About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
18 - 65 years in age
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
Disqualifiers
Active substance use within three months of testing
IQ < 70
Major medical neurological illness or significant head trauma
Pregnancy or breastfeeding
Trial design
Parallel
Treatments tested in this trial
[11C]UCB-J radiotracer
DrugI.V. bolus administration of up to 15 mCi (equivalent to 0.3 rems) in the antecubital vein
PET-MR
DevicePositron emission tomography and magnetic resonance imaging, with a scan duration of up to 120 minutes
Treatment groups
Trial outcomes
Primary outcomes
Cross-sectional differences in synaptic density between HC and SZ participants
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.
Sponsors and contacts
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Davidzon, Guido, M.D.
Lead sponsor
Stanford University
Sponsor institution
Weston Havens Foundation
Collaborator