PET Imaging of mGLuR5 With Drug Challenge

Aim 1: To determine the acute effect of medication-induced glutamate release on mGluR5
availability in human subjects. Hypothesis 1: We hypothesize administration of ketamine or
n-acetylcysteine (NAC) will lead to a decrease in mGluR5 availability.

Aim 2: To determine if glutamate release via administration of ketamine or NAC has pro
cognitive benefits.

Hypothesis 2: We hypothesize an improvement in memory and attentional skills after drug
challenge.

Aim 3: To determine if there is synaptogenesis detectable by PET and MRI post ketamine or
NAC within a week of drug challenge (at the time of greatest antidepressant response).
Hypothesis 3: We hypothesize an increase in mGluR5 availability and change in MRI measures,
post drug challenge as compared to baseline, signifying synaptogenesis.

Aim 4: To determine if there is a difference in reduction of mGluR5 availability after
ketamine administration when radiotracer is administered bolus as compared to bolus to
constant infusion in the same subjects (ABP688 radiotracer only).

Hypothesis 4: We expect there should not be a significant difference in reduction in mGluR5
availability due to differences in ABP688 radiotracer infusion.

Inclusion Criteria:

- 18-65 years old

- English speaking

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

Inclusion criteria for depressed subjects

- clinical diagnosis of a current or past depressive episode

- medication free for at least 2 weeks

- Score >16 on HDRS if currently depressed or <11 if not currently depressed

- 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-IV diagnosis

- no first-degree relative with history of psychotic, mood, or anxiety disorder

Inclusion criteria for PTSD subjects

- current Post-Traumatic Stress Disorder, as determined by the Structured Clinical
Interview for DSM-IV-TR (SCID) patient research edition

- Clinician Administered PTSD Scale for DSM-IV-TR (CAPS) score of 50 or higher

Inclusion criteria for trauma control subjects

-history of trauma (meeting the criterion A of PTSD but not a full diagnosis of PTSD)

Exclusion Criteria:

- Current or past significant medical, neurological, or metabolic disorder or loss of
consciousness for 5 minutes or more

- active, significant suicidal ideation

- implanted metallic devices or any MR contraindications

- women who are pregnant or breastfeeding

- met DSM-IV criteria for alcohol/illicit substance dependence in their life-time or
met alcohol/illicit substance abuse within past year

- 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. This guideline is an effective dose of 5 rem received per year

- blood donation within eight weeks of the start of the study

- radiation exposure at work that precludes study participation

- blood pressure >140/80