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| Name | Class |
|---|---|
| Weston Havens Foundation | UNKNOWN |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Control (HC) Participants | Experimental | Participants will undergo positron emission tomography-magnetic resonance (PET-MR) imaging using the [11C]UCB-J radiotracer |
|
| Schizophrenia (SZ) Participants | Experimental | Participants will undergo positron emission tomography-magnetic resonance (PET-MR) imaging using the [11C]UCB-J radiotracer |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [11C]UCB-J radiotracer | Drug | I.V. bolus administration of up to 15 mCi (equivalent to 0.3 rems) in the antecubital vein |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 120 minutes (scan duration) |
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Inclusion Criteria:
18 - 65 years in age
For SZ participants:
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:
For SZ participants:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Study Coordinator | Contact | 650-849-0552 | brain-research@stanford.edu |
| Name | Affiliation | Role |
|---|---|---|
| Jong H Yoon, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Palo Alto Health Care System | Recruiting | Palo Alto | California | 94304 | United States | |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26937191 | Background | Chong HY, Teoh SL, Wu DB, Kotirum S, Chiou CF, Chaiyakunapruk N. Global economic burden of schizophrenia: a systematic review. Neuropsychiatr Dis Treat. 2016 Feb 16;12:357-73. doi: 10.2147/NDT.S96649. eCollection 2016. | |
| 27440727 | Background | Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK, Dhaher R, Matuskey D, Baum E, Holden D, Spencer DD, Mercier J, Hannestad J, Huang Y, Carson RE. Imaging synaptic density in the living human brain. Sci Transl Med. 2016 Jul 20;8(348):348ra96. doi: 10.1126/scitranslmed.aaf6667. |
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No current plan to share data
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| PET-MR | Device | Positron emission tomography and magnetic resonance imaging, with a scan duration of up to 120 minutes |
|
| Stanford University |
| Recruiting |
| Stanford |
| California |
| 94305 |
| United States |
| 26814963 | Background | Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, Tooley K, Presumey J, Baum M, Van Doren V, Genovese G, Rose SA, Handsaker RE; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Daly MJ, Carroll MC, Stevens B, McCarroll SA. Schizophrenia risk from complex variation of complement component 4. Nature. 2016 Feb 11;530(7589):177-83. doi: 10.1038/nature16549. Epub 2016 Jan 27. |
| 26848175 | Background | Nabulsi NB, Mercier J, Holden D, Carre S, Najafzadeh S, Vandergeten MC, Lin SF, Deo A, Price N, Wood M, Lara-Jaime T, Montel F, Laruelle M, Carson RE, Hannestad J, Huang Y. Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain. J Nucl Med. 2016 May;57(5):777-84. doi: 10.2967/jnumed.115.168179. Epub 2016 Feb 4. |
| 7187776 | Background | Feinberg I. Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatr Res. 1982-1983;17(4):319-34. doi: 10.1016/0022-3956(82)90038-3. |
| 28792356 | Background | Finnema SJ, Nabulsi NB, Mercier J, Lin SF, Chen MK, Matuskey D, Gallezot JD, Henry S, Hannestad J, Huang Y, Carson RE. Kinetic evaluation and test-retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans. J Cereb Blood Flow Metab. 2018 Nov;38(11):2041-2052. doi: 10.1177/0271678X17724947. Epub 2017 Aug 9. |
| 30014145 | Background | Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurol. 2018 Oct 1;75(10):1215-1224. doi: 10.1001/jamaneurol.2018.1836. |
| 12468889 | Background | Wu Y, Carson RE. Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J Cereb Blood Flow Metab. 2002 Dec;22(12):1440-52. doi: 10.1097/01.WCB.0000033967.83623.34. |