Effects of a Novel Behavioral Intervention for Irritability in Autism on Neural Circuitry of Emotion Regulation

Background: Approximately 50 percent of children with autism spectrum disorder (ASD) exhibit irritability and disruptive behaviors such as tantrums, noncompliance, and aggression. If present in childhood, aggression tends to persist into adulthood and contribute to disability over and above the core autism symptoms. The atypical antipsychotics risperidone and aripiprazole are approved for aggression in ASD but they are associated with weight gain and other adverse effects.  Parent training and applied behavioral analysis interventions for aggression in autism have been studied in young children but not in adolescents with high-functioning ASD.

Objectives: The objectives of this study were to test whether behavioral intervention for irritability in autism would engage neural targets within the circuitry of emotion regulation. Methods: Based on our work on cognitive-behavioral therapy and parent management training for disruptive behavior, we developed a new intervention, comprehensive behavior therapy for irritability and aggression (BTIA) for adolescents with autism. We piloted BTIA with eight adolescents with ASD and high levels of aggressive behavior.

Results: Subjects included seven boys and one girl with ASD, mean age=14.3+1.4 and mean IQ=94.6+12.8. Six subjects were receiving medication (aripiprazole, citalopram, quetiapine, atomoxitine, and sertraline) that had been stable for at least six weeks prior to initiating BTIA and remained stable during the study. Participants showed a significant reduction in aggressive behavior with a 12-point change in the mean ABC irritability score from baseline to endpoint (paired samples t=10.6, p<0.01). The 12-point reduction in the ABC irritability score is a clinically meaningful change and it is similar to the mean improvement in the RUPP trial of risperidone (Research Units on Psychopharmacological Interventions in Autism Network, 2002). We also collected fMRI data during the frustration-induction GoNoGo task before and after treatment in four of eight children who participated in the CBT pilot. Regions-of-Interest analysis of the fMRI data was conducted using the independently-defined ROIs that were modulated by the task in an earlier study (Perlman and Pelphrey, 2010). There was an increase of activation in the right ventrolateral PFC in the recovery from frustration versus winning contrast from pre- to post-treatment. There were also increased levels of activation from pre- to post-treatment in the dorsal ACC, dorsomedial PFC, and right inferior frontal gyrus, and decreased activation in the right amygdala. The magnitude of the effects of BTIA on the levels of BOLD activation calculated as the Cohen’s d effect size for the difference in post- to pre-treatment activation divided by the pooled standard deviation ranged from 0.64 to 1.1, indicating moderate to large effect sizes.  

Conclusions: These results demonstrate that the BTIA can engage the neural circuitry of emotion regulation in children with ASD complicated by irritable and aggressive behavior. Larger, randomized controls studies are needed to confirm these findings.