Tourette Disorder
Conditions
Keywords
Tourette, Serotonin, Impulsivity, Neuroimaging
Brief summary
Tourette disorder (TD) is a neurodevelopmental disorder characterized by motor and vocal tics. It is often associated with multiple psychiatric comorbidities involving a high degree of impulsivity such as obsessive-compulsive disorders (OCD), attention-deficit hyperactivity disorders (ADHD), and intermittent explosive disorders (IED). Although a substantial body of clinical studies have emphasized the role of the dopamine system in motor symptoms, little is known about how the serotonergic (5-HT) system modulate both cognitive and affective abilities in TD. Several lines of evidence suggest that different 5-HT receptor subtypes may constitute a crucial factor in the development and maintenance of different symptoms. Because abnormal 5-HT2A receptor bindings have been reported in patients with TD and aripiprazole (drug of first choice) is a 5-HT2A antagonist, we hypothesize that 5-HT2A receptors may play an important role in regulating psychiatric symptoms in TD such as those characterized by impulsive behaviors. To investigate the involvement of 5-HT2A receptors in TD, we propose to perform a multimodal imaging study with 20 adult patients (ON and OFF treatment). Neuroimaging data will be collected with a hybrid system that simultaneously combines the positron emission tomography (PET) and the functional magnetic resonance imaging (fMRI). A highly selective PET radiotracer (\[18F\]-altanserin) will map 5-HT2A receptor bindings in the whole brain, while fMRI will provide detail information regarding the altered brain activities.
Interventions
DRUGAdministration of a PET radiotracer
A highly selective 5-HT2A receptor ligand (\[18F\]-altanserin) will be injected to patients before each PET scan. The IV injection in the arm (via a catheter) will be performed in continue during a period of 2 hours in the imaging centre (CERMEP) before the acquisition. The dose will be 2,6 MBq/kg +/- 10 % depending the prescription of the nuclear medicine. Patients will be evaluated twice, one time free of neuroleptic treatment and a second time during stable chronic treatment by neuroleptic.
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion Criteria \* : * Male or Female * Diagnosed with a Tourette Disorder following the DSM-5 * Age between 18-65 years * Member of a social security scheme in France * Freely-given informed consent to participate to this study (written form) * With a current treatment by aripiprazole already scheduled * With Tics compatible with TEP/fMRI exams * Having (for women only) effective contraception throughout participation in the study.
Exclusion criteria
\* : * Male or Female * A serious not controlled psychiatric comorbidity * A serious, evolving or debilitating pathology with a potential influence on the study * Drug-taking with serotonergic effects (e.g., amphetamine, cocaine, MDMA, SSRIs, mianserin) * Contraindication for fMRI and PET (e.g., pacemaker, ferromagnetic implant, claustrophobia) * Women breastfeeding * Protected or restricted person (administratively or in judicial terms) * Participants to another study with radiations or radiotracers since less of one year, participants to a concomitant study * Do not speak french
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation coefficients between receptor-specific imaging data (PET) and scores of impulsivity measured by the Barratt scale (BIS11). | As the analysis requires a complex imaging processing, this outcome measure will be assessed in the year following the acquisition. | Correlation coefficients between changes in the binding potential (BPND) of \[18F\]-altanserin measured voxel-by-voxel in the whole brain and the evolution of scores BIS11 in TD patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation coefficients between receptor-specific imaging data (PET) and other clinical/behavioral scores. | As the analysis requires a complex imaging processing, this outcome measure will be assessed in the year following the acquisition. | Correlation coefficients between changes in the binding potential (BPND) of \[18F\]-altanserin measured voxel-by-voxel in the whole brain and the evolution of other clinical scores and task performance of TD patients. |
| Correlation coefficients between functional imaging data (fMRI) and scores of impulsivity measured by the Barratt scale (BIS11). | As the analysis requires a complex imaging processing, this outcome measure will be assessed in the year following the acquisition. | Correlation coefficients between changes in the BOLD signal measured voxel-by-voxel in the whole brain and the evolution of scores BIS11 in TD patients. |
| Correlation coefficients between functional imaging data (fMRI) and other clinical/behavioral scores. | As the analysis requires a complex imaging processing, this outcome measure will be assessed in the year following the acquisition. | Correlation coefficients between changes in the BOLD signal measured voxel-by-voxel in the whole brain and the evolution of other clinical scores and task performance of TD patients. |
Countries
France
Contacts
Primary ContactBenjamin PASQUEREAU
Backup ContactStephane THOBOIS
Outcome results
None listed