Abnormal brain tryptophan metabolism and clinical correlates in Tourette syndrome

Authors

  • Michael Behen PhD,

    1. Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
    2. Department of Neurology, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
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  • Harry T. Chugani MD,

    Corresponding author
    1. Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
    2. Department of Neurology, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
    3. Department of Radiology, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
    • Pediatric Neurology/PET Center, Children's Hospital of Michigan, 3901 Beaubien Blvd., Detroit, MI 48201, USA
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  • Csaba Juhász MD, PhD,

    1. Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
    2. Department of Neurology, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
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  • Emily Helder MA,

    1. Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
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  • Albert Ho BS,

    1. Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
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  • Mohsin Maqbool MD,

    1. Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
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  • Robert D. Rothermel PhD,

    1. Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
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  • Jacquie Perry BA,

    1. Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
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  • Otto Muzik PhD

    1. Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
    2. Department of Radiology, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan
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Abstract

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 α-[11C]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. © 2007 Movement Disorder Society

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