Hostile Interpretation Bias Training to Treat Irritability

Neurocognitive Targets of Hostile Interpretation Bias Training to Treat Irritability

Hostile interpretation bias may be a feature of severe, chronic irritability in children, one of the most common psychiatric symptoms of childhood. Interpretation bias training (IBT) is a computer-based training program that may reduce irritability in youths. This trial lays the groundwork for a test IBT on irritability.

Study Overview

• Status: Completed
• Conditions: Mood Disorders; Irritable Mood
• Intervention / Treatment: Device: IBT

Detailed Description

This trial lays the foundation for a preliminary test of efficacy of IBT on irritability by establishing IBT's neurocognitive treatment targets: hostile interpretation bias and response in the neural threat-learning system.

The design is a single-blinded, randomized controlled trial of IBT on its targets. The study will have four arms, with 25 participants in each arm for all four conditions of training (active versus sham) and scanning (in MRI or out of MRI scanner). During IBT, participants judge as happy or angry facial expressions which are on a continuum between happy and angry. The point at which judgments shift from predominantly happy to angry on this continuum is the indifference point. During training feedback encourages no change in the indifference point or a change in the indifference point towards more happy judgments of ambiguous faces. A shift in indifference point towards more benign judgments is interpreted as a reduction in hostile interpretation.

The design will test whether active relative to sham IBT shifts the indifference point towards more benign judgments. Neural response to active versus sham IBT will be measured in half the sample.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joel Stoddard, MD; Phone Number: 720-777-5702; Email: joel.stoddard@ucdenver.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adolescents in mental health treatment, with at least:

  1. mild, clinically significant irritability, and
  2. typical intellectual functioning (IQ>80)

Exclusion Criteria:

• Any of the following mental health diagnoses:

  1. current post-traumatic stress
  2. lifetime bipolar I or II disorder
  3. lifetime cyclothymic disorder
  4. lifetime psychotic disorder
  5. lifetime autism spectrum disorder
• Major medical problems, including head trauma.
• MRI-specific safety exclusions for the MRI arms.
• Clinical instability.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active IBT, Out of MRI; Interpretation bias training where participants learn more positive judgements of ambiguous facial expressions relative to their own baseline bias. This arm is completed in the clinic.	Device: IBT; Interpretation bias training
Sham Comparator: Sham IBT, Out of MRI; Interpretation bias training where participants' baseline judgements of ambiguous facial expressions is reinforced. This arm is completed in the clinic.	Device: IBT; Interpretation bias training
Active Comparator: Active IBT, In MRI; Interpretation bias training where participants learn more positive judgements of ambiguous facial expressions relative to their own baseline judgments. This arm is completed in a magnetic resonance imaging machine.	Device: IBT; Interpretation bias training
Sham Comparator: Sham IBT, In MRI; Interpretation bias training where participants' baseline judgements of ambiguous facial expressions is reinforced. This arm is completed in a magnetic resonance imaging machine.	Device: IBT; Interpretation bias training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Interpretation Bias	Interpretation bias is measured by the indifference point of happy-angry judgments of a continuum of 15 images of face emotion expression that are morphed between completely happy=1 to completely angry=15 facial expressions. Indifference point is represented on this scale of 1 to 15 faces. It represents the point on the face continuum where judgements change from predominantly happy to predominantly angry. Indifference points have a minimum value of 1 and a maximum value of 15, though are typically in the middle of the face-emotion continuum, e.g. 7. Lower indifference points represent a higher bias towards hostile (or angry) judgments. Change in interpretation bias is the difference between the post- and pre-training indifference points. This can range from -14 to 14, with positive numbers reflecting the degree to which the happy/angry decision bias is shifted towards more happy judgements. High positive numbers reflect a greater increase in happy judgments.	Up to one day before and after the single 1 day training session of Interpretation bias training session.
Neural Response in Threat Learning System.	Amygdala functional connectivity to ventromedial prefrontal cortex is measured by covariance in fluctuations in blood oxygen-level dependent signal between these regions during functional magnetic resonance imaging (fMRI) during the course of training. The outcome measure is a count of these randomized participants for whom the fMRI measure is valid for the planned connectivity analysis. These participants completed the task in scanner with acceptable behavioral data and fMRI data. Quality control for fMRI included visual inspection of brain images for quality, coverage, and proper alignment across functional, anatomic and template images. The fMRI images passed analysis benchmarks of <20% censored volumes and <0.25 mm Euclidean distance average censored motion across the task. Censor thresholds are 0.3 mm Euclidean distance and 5% voxels with outlying intensity values.	During the course of the 1 day single session of interpretation bias training session.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Learning Rate	Learning rate as measured by a reinforcement learning computational model during IBT, please see the reference Stoddard et al., 2023, for model details. As in general reinforcement learning models, it is the proportion of prediction error that is applied to future expectations. In this trial, when a participant received feedback about a judgement they made of a face, the participant implicitly compares that feedback to their expectations about that face. The difference between the feedback and their expectations is called prediction error. The learning rate the proportion of this prediction error that is applied to future expectations across the learning session. In that way it represents learning. Learning rate is a continuous, unitless value. It ranges from 0, representing no learning, to 1, representing perfect learning. It is generally small. The learning rate reported here is its form estimated across face emotions (see Stoddard et al., 2023).	During the course of the 1 day single interpretation bias training session.
Irritability	Irritability is the tendency towards anger and temper outburst as measured by the Affective Reactivity Index, a seven item scale. Each item has 3 response options which are coded as follows: "not true"=0, "somewhat true"=1, and "certainly true"=2. The first six items are summed to generate a total score that reflects the degree over irritability over the past week. The Affective Reactivity Index ranges from 0 to 12. Higher values reflect more irritability. What is reported here is the average post- minus pre-treatment score, by parent report. In these differences, negative values are in the unit of this scale and the absolute value represents the degree of irritability reduction.	Within one week prior to Interpretation bias training and one week +/- 3 days after Interpretation bias training.

