Recurrence Markers, Cognitive Burden and Neurobiological Homeostasis in Late-Life Depression (REMBRANDT)

Late-life depression (LLD) is associated with disability, increased risk for cognitive decline and dementia, elevated suicide risk, and greater all-cause mortality. These outcomes are related to depression being a recurrent disorder, with repeated episodes over a patient's lifetime. Recurrence rates (defined as including both relapse and recurrence) are high in LLD.

The goals of this study are to identify neurobiological factors that predict recurrence risk, and examine how cognitive performance changes are both influenced by these neurobiological factors and also predict recurrence risk.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrence; Cognitive Dysfunction; Depression in Old Age

• Study Type: Observational
• Enrollment (Estimated): 210

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60607
      • University of Illinois at Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

We will enroll patients from clinical referrals and response to advertisements. For clinical referrals, referring providers may either provide information about the study to the participant, including our contact information. Alternatively, they may obtain permission from the participant for the study team to contact them. With the clinician's agreement, study staff can review their clinic schedules to help identify potentially eligible patients, however data will not be recorded for research purposes. Advertisements may include radio, newspapers, internet, online research registries, public transportation, and flyers / brochures.

Description

Inclusion Criteria:

• Currently depressed participants (who will enter the treatment algorithm): 1) Age > 60 years; 2) diagnosis of major depressive disorder, recurrent episode (DSM5); 3) severity: Montgomery Asberg Depression Rating Scale (MADRS) (67) ≥ 15; 4) cognition: Montreal Cognitive Assessment (MoCA) >24 or Montreal Cognitive Assessment (MoCA) - BLIND ≥ 18; 5) fluent in English.
• Remitted depressed participants (who will directly enter the longitudinal study): 1) Age > 60 years; 2) diagnosis of major depressive disorder, recurrent, in partial or full remission (DSM5); 3) severity: MADRS < 10; 4) cognition: MoCA >24 or Montreal Cognitive Assessment (MoCA) - BLIND ≥ 18; 5) fluent in English.
• Never- depressed elders: 1) Age > 60 years; 2) severity: MADRS < 8; 3) cognition: MoCA >24 or MoCA - BLIND ≥ 18; 4) fluent in English.

Exclusion Criteria:

• Currently depressed participants (who will enter the treatment algorithm): 1) Other Axis I psychiatric disorders, except for simple phobia or anxiety disorders present during the depressive episode (e.g., generalized anxiety disorder (GAD) or panic disorder symptoms); 2) History of alcohol or drug dependence or abuse (other than nicotine) in the last year; 3) History of a developmental disorder or history of IQ < 70; 4) Acute suicidality within 3 months of study entry; 5) Acute grief (<1 month); 6) Current or past psychosis; 7) Primary neurological disorder, including dementia, clinical stroke, brain tumor, epilepsy, etc.; 8) Presence of unstable medical illness requiring urgent treatment; 9) Any MRI contraindication; 10) ECT in last 6 months; 11) Vagal Nerve Stimulation within 6 months of study entry; 12) Current use of TMS, ketamine, or esketamine with plans to continue treatment.
• Remitted depressed participants (who will directly enter the longitudinal study): Identical to the currently depressed participants, plus 1) currently receiving brain stimulation treatment (ECT, TMS, VNS), ketamine or esketamine. There are no other exclusions for antidepressant treatment.
• Never- depressed elders: Identical to the currently depressed participants, plus: 1) No diagnosis of current or past depressive disorder or other Axis I disorder except for simple phobia; 2) No history of psychotropic medication use for psychiatric symptoms.

We will not be enrolling vulnerable populations, specifically pregnant women, children, prisoners, or institutionalized individuals. We also will not enroll subjects incapable of providing their own consent. Should a potential subject present where there is a concern (either by a study clinician or staff member) about their ability to understand study procedures and provide meaningful consent, their cognitive ability and understanding will be evaluated by a study doctor. If there is any concern that the individual may be impaired, they will not be enrolled in the study. The rationale will be provided to the individual as well as his or her family members. Referrals for further evaluation, including urgent or emergent evaluation, will be made as needed and clinically warranted.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Currently Depressed Participants; Individuals who are currently depressed and receive treatment through an antidepressant treatment
Remitted Depressed Participants; Individuals who have achieved remission from depression within 4 months
Remitted Depressed Elders; Individuals who no lifetime history of depression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurobiology of Recurrence (Stress Reactivity)	Stress reactivity measured experimentally (neural reactivity during fMRI stress induction task) and ecologically (affective instability by ecological momentary assessment).	Change in stress reactivity at Month 8, Month 16, and Month 24
Neurobiology of Recurrence (Functional Network Connectivity)	Alterations in functional network connectivity which includes both intra/internetwork connectivity markers and well as markers of network instability.	Change in functional network connectivity at Month 8, Month 16, and Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cognitive Function	Cognition will be assessed a conventional, broad-based battery.	Change in cognitive function at Month 0 and Month 24

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: National Institute of Mental Health (NIMH); University of Pittsburgh; Vanderbilt University Medical Center
• Investigators: Study Chair: Amruta Barve, MPH, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): May 15, 2025
• Study Completion (Estimated): January 15, 2026

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Depression; Recurrence; Cognitive Dysfunction; Antidepressive Agents; Depression in Old Age; Neurobiological Markers; Anxiety Depression
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease Attributes; Behavioral Symptoms; Neurocognitive Disorders; Cognition Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Cognitive Dysfunction; Recurrence; Depression
• Other Study ID Numbers: 2020-0078; 1R01MH121384-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No