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.

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.

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.

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.

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.

Within one week prior to Interpretation bias training and one week +/- 3 days after Interpretation bias training.

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.

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.

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.