Specifying and Treating Anxiety in Autism Research

Approximately 40%-80% of children and adolescents with autism spectrum disorder (ASD) exhibit clinically significant anxiety symptoms. These symptoms are associated with increased social deficits, depression, irritability, and stereotyped and self-injurious behaviors. Children and adolescents with anxiety also frequently avoid potentially stressful situations, thereby missing opportunities to learn important new skills. Despite the significant consequences of anxiety symptoms, what to do about this problem is less clear. The search for empirically-validated treatments has begun with multiple small trials providing promising evidence that selective serotonin reuptake inhibitors (SSRIs) and cognitive behavior therapy (CBT) might reduce anxiety in those with ASD. However, this work is in its early stages. There is a great need for large, rigorously designed trials that validate the effectiveness of both medication and CBT, as well as functional neuroimaging studies that identify neural predictors of treatment efficacy and markers of therapy-induced change. Such work holds the potential to help answer the questions posed above and to assist the field in developing more personalized treatments. In Project 1 of the Center for the Development of Phenotype-Based Treatments of Autism Spectrum Disorder, we conducted a study in children with ASD and clinically significant anxiety ages 8-14 to compare efficacy of these different treatment types. More specifically, the overall aim of the study was to conduct a 16-week randomized comparative treatment trial of Behavioral Intervention for Anxiety in Children with Autism (BIACA), sertraline, and placebo in youth with ASD, IQ (intelligence quotient) \>50, and clinically significant anxiety as assessed by a PARS score that is greater than or equal to 8. PARS is the primary outcome measures for the trial. Other prespecified measures such as clinician-administered gold standard assays will be used of traditional DSM (Diagnostic and Statistical Manual) \[Pediatric Anxiety Rating Scale (PARS) and the Anxiety Disorders Interview Schedule-IV (ADIS-IV)\], and nontraditional ASD related anxiety symptoms \[Autism Spectrum Addendum to the ADIS (ASDD)\] to qualify participants. We also used additional prespecified measures including parent reports of potentially overlapping symptoms that complicate the ASD anxiety phenotype. Although we additionally had wanted to include fMRI to investigate neural predictors of treatment efficacy, markers of treatment induced change, and signatures of anxiety sub-types, these efforts needed to be stopped due to the pandemic.