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

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

• 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]
• Quinolinic Acid [Time frame: Up to 18 weeks after the baseline assessments]

Secondary outcome measures (6)

• Sheehan Disability 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 [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 [Time frame: Up to 18 weeks after the baseline assessments]
• Kynurenic acid [Time frame: Up to 14 weeks after the baseline assessments]
• Ratio of kynurenic acid to quinolinic acid [Time frame: Up to 14 weeks after the baseline assessments]
• Ratio of kynurenic acid to tryptophan [Time frame: Up to 18 weeks after the baseline assessments]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Basic science

Study locations

United States · 1 center

• Laureate Institute for Brain Research — Tulsa

Publications

• 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/s1306 PMID 31907032
• 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. PMID 25224633

Identifiers

NCT: NCT04426461 · 2020-003 · R01MH123691

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