# Specifying and Treating the Anxiety Phenotype in Autism Spectrum Disorder

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $674,757

## Abstract

PROJECT SUMMARY – PROJECT 1 
Forty to eighty percent of children and preadolescents with autism spectrum disorder (ASD) exhibit clinically 
significant anxiety symptoms, which are associated with increased social deficits, depression, irritability, and 
stereotyped and self-injurious behaviors. While it is clear that anxiety symptoms represent a substantial problem 
for those with ASD, important issues that could inform treatment remain unresolved. For example: 1) there is a 
lack of clarity about how to differentiate ASD and anxiety symptoms, 2) little is known about how anxiety 
manifests in those with ASD and intellectual disability (ID), 3) the neural substrates of anxiety in ASD are poorly 
understood, and 4) it is unclear what treatment(s) to employ to help affected individuals given the early stage of 
research. In Project 1 of the Center for the Development of Phenotype-Based Treatments of Autism Spectrum 
Disorder, we conduct a comparative efficacy trial with neuroimaging in n=132 participants (ages 8-12 years) with 
ASD and clinically significant anxiety to resolve some of these issues. In Specific Aim 1, we attempt to better 
characterize the sub-group of children and preadolescents with ASD that exhibit anxiety. We use 
clinician-administered gold standard measurements as well as parent reports of overlapping constructs such as insistence 
on sameness, sensory processing issues, and emotion regulation problems that complicate the anxiety 
phenotype in ASD. We implement multivariate statistical analyses to reveal anxiety sub-types. We then examine 
whether anxiety prevalence estimates differ depending on whether clinician-administered or common parent 
questionnaires are used to see if the latter produce lower results for those with ASD and ID. In Specific Aim 2, 
we conduct a rigorous 16-week randomized, comparative treatment trial of a form of cognitive behavior therapy 
(CBT) called Behavioral Intervention for Anxiety in Children with Autism (BIACA), sertraline, and pill placebo in 
youth with ASD, IQ>50, and at least one clinically significant anxiety disorder. We compare the relative efficacy 
of: (1) BIACA vs. pill placebo and sertraline vs. pill placebo in reducing anxiety symptoms, (2) BIACA vs. pill 
placebo and sertraline vs. pill placebo in reducing the severity of ASD symptoms, and (3) BIACA vs. sertraline 
in reducing anxiety symptoms across sub-types. We predict that both therapies will be effective, but that BIACA 
will have advantages in treating ASD symptoms. In Specific Aim 3, we use fMRI to investigate neural predictors 
of treatment efficacy, markers of treatment-induced change, and signatures of the anxiety sub-types. Here, we 
hypothesize that reductions in anxiety scores during sertraline and BIACA treatment will be predicted by 
pre-treatment recruitment of the ventromedial and ventrolateral cortices, along with reduced task-based functional 
connectivity between these prefrontal regions and the amygdala during ...

## Key facts

- **NIH application ID:** 9984472
- **Project number:** 5P50HD093079-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** MARJORIE SOLOMON
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $674,757
- **Award type:** 5
- **Project period:** 2017-09-07 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984472

## Citation

> US National Institutes of Health, RePORTER application 9984472, Specifying and Treating the Anxiety Phenotype in Autism Spectrum Disorder (5P50HD093079-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984472. Licensed CC0.

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