Treatment Resistant DepressionDepression - Major Depressive Disorder
Investigational drug(s) / intervention(s)
PET scans
PET scans: PET scans and PHNO scans
Study summary
The purpose of this study is to better understand how certain brain systems work in people with depression, especially in those whose symptoms have not improved with antidepressant treatments. The investigators are particularly interested in synaptic density, which helps to understand how different parts of the brain communicate with one another. Synaptic density levels have implications on overall brain function and cognition. By comparing brain function in people with treatment-resistant depression, people with treatment-responsive depression, and healthy controls, investigators hope to better understand why some individuals do not respond to antidepressants. This research may help guide the development of more effective treatments in the future.
Eligibility
Sex
ALL
Min age
25 Years
Max age
65 Years
Healthy volunteers
Accepted
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
Primary outcome measure(s)
Synaptic Density — 3 years Synaptic density represents a promising biomarker for TRD, as it provides a direct index of neural circuit integrity and synaptic architecture (Appelbaum et al, 2022; Serano et al, 2022). Interventions shown to be effective in treatment-resistant populations, including rapid-acting antidepressants and neuromodulatory approaches, have been proposed to engage in synaptic plasticity-related mechanisms (Duman et al, 2016). As such, synaptic density measured using SV2A PET may offer insight into circuit-level abnormalities relevant to depression severity and treatment resistance, therefore offering a mechanistically informed approach for characterizing the biological correlates of TRD and supports its use in PET-based investigations of this population
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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