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

NCT07091643 | Not Yet Recruiting

• 1 other identifier: REB 22-10
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Major Depressive Disorder (MDD)

Keywords

Midlife Depression; Depression; Cognitive Behavioural Therapy (CBT)

Outcome Measures

Primary Outcomes (2)

• MADRS

  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.

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

• DARS

  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.

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

Secondary Outcomes (3)

• T1-anatomical

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

• Diffusion-tensor MRI

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

• Resting-state fMRI

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

Study Arms (1)

Experimental Group

EXPERIMENTAL

Individuals with midlife depression (MDD, ages 40-60 years) will undergo 12 weeks of CBT, in addition to three follow-up assessments, clinical evaluation (including completion of self-report and clinician-rated questionnaires) and pre-post CBT magnetic resonance imaging (MRI).

Behavioral: Cognitive Behavioural Therapy

Interventions

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.

Experimental Group

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baycrest: lead

Study Sites (1)

Baycrest Hospital

Toronto, Ontario, M6A 2E1, Canada

Location

Related Publications (5)

• World Health Organization. Division of Mental Health and Prevention of Substance Abuse. (1997). WHOQOL : measuring quality of life. World Health Organization.

  BACKGROUND

• Leach, L., Kaplan, E., Rewilak, D., Richards, B., & Proulx, G. (2000). The Kaplan-Baycrest neurocognitive assessment (KBNA): Test manual. San Antonio, TX, Harcourt Assessment.

  BACKGROUND

• Soares CN. Mood disorders in midlife women: understanding the critical window and its clinical implications. Menopause. 2014 Feb;21(2):198-206. doi: 10.1097/GME.0000000000000193.

  PMID: 24448106 BACKGROUND

• Perini G, Cotta Ramusino M, Sinforiani E, Bernini S, Petrachi R, Costa A. Cognitive impairment in depression: recent advances and novel treatments. Neuropsychiatr Dis Treat. 2019 May 10;15:1249-1258. doi: 10.2147/NDT.S199746. eCollection 2019.

  PMID: 31190831 BACKGROUND

• Brenowitz WD, Zeki Al Hazzouri A, Vittinghoff E, Golden SH, Fitzpatrick AL, Yaffe K. Depressive Symptoms Imputed Across the Life Course Are Associated with Cognitive Impairment and Cognitive Decline. J Alzheimers Dis. 2021;83(3):1379-1389. doi: 10.3233/JAD-210588.

  PMID: 34420969 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Central Study Contacts

Principal Investigator

CONTACT

416-785-2500; jean.chen@utoronto.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist

Study Record Dates

• First Submitted: July 22, 2025
• First Posted: July 29, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 27, 2026

Record last verified: 2025-07

Locations

CA (1)