Social Reward and Its Effect on Brain Functions in Psychotherapies for Mid- and Late-Life Depression

Study Overview
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Brief Summary
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Abnormalities in the Positive Valence System (PVS) are associated with depressive symptoms and reduced behavioral activation in mid- and late-life. This study will investigate the engagement of the PVS during exposure to social rewards, part of a novel streamlined psychotherapy for mid- and late-life depression. Use of computational modeling will enable identification of neuroimaging and behavioral profiles associated with greater treatment response, and may guide future personalization of psychotherapy.

Official Title
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Social Reward and Its Effect on Brain Functions in Psychotherapies for Mid- and Late-Life Depression

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Behavioral: Engage & Connect Psychotherapy
* Behavioral: Symptom Review and Psychoeducation (SRP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages aged 50-85 [stratified so that 50% are older than 65] Diagnosis of unipolar major depressive disorder without psychotic features, determined by the SCID Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 20. Mini Mental Status Exam (MMSE) ≤ 1 SD below the mean score for patient's age and education Off antidepressants or on a stable dose of an antidepressant for 8 weeks and do not intend to change the dose in the next 10 weeks. Capacity to provide written consent for research assessment and treatment. Exclusion Criteria: Intent or plan to attempt suicide in the near future. History or presence of psychiatric diagnoses other than major depressive disorder without psychotic features, generalized anxiety disorder, or specific phobia. Use of psychotropic drugs or cholinesterase inhibitors other than use of ≤ 0.5 mg of lorazepam daily up to seven times per week. Neurological disorders (dementias, history of stroke, multiple sclerosis, Parkinson's disease, epilepsy, etc.); cardiac, renal, or respiratory failure; severe chronic obstructive pulmonary disease; metastatic cancer; or debilitated states or less common medical illnesses that may either influence brain systems of interest or ability to participate in the study. Dr. Alexopoulos or another research psychiatrist will review any medical illnesses that does not appear in the list above and determine whether it interferes with the study of positive valence system functions in depression. Contraindications to MRI scanning including cardiac pacemaker, heart valve replacement, vascular stent, insulin pump, cochlear implant, any other metallic biomedical implant contraindicating to MRI, and claustrophobia.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized controlled trial. Participants will be randomly assigned to 9-weeks of either Engage-S Psychotherapy or Symptom Review and Psychoeducation (SRP) Psychotherapy
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Engage & Connect Psychotherapy<br>Engage & Connect, a modified adapted version of Engage. Its principal intervention is social reward exposure - facilitating engagement in rewarding and meaningful social activities with significant others. In Engage-S therapy, individuals with depression work with a therapist to develop action plans to pursue rewarding social activities of their choice. | Behavioral: Engage & Connect Psychotherapy<br>* 9-weeks of weekly psychotherapy sessions focused on social reward exposure<br>|
| Active Comparator: Symptom Review and Psychoeducation (SRP)<br>In this intervention, the therapist will review the participant's symptoms and provide literature-based clinical explanations and clarifications about the symptoms, the course, and the causes of depression. In SRP, the therapist reviews the depressed individual's symptoms, and level of information on depression, identifies misconceptions, and guides selection of educational material which could benefit the patient. | Behavioral: Symptom Review and Psychoeducation (SRP)<br>* 9-weeks of weekly psychotherapy sessions focused on symptom review and psychoeducation about depression and aging<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Resting State fMRI Connectivity of the Positive Valence System | Calculated from fMRI scan. Validation of target engagement. | Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery Asberg Depression Rating Scale (MADRS) | 10-item Clinician rated measure of depression severity. Scores range from 0 (no depression) to 60 (severe depression). | Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9) | 
| Change in Behavioral Activation for Depression Scale (BADS) | 25-item measure self-report measure of behavioral activation. Scores range from 0 (very low behavioral activation) to 150 (high behavioral activation). | Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Late Life Depression, Psychotherapy, Mechanisms of Action, Positive Valence System, Social Reward