Characterizing Synaptic Density in Treatment Resistant Depression

This research project examines synaptic density in the brain. Synaptic density refers to the number of communication connections that exist between brain cells in a given area, which provides researchers with information about how efficiently brain regions communicate. Researchers are studying synaptic density to better understand how brain communication may differ in people with depression.

It is estimated that 30% of individuals with Major depressive Disorder (MDD) fail to respond to conventional antidepressant medication. Treatment resistant depression (TRD) patients also are more likely to have other psychiatric and medical diagnoses, poorer quality of life, and increased suicidal ideation. There are few treatment strategies available to target TRD and there is not a lot of evidence about how TRD differs from depression that responds to treatment.

In this study, we will be collecting detailed information about your psychiatric history and depression symptoms, as well as two brain scans using positron emission tomography (PET) and magnetic resonance imaging (MRI). PET imaging uses a radioactive agent (also called a tracer) to obtain pictures of the brain. The tracer we will use is called [18F]- SynVesT-1, which measures synaptic density. In addition, the MRI scan will be used to examine your brain function when performing tasks involved in memory and learning about rewards. The ultimate goal of this study is to better understand synaptic density in your brain and how it relates to brain function during memory and reward learning tasks. This information will be important for advancing our knowledge of the brain biology of TRD and potential new areas for treatment development.

Inclusion criteria

• Key inclusion criteria for the MDD patients:

• DSM-5 criteria for a Major Depressive Episode (MDE) within a MDD, confirmed through MINI diagnosis (Sheehan et al, 2015)
• Age between 25 and 65 years
• Hamilton Depression Rating Scale - 17 item (HRSD-17; Hamilton, 1960) > 14 (moderate to severe symptoms)
• Free of psychotropic medications (with the exception of SSRIs or SNRIs) for at least 5 half-lives before PET scanning per investigator discretion, after which an insignificant amount of drug is circulating through the body and accessing the brain. This determination will be based on self-report from the participant of when their last dose was. Use of benzodiazepines (except for diazepam) or sedative hypnotics (e.g. zopiclone) is allowable, but the last dose must be at least 72 hours prior to scanning.
• Ability to undergo MRI scanning (absence of metal, pacemakers, etc.)
• For non-resistant patients: Previous history of response to an antidepressant, in order to increase signal to noise between resistant and non-resistant patients

Key inclusion criteria for the Healthy Controls:

• Ages between 25 and 65 years
• Ability to undergo MRI scanning (absence of metal, pacemakers, etc.)

Exclusion criteria

Key exclusion criteria for the MDD patients:

• Pregnancy/lactation
• Medical condition requiring immediate investigation or treatment
• Recent (< 6 months)/current history of drug abuse/dependence
• Lifetime history of psychosis, other Axis I comorbidities are allowable
• Use of any psychotropic use within 5 half-lives before the PET scanning, with the exception of SSRIs and SNRIs
• For non-resistant patients: Failure of > 2 antidepressant treatments of adequate dose and duration for current MDE.

Key exclusion criteria for the Healthy Controls:

• Pregnancy/lactation
• Medical condition requiring immediate investigation or treatment
• Lifetime history of any psychiatric disorder
• Lifetime history of receiving an antidepressant