Neural Structure and Function in Tourette Syndrome: distinguishing neural structure and function in Tourette Syndrome from attention-deficit/hyperactivity disorder.

Tourette Syndrome (TS) is a common neuropsychiatric disorder amongst children
and adolescents. Attentio-Deficit/Hyperactivity Disorder (ADHD) is often found
comorbid with TS, similarly tic disorders often comprise secondary diagnoses in
ADHD, making it difficult to eliminate the potential confounds of comorbidity
on research findings in TS. Though the frontostriatal circuits and its main
regions, the prefrontal cortex and the basal ganglia have been implicated in
TS, there are multiple inconsistent findings in studies on structural and
functional MRI measures and executive functioning in TS. Glutamate is a major
neurotransmitter modulating the activity of the frontostriatal circuits, but
its role in TS in unclear.

The aim of the study is to acquire MRI, genetic and neuropsychological data on
TS subjects. We aim to do this for the purpose of then identifying brain (1)
structural, (2) functional and (3) connectivity abnormality differences, and
(4) neuropsychological data between subjects with TS, healthy controls, and
ADHD to elucidate which neural correlates correspond to each condition, which
are common and which unique. Finally (5) glutamate concentrations from the
frontostriatal region, acquired with magnetic resonance spectroscopy (MRS),
will be compared between healthy controls and ADHD. Secundary exploratory
objectives are: identify genetic mechanisms underlying compulsive behaviours in
high risk subjects and controls, and identify biomarkers for the compulsivity
trait.

Longitudinal case control study with three groups; (1) TS, (2) ADHD and (3)
healthy controls. Participants will be assessed at baseline and again in a
similar manner about 3 years after the initial assessment.

The burden involves taking part in an MRI scan and having blood drawn once at
baseline and once at follow-up three years later. Participants will undergo an
hour scanning session in the MRI scanner. The session will be divided into two
separate days. There may be some discomfort experienced due to the loud noise
of the MRI and being confined to a small space within the bore of the MRI
instrument. Furthermore, there may be some discomfort for the patients in
recalling psychiatric symptoms and during blood draw. Degree of anxiety and
degree of pleasure will be permanently monitored and explicitly asked of
parents and children. If children show any resistance the procedure will be
stopped immediately.

Risks and physical or physiological discomfort will be negligible and no
special risks are associated with this kind of research. Participation in the
study will be of no direct therapeutic benefit to individual patients, however,
the study will benefit the population at large, possibly helping future
patients with tic disorders. The anticipated scientific merits justify the
proposed study.
This research protocol includes the participation of minors. Tic disorders have
a childhood onset and often lessen in intensity and frequency or may even
disappear during adulthood. The study's goals can only be achieved by studying
children as these patterns of behaviour are developing over early adolescence.