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| ID | Type | Description | Link |
|---|---|---|---|
| 1R21MH123870-01A1 | U.S. NIH Grant/Contract | View source | |
| 1R01MH113557-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This exploratory study seeks to examine M1 receptor availability in SZ patients and to relate M1 receptor availability to proximal and distal measures of cognitive performance, namely evoked ɣ oscillations in the EEG and verbal memory. Furthermore, the relationship between hippocampal [11C]EMO availability (BPND), evoked ɣ oscillations, verbal memory, and measures of illness severity will be explored.
Converging lines of evidence from postmortem studies provide strong evidence that brain muscarinic M1 receptor deficit is present in a subset of schizophrenia (SZ) patients. M1 receptors are an important target for cognitive deficits in SZ. However, until now, it has not been possible to examine the heterogeneity of SZ with respect to M1 receptor availability in vivo. The development of a novel positron emission tomography (PET) ligand, [11C]EMO, at Yale PET Center provides a unique opportunity to, for the first time, examine in vivo brain muscarinic M1 receptor availability in SZ and, concurrently, elucidate the relationship of M1 receptors to cognitive deficits in SZ.
The investigators will compare M1 receptor availability in SZ patients and age-, gender-matched healthy controls using [11C]EMO and the High Resolution Research Tomograph (HRRT), a PET scanner with high sensitivity and resolution available for human brain imaging. This study will explore the relationship between: hippocampal [11C]EMO binding (as a measure of hippocampal M1 AChR availability), encoding-related γ power during a verbal memory task, verbal memory, gender, and serum acetylcholine level. This exploratory study will provide the necessary pilot data to conduct a larger study to fully investigate the heterogeneity of SZ with respect to M1 receptor availability.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Schizophrenia or schizoaffective disorder | Experimental | Participants will undergo a single PET scan with [11C]EMO ≤ 20 mCi |
|
| Healthy Controls | Experimental | Participants will undergo a single PET scan with [11C]EMO ≤ 20 mCi |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor | Drug | The radiotracer, [11C]EMO, will be administered at the beginning of each PET scan. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Hippocampal M1 availability | Measured by [11C]EMO availability (BPND) | 10 days |
| Measure | Description | Time Frame |
|---|---|---|
| evoked ɣ oscillations | Measured by EEG | 10 days |
| verbal memory | Measured by cognitive assessments | 10 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rajiv Radhakrishnan, MD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Connecticut Mental Health Center | New Haven | Connecticut | 06519 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29643252 | Background | Mogg AJ, Eessalu T, Johnson M, Wright R, Sanger HE, Xiao H, Crabtree MG, Smith A, Colvin EM, Schober D, Gehlert D, Jesudason C, Goldsmith PJ, Johnson MP, Felder CC, Barth VN, Broad LM. In Vitro Pharmacological Characterization and In Vivo Validation of LSN3172176 a Novel M1 Selective Muscarinic Receptor Agonist Tracer Molecule for Positron Emission Tomography. J Pharmacol Exp Ther. 2018 Jun;365(3):602-613. doi: 10.1124/jpet.117.246454. Epub 2018 Apr 11. | |
| 15661360 |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Dec 5, 2024 | |
| Reset | Dec 26, 2024 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Dec 5, 2024 | Dec 26, 2024 |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D043643 | Receptor, Muscarinic M1 |
| D049268 | Positron-Emission Tomography |
| ID | Term |
|---|---|
| D011976 | Receptors, Muscarinic |
| D043562 | Receptors, G-Protein-Coupled |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
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Two groups will be studied: 1.) patients diagnosed with schizophrenia or schizoaffective disorder, and 2.) age and gender-matched healthy controls. Both groups will undergo neuroimaging, cognitive assessments, etc.
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| PET Scan | Device | PET scanner with high sensitivity and resolution available for human brain imaging |
|
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| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011950 | Receptors, Cholinergic |
| D017981 | Receptors, Neurotransmitter |
| D014055 | Tomography, Emission-Computed |
| D007090 | Image Interpretation, Computer-Assisted |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D007089 | Image Enhancement |
| D010781 | Photography |
| D011877 | Radionuclide Imaging |
| D014054 | Tomography |
| D003947 | Diagnostic Techniques, Radioisotope |