Imaging SV2A in Mood Disorders

  • End date
    Mar 30, 2024
  • participants needed
  • sponsor
    Yale University
Updated on 30 April 2022
depressed mood
major depressive disorder
mood disorder
Accepts healthy volunteers


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
Treatment Ketamine, MRI, PET, Cognitive Testing
Clinical Study IdentifierNCT02734602
SponsorYale University
Last Modified on30 April 2022


Yes No Not Sure

Inclusion Criteria

General inclusion criteria
Subjects will be 18-70 years old
English speaking
No other DSM-5 diagnosis present, besides required as below
Inclusion criteria for depressed subjects
Meet DSM-5 diagnostic criteria for Major Depressive Disorder, and for a current depressive episode
Treatment or non-treatment seeking who understand that this study is for research purposes only
Inclusion criteria for healthy controls
No current, or history of any DSM-5 diagnosis
Inclusion criteria for PTSD subjects
Current Post Traumatic Stress Disorder

Exclusion Criteria

History of significant medical illness that would contraindicate study participation based on above criteria and PI/MD history review
Lifetime history of neurologic abnormality including seizure disorder, cerebrovascular or neoplastic lesion, neurodegenerative disorder, or significant head trauma resulting in post-traumatic amnesia >24 hours
Full scale IQ lower than 70
Contraindication to MRI scanning including claustrophobia and presence of a ferromagnetic object, including orthodontic braces. All participants will be screened for metal objects by the same methods used for routine clinical MRI scanning
Pregnancy or breast-feeding
Met DSM-5 criteria for mild substance use disorder (except nicotine and marijuana) within the past 6 months or met DSM-5 criteria for moderate to severe substance use disorder within the past year
Current psychosis, active suicidal or homicidal ideation
Positive urine toxicology screen (except for marijuana)
Contraindications to PET (e.g., past or current diagnosis of cancer, poor venous access for placement of venous lines)
History of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure
Previous or anticipated radiation exposure at work within one year of the proposed research PET scans that precludes study participation
Blood pressure >130/80 (for Aim 2, ketamine challenge); blood pressure >140/90 (non-ketamine groups)
History of a bleeding disorder or currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto)
Blood donation within eight weeks of the start of the study
Current diagnosis of MDD or PTSD with psychotic features
Hematocrit levels below 35 mg/dl, and/or hemoglobin levels below 10 mg/dl
Weight under 110 lbs for subjects who will participate in portions of this study for which the blood draw is at or above a typical blood donation
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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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