Imaging SV2A in Mood Disorders

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, bipolar individuals, and individuals with PTSD using APP311 or SDM-8 (aka SynVesT-1) and PET.

Hypothesis 1: This study hypothesizes lower SV2A density in MDD, BD, and PTSD in the prefrontal cortex.

Aim 2: To determine whether ketamine administration alters SV2A density in HC, MDD, and PTSD individuals.

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.

Aim 3: To determine the extent of SV2A density changes after prolonged treatment with ketamine in individuals with depression (n=10).

Hypothesis 3: We hypothesize ketamine treatment will increase SV2A density in these individuals. These are individuals who are undergoing ketamine treatment at Yale, CMHC, or surrounding clinics.

Aim 4: To examine changes in SV2A associated with gender within each psychiatric group.

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.

Inclusion criteria

for bipolar subjects:

• Meet DSM-5 diagnostic criteria for bipolar disorder.

Inclusion criteria

for subjects undergoing ketamine treatment

• Meet DSM-5 diagnostic criteria for Major Depressive Disorder, and for a current depressive episode, as assessed by structured interview for DSM-5 diagnosis (SCID).
• Undergoing ketamine treatment.

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.
• Claustrophobia.
• 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).
• Arterial line exclusion: History of a bleeding disorder or currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto).
• Arterial line exclusion: 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.