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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Depression; Anxiety
• Intervention / Treatment: Behavioral: Behavioral Activation; Behavioral: Exposure-based therapy; Behavioral: Supportive therapy

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mallory Cannon, M.S.; Phone Number: 918-581-4885; Email: neurocatt@laureateinstitute.org
• Study Contact Backup: Name: Robin L Aupperle, PhD; Phone Number: 918-502-5744; Email: raupperle@laureateinstitute.org

Study Locations

• United States
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Recruiting
      • Laureate Institute for Brain Research
      • Contact: Mallory Cannon, BA; Phone Number: 918-581-4885; Email: neurocatt@laureateinstitute.org
      • Contact: Robin Aupperle, PhD; Phone Number: 918-502-5744; Email: raupperle@laureateinstitute.org
      • Principal Investigator: Robin L Aupperle, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Supportive therapy	Behavioral: Supportive therapy; 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.
Experimental: Behavioral activation	Behavioral: Behavioral Activation; Behavioral activation will be delivered as a 10-week, manualized, behavioral intervention focused on enhancing engagement in meaningful and reinforcing activities.
Experimental: Exposure-based therapy	Behavioral: Exposure-based therapy; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amygdala reactivity to negative outcomes	Beta coefficient from general linear model for right amygdala region of interest in response to negative image outcome phase of an approach-avoidance conflict decision-making task. Standardized beta coefficients have a range of 0 to 1, with greater values indicating greater amygdala reactivity or worse outcomes.	Up to 14 weeks after the baseline assessments.
Dorsolateral prefrontal cortex reactivity to conflict decisions	Beta coefficient from general linear model for right dorsolateral prefrontal region of interest in response to the conflict decision phase of an approach-avoidance conflict decision-making task. Standardized beta coefficients have a range of 0 to 1, with greater values indicating greater dorsolateral prefrontal cortex reactivity.	Up to 14 weeks after the baseline assessments.
Dorsal striatal reactivity to negative outcomes	Beta coefficient from general linear model for dorsal striatal region of interest in response to negative image outcome phase of an approach-avoidance conflict decision-making task. Standardized beta coefficients have a range of 0 to 1, with greater values indicating greater striatal reactivity.	Up to 14 weeks after the baseline assessments.
Decision uncertainty during approach-avoidance conflict decision making	Decision uncertainty parameter from computational modeling of behavioral responses on the approach avoidance conflict task. Parameter values have a range of 0 to 20, with greater values indicating greater decision uncertainty.	Up to 14 weeks after the baseline assessments.
Emotional conflict during approach-avoidance conflict decision making	Emotional conflict parameter from computational modeling of behavioral responses on the approach avoidance conflict task. Parameter values have a range of 0 to 7, with greater values indicating greater conflict.	Up to 14 weeks after the baseline assessments.
Approach behavior during approach-avoidance conflict decision making	Average approach behavior on conflict trials of an approach avoidance conflict task. Average approach behavior values have a range of 0 to 10, with greater values indicating greater approach behavior.	Up to 14 weeks after the baseline assessments.
Bilateral amygdala volume	Gray matter volume of the bilateral amygdala	Up to 14 weeks after the baseline assessments.
Bilateral striatal volume	Gray matter volume of the bilateral striatum	Up to 14 weeks after the baseline assessments.
Bilateral hippocampal volume	Gray matter volume of the bilateral striatum	Up to 14 weeks after the baseline assessments.

Collaborators and Investigators

• Sponsor: Laureate Institute for Brain Research, Inc.
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Robin L Aupperle, PhD, Laureate Institute for Brain Research

Publications and helpful links

General Publications

• Aupperle RL, Melrose AJ, Francisco A, Paulus MP, Stein MB. Neural substrates of approach-avoidance conflict decision-making. Hum Brain Mapp. 2015 Feb;36(2):449-62. doi: 10.1002/hbm.22639. Epub 2014 Sep 15.
• Santiago J, Akeman E, Kirlic N, Clausen AN, Cosgrove KT, McDermott TJ, Mathis B, Paulus M, Craske MG, Abelson J, Martell C, Wolitzky-Taylor K, Bodurka J, Thompson WK, Aupperle RL. Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder. Trials. 2020 Jan 6;21(1):17. doi: 10.1186/s13063-019-3802-9.

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2020
• Primary Completion (Anticipated): June 30, 2025
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 10, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: 2020-003; R01MH123691 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication of results from the primary aims of this project, we intend to make the data used in publications (e.g., self-report, behavior, and neuroimaging data) accessible in a public database. These data will be stripped of patient identifiers and will comply with HIPAA requirements for publicly accessible datasets. User registration will be required to access or download files. As part of the registration process, users must agree to the conditions of use governing access to the public release data, including restrictions against attempting to identify study participants, destruction of the data after analyses are completed, reporting responsibilities, restrictions on redistribution of the data to third parties, and proper acknowledgement of the data resource.
• IPD Sharing Time Frame: Immediately after publication of results from the primary aims of this project.
• IPD Sharing Access Criteria: User registration will be required to access or download files. As part of the registration process, users must agree to the conditions of use governing access to the public release data, including restrictions against attempting to identify study participants, destruction of the data after analyses are completed, reporting responsibilities, restrictions on redistribution of the data to third parties, and proper acknowledgement of the data resource.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No