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NCT Number: NCT07091643

Neuroimaging Markers of Midlife Depression and Cognitive Behavioural Therapy (CBT)

Major depressive disorder (MDD) is associated with significant cognitive impairment throughout the life-course, which may progress toward MCI and dementia with age. Antidepressant medications are the first line of treatment; however, they fail to adequately address cognitive deficits and prevent relapse. Sustained cognitive impairment into euthymic periods may relate to underlying neurobiological changes, which could potentially be addressed through Cognitive Behavioural Therapy (CBT). Notably, CBT has been shown to improve cognitive domains including divided attention, memory, and processing speed while preventing depression relapse. Midlife represents a critical period in which shared neurobiological factors (such as brain changes on a vascular, morphological, and functional level) underlying depression and cognitive impairment could accelerate toward MCI and dementia. An updated understanding of neurobiological correlates of midlife depression and CBT response through multimodal neuroimaging is critical to improving affective and cognitive outcomes in this population.

The overarching objective of this project is to use multimodal neuroimaging to quantify the neurobiological and clinical impact of CBT in midlife depression. Specifically, we aim to:

1. Investigate the clinical impact of CBT on cognitive function and mood outcomes in midlife depression 2. Examine functional connectivity and microstructural determinants of CBT response in midlife depression using neuroimaging 3. Identify vascular modulators of neural connectivity and CBT response in midlife depression.

We hypothesize that midlife depression will be associated with functional and structural neural connectivity changes, which will be accompanied by vascular pathology. Adequate CBT response (i.e., improvements in mood and cognitive function) will be associated with amelioration of neurobiological changes.

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Key information

Conditions

Major Depressive Disorder (MDD) Behavior Behavioral Symptoms Depression Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

40 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 40-60 years, inclusive.
  • Diagnosis of MDD as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)6 determined through a structured clinical interview.
  • Current major depressive episode of at least 3 months in length.
  • Depression of at least mild severity defined by a total score of ≥7 on the Montgomery Asberg Depression Rating Scale (MADRS)7.
  • Ability to understand and comply with the requirements of the study, as judged by the investigator(s).

Exclusion criteria

  • Presence of comorbid post-traumatic stress disorder, obsessive-compulsive disorder, eating disorder(s), schizophrenia, or other psychiatric disorders.
  • History of a manic, hypomanic, or mixed depressive episode.
  • Treatment with electroconvulsive therapy, intravenous and/or intranasal ketamine in the 6-weeks prior to study enrolment.
  • History of substance-use disorder in the past 12 months.
  • Presence of current alcohol-use disorder
  • A positive urine toxicology screen for non-prescribed substance use.
  • A positive pregnancy test at screening.
  • A history of major medical or neurological illness.
  • A history of traumatic brain injury, stroke, seizures, or previous brain surgery.
  • Contraindications to magnetic resonance imaging (MRI) scanning.

Treatment and study plan

Cognitive Behavioural Therapy

Behavioral

12 weeks of Cognitive Behavioural Therapy (CBT) will be administered. The first session will be accomplished in-person at Baycrest Hospital. After that, therapy will be conducted virtually, via video-conference. Individuals will undergo therapy once a week for approximately 1 hour, for 12-weeks. Following the 12-week period, individuals will receive three follow-up assessments with their therapist at 3, 6, and 9 months.

Primary outcomes

  1. MADRS

    Time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).

    The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated scale used to assess the severity of depressive symptoms. It is a 10-item scale, with each item rated on a 7-point scale, and the total score ranges from 0 to 60, with higher scores indicating more severe depression. The MADRS is commonly used in clinical trials and research to evaluate treatment response in individuals with depression.

  2. DARS

    Time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).

    The Dimensional Anhedonia Rating Scale (DARS) is a 17-item self-report scale used to assess anhedonia, a core symptom of depression characterized by a reduced ability to experience pleasure. It measures anhedonia across four domains: hobbies, food/drink, social activities, and sensory experiences, evaluating aspects like desire, motivation, effort, and consummatory pleasure.

Secondary outcomes

  1. T1-anatomical

    Time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).

    A T1 anatomical MRI, also known as a T1-weighted MRI, is a type of magnetic resonance imaging (MRI) sequence that excels at visualizing the structural details of tissues, particularly soft tissues and fat. It's often used to provide a clear view of the b

  2. Diffusion-tensor MRI

    Time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).

    Diffusion tensor MRI (DTI) is an advanced magnetic resonance imaging (MRI) technique that maps the diffusion of water molecules in the brain to visualize the white matter pathways. It provides insights into the structural organization and integrity of white matter, which is crucial for understanding brain connectivity and function.

  3. Resting-state fMRI

    Time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).

    Resting state fMRI (rs-fMRI) is a technique used to study brain activity when a person is not performing a specific task. It focuses on spontaneous fluctuations in the blood-oxygen-level-dependent (BOLD) signal to identify functional connections between different brain regions. We will use this signal to compute functional connectivity

Study contacts

Contact information is provided by the study sponsor or research team.

Principal Investigator

CONTACT

[email protected]

416-785-2500 ext. 2017

Sponsors and collaborators

Lead sponsor

Baycrest

Other

Registry information

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Jul 29, 2025
Registry last updated
Feb 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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