children with TS and nine controls. Group comparisons on regional cortical and subcortical AMT uptake revealed decreased AMT uptake in bilateral dorsolateral prefrontal cortical and bilaterally increased uptake in the thalamus (P = 0.001) in TS children. The ratio of AMT uptake in subcortical structures to dorsolateral prefrontal cortex was significantly increased bilaterally (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 abnormalities of tryptophan metabolism in TS and provides neuroimaging evidence for a role of serotonergic mechanisms in the pathophysiology of TS.
Behen
Michael
M
Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Chugani
Harry T
HT
Juhász
Csaba
C
Helder
Emily
E
Ho
Albert
A
Maqbool
Mohsin
M
Rothermel
Robert D
RD
Perry
Jacquie
J
Muzik
Otto
O
D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D012701:Serotonin / Q000378:metabolism; D012720:Severity of Illness Index; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism; D005879:Tourette Syndrome / Q000000981:diagnostic imaging* / Q000378:metabolism*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D012701:Serotonin; C028129:tryptophan methyl ester; D014364:Tryptophan