Hostile Interpretation Bias Training to Treat Irritability

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Neurocognitive Targets of Hostile Interpretation Bias Training to Treat Irritability

Conditions
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Irritable Mood, Mood Disorders

Intervention / Treatment
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* Device: IBT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adolescents in mental health treatment, with at least: mild, clinically significant irritability, and typical intellectual functioning (IQ>80) Exclusion Criteria: Any of the following mental health diagnoses: current post-traumatic stress lifetime bipolar I or II disorder lifetime cyclothymic disorder lifetime psychotic disorder lifetime autism spectrum disorder Major medical problems, including head trauma. MRI-specific safety exclusions for the MRI arms. Clinical instability.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 17 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active IBT, Out of MRI<br> | Device: IBT<br>* Interpretation bias training<br>|
| Sham Comparator: Sham IBT, Out of MRI<br> | Device: IBT<br>* Interpretation bias training<br>|
| Active Comparator: Active IBT, In MRI<br> | Device: IBT<br>* Interpretation bias training<br>|
| Sham Comparator: Sham IBT, In MRI<br> | Device: IBT<br>* Interpretation bias training<br>|

What is the study measuring?
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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 morphed images between happy=1 to angry=15 facial expressions. Lower indifference points indicate a higher bias towards hostile (or angry) judgments. Change in interpretation bias is the difference between the post- and pre-IBT indifference points. | 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 during the course of training. These fluctuations are expected to be significantly modulated by interpretation bias training. | 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. It measures the average trial-by-trial change in happy or angry judgments in response to feedback during a session of IBT. | During the course of the 1 day single interpretation bias training session. | 
| Irritability | Tendency towards anger and temper outburst as measured by the Affective Reactivity Index. | Within one week prior to Interpretation bias training and one week +/- 3 days after Interpretation bias training. |