The Impact of Working Memory and Reward Markers on DLPFC Activity in Treatment-resistant Depression

Summary

Major Depressive Disorder (MDD) is a very common illness that is usually treated with antidepressant medication. Depression can be caused by many things such as childhood experiences, genetics, and changes in the way the body and brain function. For those with depression where medication and psychotherapy have limited benefit, repetitive transcranial magnetic stimulation (rTMS) is an effective treatment. rTMS is a treatment that involves stimulating certain areas of the brain with magnetic field pulses. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region. This can be helpful in treating some kinds of psychiatric and neurological disorder, including MDD.

It is not fully known how rTMS changes brain activity to improve symptoms of depression. However, certain brain areas responsible for behaviours impacted by depression are underactive in those with depression. One of those brain regions called the dorsolateral prefrontal cortex (DLPFC), and the investigators will target this region using rTMS. By increasing the activity of these regions, rTMS could potentially improve depression symptoms. For participants receiving rTMS, the investigators will be using the participant's brain scan to better understand brain activity of the brain region stimulated by rTMS before and after treatment.

In this study, the investigators will be collecting detailed information about participants' psychiatric history and depression symptoms, as well as brain scans and saliva samples. The saliva samples will undergo proteomic (having to do with proteins) analyses to identify biological markers ("biomarkers": biological features (e.g.: gene, protein) that can be measured to indicate factors related to rTMS response. The investigators' goal is to use this information to help us understand whether improvement to rTMS depends on brain activity or proteomic factors localized to two specific behaviours impacted by depression: reward processing and working memory (the capacity to hold information temporarily, such as holding a person's address in mind while listening to instructions about how to get there).

Conditions

• Major Depressive Disorder
• Treatment Resistant Depression

Interventions

DEVICE

Repetitive Transcranial Magnetic Stimulation

For those with depression where medication and psychotherapy have limited benefit, repetitive transcranial magnetic stimulation (rTMS) is an effective treatment. rTMS is a treatment that involves stimulating certain areas of the brain with magnetic field pulses. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region. This can be helpful in treating some kinds of psychiatric and neurological disorder, including MDD.

BEHAVIORAL

Research Interview, Questionnaires

Research Interview: A study team member will meet the participant to ask questions regarding the degree of depression at the beginning of the study. This interview will take approximately 30 minutes. Research Questionnaires: A study team member will ask the participant to complete questionnaires assessing the severity of the participant's depression, daily activities, personality/traits, and quality of life. Questionnaires will be completed via pen and paper at each visit. These questionnaires will take approximately 90 minutes to complete.

BEHAVIORAL

Brain Scan

The participant will be asked to undergo a magnetic resonance imaging (MRI) scan to look at the structure and function of their brain. The functional MRI measures the level of blood flow to areas of the brain associated with mood and behaviour, and the participant will be asked to complete two behavioural games while they are in the scanner. During the scan, the participant will be required to lie on a table within the cylindrical tube of the MRI scanner in order to complete the scan. This will result in limited movement for the duration of the scan. The scan will take approximately 60 minutes, and there will be a recovery period for 40 minutes. The participant will be given instructions about these tasks outside of the scanner. This brain scan will happen at St. Michael's Hospital.

BIOLOGICAL

Saliva Samples

The participant will be asked to provide six 1mL saliva samples during the MRI scan and recovery period so that the investigators can measure molecular markers associated with depression. In order to provide the sample, the investigators will collect their saliva using a cotton swab and test tube. Each sample should take no more than 5 minutes.

Sponsors & Collaborators

• Unity Health Toronto

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-01-31

Primary Completion

2026-12-31

Completion

2026-12-31

Countries

• Canada

Study Locations