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, 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.

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.

Inclusion Criteria:

- General inclusion criteria:

1. Subjects will be 18-55 years old,

2. English speaking,

3. No other DSM-IV diagnosis present, besides required as below.

Inclusion criteria for depressed subjects:

1. Meet DSM-IV diagnostic criteria for Major Depressive Disorder, and for a current
depressive episode.

2. Treatment or non-treatment seeking who understand that this study is for research
purposes only.

Inclusion criteria for healthy controls:

1. No current, or history of any DSM-IV diagnosis,

2. No first-degree relative with history of psychotic, mood, or anxiety disorder.

Inclusion criteria for PTSD subjects:

1. Current Post Traumatic Stress Disorder.

Exclusion Criteria:

1. History of significant medical illness.

2. Lifetime history of neurologic abnormality including significant head trauma, seizure
disorder, cerebrovascular or neoplastic lesion, or neurodegenerative disorder.

3. Full scale IQ lower than 70.

4. 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.

5. Pregnancy or breast-feeding.

6. Alcohol/illicit substance dependence in the past year or met alcohol/illicit substance
abuse within the past 6 months.

7. Current psychosis, active suicidal or homicidal ideation.

8. Positive urine toxicology screen.

9. Contraindications to PET (e.g., past or current diagnosis of cancer, poor venous
access for placement of venous lines).

10. 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.

11. Previous or anticipated radiation exposure at work within one year of the proposed
research PET scans that precludes study participation.

12. Blood pressure >140/80.

13. History of a bleeding disorder or currently taking anticoagulants (such as Coumadin,
Heparin, Pradaxa, Xarelto).

14. Blood donation within eight weeks of the start of the study.

15. Current diagnosis of MDD or PTSD with psychotic features.

16. First degree relative with a diagnosis of a psychotic disorder. -