TS-EUROTRAIN - Projects

Glutamate metabolism in children, adolescents and adults with TS: a single voxel Magnetic Resonance Spectroscopy study (WP3)

Objectives: 1. Investigate levels of glutamate and its metabolites in TS patients compared to normal controls. 2. Investigate whether concentrations of glutamate metabolites are correlated to tic severity or to the existence and severity of comorbidities (ADHD and OCD). 3. Investigate whether brain’s glutamate metabolism is influenced by medication with aripiprazole. 4. Investigate whether treatment response to aripiprazole correlates to changes in the concentration of glutamate metabolites.

Fellow ESR12
Host institution: Hannover Medical School
Duration: 36 months    
Supervisor: K. Müller-Vahl, MHH; Co-supervisor: B. Mohammadi, INI (Associated partner). Seconding company: BI PHARMA.

Tasks and methodology: Although several lines of evidence suggest that glutamate might be involved in the pathophysiology of TS, there is only one in vivo MRS study available investigating brain’s metabolism (deVito 2005). In a group of 25 boys with TS, several reduced levels of metabolites were found in areas of the cortico-striatal-thalamo-cortical (CSTC) circuit. We hypothesize (1) that concentrations of glutamate metabolites will be different in patients with TS compared to age- and gender-matched normal controls, (2) that alterations in concentrations will correlate with disease severity and the existence and severity of comorbidities, and (3) that levels of glutamate metabolites might be used as biomarkers for the disease or treatment response.

  • Task 1: In collaboration with the Associated Partner at the INI, we will use MRS to investigate whole brain and regional levels of N-acetyl compounds (NA), total creatine (tCR), choline-containing compounds (CHO), myo-inositol (MI), and glutamate+glutamine (GLX) in different brain regions (including the basal ganglia, frontal cortex regions, thalamus, amygdale, anterior cingulated cortex) that has been suggested to be pathophysiologically involved in TS.
  • Task 2: Glutamate metabolism will be investigated in 25 unmedicated patients with TS compared to age- and gender-matched healthy controls (n=25).
  • Task 3: Glutamate metabolism will be reinvestigated for a second time in the same group of 25 TS patients during treatment with the antipsychotic drug aripiprazole (treatment duration > 2 months).
  • Task 4: Concentrations of glutamate and its metabolites will be correlated to tic severity, severity of ADHD, OCD, and depression, and treatment response.

Milestones: 1. Recruitment and clinical assessment of patients 2. First MRS (pretreatment) 3. Treatment 4. Second MRS (during treatment)

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