PET Imaging of mGLuR5 With Drug Challenge

Participants undergo screening, up to two fMRI scans and up to three PET scans with cognitive testing at each session; one PET scan includes a drug challenge to provoke glutamate release.

Primary aims are to determine the acute effect of medication-induced glutamate release on mGluR5 availability and to assess cognitive effects and potential synaptogenesis measured by PET and MRI post-challenge.

Hypotheses include decreased mGluR5 after ketamine/NAC, improvements in memory and attention after challenge, and detectable increases in mGluR5 availability and MRI changes indicating synaptogenesis.

Inclusion Criteria:
18-65 years old
English speaking
No other Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (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 Hamilton Depression Rating Scale (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-Text Revision (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 Magnetic Resonance (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

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Acute cognitive effects of single-dose intravenous ketamine in major depressive and posttraumatic stress disorder

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