An Open Pilot Study of Training Hostile Interpretation Bias to Treat Disruptive Mood Dysregulation Disorder

Abstract

Objective: Irritability in disruptive mood dysregulation disorder (DMDD) may be associated with a biased tendency to judge ambiguous facial expressions as angry. We conducted three experiments to explore this bias as a treatment target. We tested: 1) whether youth with DMDD express this bias; 2) whether judgment of ambiguous faces can be altered in healthy youth by training; and 3) whether such training in youth with DMDD is associated with reduced irritability and associated changes in brain function.

Methods: Participants in all experiments made happy versus angry judgments of faces that varied along a happy to angry continuum. These judgments were used to quantify a "balance point," the facial expression at which a participant's judgment switches from predominantly happy to predominantly angry. We first compared balance points in youth with DMDD (n = 63) versus healthy youth (n = 26). We then conducted a double-blind, randomized controlled trial of active versus sham balance-point training in 19 healthy youth. Finally, we piloted open, active balance-point training in 14 youth with DMDD, with 10 completing an implicit functional MRI (fMRI) face-emotion processing task.

Results: Relative to healthy youth, DMDD youth manifested a shifted balance point, expressed as a tendency to classify ambiguous faces as angry rather than happy. In both healthy and DMDD youth, active training is associated with a shift in balance point toward more happy judgments. In DMDD, evidence suggests that active training may be associated with decreased irritability and changes in activation in the lateral orbitofrontal cortex.

Conclusions: These results set the stage for further research on computer-based treatment targeting interpretation bias of angry faces in DMDD. Such treatment may decrease irritability and alter neural responses to subtle expressions of happiness and anger.

Trial registration: ClinicalTrials.gov NCT00006177 NCT00025935.

FIG. 1.

The procedure for a single training session. Training is designed to shift interpretation of ambiguous morphs bias toward happy judgments. There are two types of blocks: Assessment blocks determine balance point and training blocks shift balance point toward more happy judgments. Seven of 15 morphs are displayed here. Subjects see them in random order, but here, for presentation purposes, they are shown along a continuum of happy to angry. The balance point (i.e., the morph at which judgments switch from predominantly happy to predominantly angry) is measured during assessment blocks. During active training, feedback is given after each response. The feedback threshold is the baseline balance point, measured during the first assessment block, shifted two morphs toward the angry end of the continuum. In sham training, the feedback threshold is the same as the baseline balance point. A color version of this figure is available in the online article at www.liebertpub.com/cap

FIG. 2.

Relative to healthy volunteer (HV) youth (n = 26), disruptive mood dysregulation disorder (DMDD) youth (n = 63) have a bias toward judging ambiguous morphs as angry for the male face in the upper right panel (p < 0.001). Mean proportions of angry responses are plotted against facial morphs, ordered from happy to angry. For each group, solid lines represent the fitted four parameter logistic curves. A DMDD bias toward judging ambiguous morphs as angry is indicated by a leftward shift of the red curve relative to the black curve. Note that judgments differ by face-identity. Ethnicity descriptions and pictures of each actor can be found at http://www.macbrain.org (Tottenham et al. 2009). Probability values are of balance point difference between the curves. A color version of this figure is available in the online article at www.liebertpub.com/cap

FIG. 3.

Interaction plot of active (n = 8) versus sham (n = 11) double- blind, randomized controlled trial of training in healthy volunteer (HV) youth. Asterisks represent p < 0.01 from the linear mixed-effects model parameter estimate t tests between the two groups at the sessions indicated. Error bars show standard error.

FIG. 4.

Disruptive mood dysregulation disorder (DMDD) youth (n = 14) responded to four daily sessions of training toward happy judgments of ambiguous faces, reflected by increasing balance points, decreased parent-report irritability (Affective Reactivity Index [ARI]), and clinical improvement (mean Clinical Global Impressions-Improvement [CGI-I] scores <5). For balance point and parent-report ARI, asterisks indicate p values for posttraining assessment versus initial parameter estimates. For CGI-I, asterisks indicate p values of t tests versus a score of 5, which indicates no improvement. *p < 0.05, **p < 0.01, error bars show standard error.

FIG. 5.

An increased bias toward happy judgments after training may be associated with reduced irritability and irritability-related clinical improvement in 14 youth with disruptive mood dysregulation disorder (DMDD). Blue trend lines are from outlier resistant “robust regression,” using reweighted least squares regression. The red line at a score of 5 in the Clinical Global Impressions-Improvement (CGI-I) corresponds to no clinical improvement, values <5 indicate improvement, and values >5 indicate clinical worsening. Insets contain Spearman's correlation coefficients and uncorrected p values. A color version of this figure is available in the online article at www.liebertpub.com/cap

FIG. 6.

Interpretation bias training is associated with increased neural activity in response to subtle expressions of happiness, relative to anger, in the bilateral orbitofrontal cortex (OFC) and left amygdala. The brain image shows the four regions of interest (ROIs) (lateral OFCs and amygdalae) that were examined. Bar charts indicate mean % blood–oxygen-level dependent (BOLD) signal change to each 50% emotion-neutral facial morph, relative to a fixation cross, measured before (solid bars) and after (striped bars) four sessions of daily training. Asterisks represent p values for the pre-versus posttraining, angry versus happy contrast parameter estimates. p < 0.1, *p < 0.05, **p < 0.01. A color version of this figure is available in the online article at www.liebertpub.com/cap