PET Imaging of mGLuR5 With Drug Challenge

This study is designed to look at that involvement of a process in the brain called the glutamate system in depression. Participants will undergo a screening session, up to two fMRI scans, and up to three PET scans, as well as cognitive testing at each scan session. For one of the PET scans, a drug (either ketamine or n-acetyl cysteine) will be administered.

Hypothesis 1: The investigators hypothesize administration of ketamine or n-acetylcysteine (NAC) will lead to a decrease in mGluR5.

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

Hypothesis 3: The investigators hypothesize an increase in mGluR5 availability and change in MRI measures post drug challenge as compared to baseline, signifying synaptogenesis.

Group 1: psychiatrically healthy subjects Group 2: depressed subjects with uni- or bipolar depression who have been antidepressant free

• MDD
  40 currently depressed subjects
• Healthy Control
  40 psychiatrically healthy subjects

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

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