This study is designed to examine SV2A density in MDD and PTSD as a correlate of synaptic density, and to determine whether ketamine administration will reverse the synaptic loss in vivo in human subjects. To our knowledge, this is the first human study to examine SV2A in vivo in MDD and PTSD and to use the first known drug (ketamine) that rapidly reverses synaptic loss to determine whether ketamine administration could restore some of the structural changes associated with depression and PTSD.
After a screening process to determine eligibility, all subjects will participate in an MRI, and 2-3 PET scans with the administration of ketamine for one of the scans. Cognitive testing and a stress test may also be done on scan days.
The goal of the study is to determine whether there are alterations in synaptic vesicle glycoprotein 2A (SV2A), a protein expressed ubiquitously in synaptic vesicles, in depression and anxiety and whether ketamine, an N-Methyl-D-aspartate (NMDA) antagonist, normalizes SV2A density at time of its greatest anti-depressant response. This study will conduct an examination of SV2A and associated consequences using neuroreceptor imaging and behavioral techniques for the following aims.
Aim 1: To compare SV2A availability in individuals with MDD, healthy control individuals, and individuals with PTSD using APP311 and PET.
Hypothesis 1: This study hypothesizes lower SV2A density in MDD and PTSD in the prefrontal cortex.
Aim 2: To determine whether ketamine administration alters SV2A density in HC, MDD, and PTSD individuals. Note: this arm is completed.
Hypothesis 2: This study hypothesizes administration of ketamine will lead to a significant increase in SV2A density in all subject groups (HC, MDD, and PTSD), and this increase will correlate with antidepressant response in individuals with MDD.
New Aim pending.
Condition | Major Depressive Disorder, Post-Traumatic Stress Disorder |
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Treatment | Ketamine, MRI, PET, Cognitive Testing |
Clinical Study Identifier | NCT02734602 |
Sponsor | Yale University |
Last Modified on | 30 April 2022 |
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