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NCT Number: NCT04426461

Approach-Avoidance, Computational Framework for Predicting Behavioral Therapy Outcome (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.

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Key information

Conditions

Anxiety Anxiety Disorders Behavior Behavioral Symptoms Depression Mental Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Behavioral Activation

Behavioral

Behavioral activation will be delivered as a 10-week, manualized, behavioral intervention focused on enhancing engagement in meaningful and reinforcing activities.

Exposure-based therapy

Behavioral

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.

Supportive Therapy

Behavioral

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.

Primary outcomes

  1. Composite score from Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D)

    Time frame: Up to 18 weeks after the baseline assessments

    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.

  2. Quinolinic Acid

    Time frame: Up to 18 weeks after the baseline assessments

    Peripheral serum concentration of Quinolinic Acid

Secondary outcomes

  1. Sheehan Disability Scale

    Time frame: Up to 18 weeks after the baseline assessments

    Sheehan Disability Scale total score. This score ranges from 0-30, with higher scores indicating greater disability or worse outcome.

  2. National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Anxiety Scale

    Time frame: Up to 18 weeks after the baseline assessments

    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.

  3. National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Depression Scale

    Time frame: Up to 18 weeks after the baseline assessments

    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.

  4. Kynurenic acid

    Time frame: Up to 14 weeks after the baseline assessments

    Peripheral serum concentration of kynurenic acid

  5. Ratio of kynurenic acid to quinolinic acid

    Time frame: Up to 14 weeks after the baseline assessments

    Ratio of peripheral serum concentration of kynurenic acid to quinolinic acid

  6. Ratio of kynurenic acid to tryptophan

    Time frame: Up to 18 weeks after the baseline assessments

    Ratio of peripheral serum concentration of kynurenic acid to tryptophan

Other outcomes

  1. Amygdala reactivity to negative outcomes

    Time frame: Up to 14 weeks after the baseline assessments.

    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.

  2. Dorsolateral prefrontal cortex reactivity to conflict decisions

    Time frame: Up to 14 weeks after the baseline assessments.

    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.

  3. Dorsal striatal reactivity to negative outcomes

    Time frame: Up to 14 weeks after the baseline assessments.

    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.

  4. Decision uncertainty during approach-avoidance conflict decision making

    Time frame: Up to 14 weeks after the baseline assessments.

    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.

  5. Emotional conflict during approach-avoidance conflict decision making

    Time frame: Up to 14 weeks after the baseline assessments.

    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.

  6. Approach behavior during approach-avoidance conflict decision making

    Time frame: Up to 14 weeks after the baseline assessments.

    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.

  7. Bilateral amygdala volume

    Time frame: Up to 14 weeks after the baseline assessments.

    Gray matter volume of the bilateral amygdala

  8. Bilateral striatal volume

    Time frame: Up to 14 weeks after the baseline assessments.

    Gray matter volume of the bilateral striatum

  9. Bilateral hippocampal volume

    Time frame: Up to 14 weeks after the baseline assessments.

    Gray matter volume of the bilateral striatum

Study contacts

Contact information is provided by the study sponsor or research team.

Mallory Cannon, M.S.

CONTACT

[email protected]

918-581-4885

Robin L Aupperle, PhD

CONTACT

[email protected]

918-502-5744

Sponsors and collaborators

Lead sponsor

Laureate Institute for Brain Research, Inc.

Other

Collaborators

  • National Institute of Mental Health (NIMH)

Registry information

Official study title

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

Acronym: AAC-BeT

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
Jun 11, 2020
Registry last updated
Jun 13, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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