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Joel Stoddard, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• Stoddard J, Sharif-Askary B, Harkins EA, Frank HR, Brotman MA, Penton-Voak IS, Maoz K, Bar-Haim Y, Munafo M, Pine DS, Leibenluft E. An Open Pilot Study of Training Hostile Interpretation Bias to Treat Disruptive Mood Dysregulation Disorder. J Child Adolesc Psychopharmacol. 2016 Feb;26(1):49-57. doi: 10.1089/cap.2015.0100. Epub 2016 Jan 8.
• Haller SP, Stoddard J, Botz-Zapp C, Clayton M, MacGillivray C, Perhamus G, Stiles K, Kircanski K, Penton-Voak IS, Bar-Haim Y, Munafo M, Towbin KE, Brotman MA. A Randomized Controlled Trial of Computerized Interpretation Bias Training for Disruptive Mood Dysregulation Disorder: A Fast-Fail Study. J Am Acad Child Adolesc Psychiatry. 2022 Jan;61(1):37-45. doi: 10.1016/j.jaac.2021.05.022. Epub 2021 Jun 17.
• Stoddard J, Haller SP, Costa V, Brotman MA, Jones M. A Computational Model Reveals Learning Dynamics During Interpretation Bias Training With Clinical Applications. Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Oct;8(10):1033-1040. doi: 10.1016/j.bpsc.2023.03.013. Epub 2023 Apr 14.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2018
• Primary Completion (Actual): January 27, 2023
• Study Completion (Actual): January 27, 2023

Study Registration Dates

• First Submitted: June 26, 2018
• First Submitted That Met QC Criteria: July 18, 2018
• First Posted (Actual): July 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders
• Other Study ID Numbers: 17-0464

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: A commitment to data sharing and analytic code has been made. Specifics of the data sharing plan require further work due to the collection of protected health information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No