Approach-Avoidance, Computational Framework for Predicting Behavioral Therapy Outcome (AAC-BeT)

Study Overview
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Brief Summary
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Depression and anxiety disorders rank in the top ten causes of years lived with disability. Less than 50% of patients experiencing long-lasting improvements to current gold-standard treatments. Two gold-standard behavioral interventions include behavioral activation, focused on enhancing approach behavior towards meaningful activities, and exposure-based therapy, focused on decreasing avoidance and challenging negative expectations. While these interventions have divergent treatment targets, there is little knowledge to inform which strategies should be used in the frequent case of comorbid anxiety and depression. Approach-avoidance decision-making paradigms focus on assessing responses when faced with potential rewards and threats, tapping into processes important for both anxiety and depression as well as behavioral activation and exposure-based therapy. For this study, investigators will recruit individuals reporting both anxiety and depression symptoms and randomize them to one of three different interventions: (1) behavioral activation, (2) exposure-based therapy, and a non-specific therapy approach (3) supportive therapy. Participants will complete clinical, self-report, behavioral, and functional magnetic resonance imaging (fMRI) assessments before and after therapy. Investigators will use a computational approach to model factors that may influence one's behavior during approach-avoidance decision-making, including drives to avoid threat versus approach reward and confidence versus uncertainty in one's decisions. This project will accomplish the following aims (1) Determine how changes in brain and behavior responses during approach-avoidance conflict relate to changes in mental health symptoms with the different therapy approaches, (2) Determine the degree to which baseline brain and behavior responses during approach-avoidance conflict predict response to the different therapy approaches, above and beyond the influence of demographics and baseline symptom severity. In addition, by including peripheral blood draws and measures of grace matter volume, the project will also accomplish the following aims: (1) Determine whether kynrenine metabolites measures peripherally may be beneficial as a biomarker of treatment response and (2) determine whether there is an association between change in kynurenine metabolites and changes in gray matter volume with treatment. Results will enhance understanding of how different psychotherapy approaches (behavioral activation, exposure-based therapy) may impact brain responses and decisions when faces with potential reward versus threat and approach versus avoidance drives. In addition, results will have important implications concerning the potential for a more personalized approach to psychotherapy, enhancing knowledge of which types of therapy strategies may be most beneficial for which individuals.

Official Title
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An Approach-Avoidance, Computational Framework for Predicting Behavioral Therapy Outcome in Anxiety and Depression (AAC-BeT)

Conditions
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Anxiety, Depression

Intervention / Treatment
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* Behavioral: Behavioral Activation
* Behavioral: Exposure-based therapy
* Behavioral: Supportive therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: score >55 on both the PROMIS Anxiety and PROMIS Depression scales score >5 on any one item of the SDS able to provide informed consent report of anxiety and depressive symptoms as areas of clinical concern sufficient English proficiency to complete procedures. Exclusion Criteria: significant or unstable physical or mental health conditions (e.g., immediate suicidal intent) requiring medical attention history of bipolar, psychotic, cognitive, obsessive compulsive disorder, posttraumatic stress disorder (PTSD) history of moderate to severe substance use disorder over the past year diagnosis of neurologic disorders MRI contra-indications (e.g., metal in body) uncorrected vision/hearing problems current, regular benzodiazepine use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to behavioral activation, exposure-based, or supportive therapy according to parallel assignment, stratified by sex (male, female) and symptom severity (mild, moderate, severe).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Behavioral activation<br> | Behavioral: Behavioral Activation<br>* Behavioral activation will be delivered as a 10-week, manualized, behavioral intervention focused on enhancing engagement in meaningful and reinforcing activities.<br>|
| Experimental: Exposure-based therapy<br> | Behavioral: Exposure-based therapy<br>* Exposure-based therapy will be delivered as a 10-week, manualized, behavioral intervention focused on decreasing avoidance to allow for inhibitory learning and challenging negative expectations.<br>|
| Active Comparator: Supportive therapy<br> | Behavioral: Supportive therapy<br>* Supportive therapy will be delivered as a 10-week, manualized intervention focused on encouraging patients to talk openly about their thoughts, emotions, and any past or current concerns.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite score from Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D) | Composite score (averaging of the standardized Z scores) from the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D). These Z scores will range from -3.0 to +3.0, with greater scores indicating more severe anxiety and depression symptoms or worse outcome. | Up to 18 weeks after the baseline assessments | 
| Quinolinic Acid | Peripheral serum concentration of Quinolinic Acid | Up to 18 weeks after the baseline assessments | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sheehan Disability Scale | Sheehan Disability Scale total score. This score ranges from 0-30, with higher scores indicating greater disability or worse outcome. | Up to 18 weeks after the baseline assessments | 
| National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Anxiety Scale | National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Anxiety Scale, which is reported as a T score. The T scores can range from - to 100, with a mean of 50 and a standard deviation of 10. Higher scores indicate greater symptom severity or worse outcome. | Up to 18 weeks after the baseline assessments | 
| National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Depression Scale | National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Depression Scale, which is reported as a T score. The T scores can range from - to 100, with a mean of 50 and a standard deviation of 10. Higher scores indicate greater symptom severity or worse outcome. | Up to 18 weeks after the baseline assessments | 
| Kynurenic acid | Peripheral serum concentration of kynurenic acid | Up to 14 weeks after the baseline assessments | 
| Ratio of kynurenic acid to quinolinic acid | Ratio of peripheral serum concentration of kynurenic acid to quinolinic acid | Up to 14 weeks after the baseline assessments | 
| Ratio of kynurenic acid to tryptophan | Ratio of peripheral serum concentration of kynurenic acid to tryptophan | Up to 18 weeks after the baseline assessments |