Imaging Synapses With [11C] UCB-J in the Human Brain

Imaging Synapses With [11C] UCB-J in the Human Brain

The purpose of this study is to utilize the radioactive positron emission tomography (PET) tracer [11C]UCB-J to test the neural synaptic pruning hypothesis of schizophrenia. This imaging method allows for the quantification of synaptic density in the living human brain and has the unprecedented ability to directly examine the synaptic pathology underlying neuropsychiatric disease. The neural synaptic pruning hypothesis posits that a key pathogenic process of schizophrenia is the over-exuberant elimination of neural synapses during development. The confirmation of reduced synaptic density in schizophrenia as evidenced by [11C]UCB-J has the potential to lead to a number of ground-breaking clinical innovations, such as laboratory-based diagnostics and prognostics, and novel, disease-modifying treatments.

Inclusion Criteria:

• 18 - 65 years in age

• For SZ participants:

  • On a stable medication regimen for at least two weeks prior to testing
  • A clinical diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder
  • Able to complete a PET-MR scan without the use of sedation

Exclusion Criteria:

• Active substance use within three months of testing

• IQ < 70

• Major medical neurological illness or significant head trauma

• Pregnancy or breastfeeding

• Contraindication to MR scanning, including magnetic-resonance incompatible metal or hardware including pacemakers, cochlear implants, and bullets near a critical organ

• Weight > 350 lbs or a large body habitus that MR scanner cannot accommodate

• History of or current claustrophobia

• Inability to comply with basic study requirements such as following directions and punctuality

• For HC participants:

  • Presence of a first degree relative with a psychotic disorder
  • Lifetime diagnosis of major psychiatric illness

• For SZ participants:

  • Unstable psychiatric symptoms at the time of testing, e.g. acute suicidality, prominent psychosis, or behavioral dyscontrol