Schizophrenia
Conditions
Brief summary
The purpose of this study is to utilize the radioactive positron emission tomography (PET) tracer \[11C\]UCB-J to test the neural synaptic pruning hypothesis of schizophrenia. This imaging method allows for the quantification of synaptic density in the living human brain and has the unprecedented ability to directly examine the synaptic pathology underlying neuropsychiatric disease. The neural synaptic pruning hypothesis posits that a key pathogenic process of schizophrenia is the over-exuberant elimination of neural synapses during development. The confirmation of reduced synaptic density in schizophrenia as evidenced by \[11C\]UCB-J has the potential to lead to a number of ground-breaking clinical innovations, such as laboratory-based diagnostics and prognostics, and novel, disease-modifying treatments.
Interventions
I.V. bolus administration of up to 15 mCi (equivalent to 0.3 rems) in the antecubital vein
DEVICEPET-MR
Positron emission tomography and magnetic resonance imaging, with a scan duration of up to 120 minutes
Sponsors
Weston Havens Foundation
Davidzon, Guido, M.D.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 18 - 65 years in age * For SZ participants: * On a stable medication regimen for at least two weeks prior to testing * A clinical diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder * Able to complete a PET-MR scan without the use of sedation
Exclusion criteria
* Active substance use within three months of testing * IQ \< 70 * Major medical neurological illness or significant head trauma * Pregnancy or breastfeeding * Contraindication to MR scanning, including magnetic-resonance incompatible metal or hardware including pacemakers, cochlear implants, and bullets near a critical organ * Weight \> 350 lbs or a large body habitus that MR scanner cannot accommodate * History of or current claustrophobia * Inability to comply with basic study requirements such as following directions and punctuality * For HC participants: * Presence of a first degree relative with a psychotic disorder * Lifetime diagnosis of major psychiatric illness * For SZ participants: * Unstable psychiatric symptoms at the time of testing, e.g. acute suicidality, prominent psychosis, or behavioral dyscontrol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cross-sectional differences in synaptic density between HC and SZ participants | 120 minutes (scan duration) | Synaptic density will be quantified with the regional binding potential (BP\_ND), a measure of \[11C\]UCB-J binding. BP\_ND will be derived by using the simplified reference tissue model 2 (Wu & Carson, 2002) and the centrum semiovale as the reference region. This method has been recently utilized by other investigators in neuropsychiatric samples (Chen et al., 2018). Both exploratory voxel-wise BP\_ND and region of interest (ROI) BP\_ND will be compared across groups. ROIs include the striatum, dorsolateral prefrontal cortex, hippocampus, and superior temporal cortex. |
Countries
United States
Contacts
Primary ContactStudy Coordinator
Outcome results
None listed