# Heterogeneity in Autism Spectrum Disorders: Biological Mechanisms, Trajectories, and Treatment Response

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $2,126,237

## Abstract

This application seeks to renew our highly productive and interdisciplinary UCLA Autism Center of
Excellence (ACE III). Over the last decade, our group has made significant advances in the field, identifying
risk genes, candidate brain based biomarkers of treatment response and early risk markers of Autism
Spectrum Disorder (ASD) beginning in the first few weeks of life. We developed new interventions for toddlers
with social communication delays, identified an intervention with the most robust effects on repetitive behaviors
to date, and we showed how genetic risk influences brain structure and function in ASD. Most unique and
impactful is our Center's integration of genetics, early biomarkers and behavioral assays with intervention
 In parallel with growing awareness in the field, we recognize the profound clinical and genetic heterogeneity
in ASD, which poses a significant challenge to identifying diagnostic biomarkers and to developing effective
interventions that target individual profiles. In order to move from a “one size fits all” to a “precision medicine”
approach, we must better understand the biological and clinical basis of this heterogeneity. Our ACE
application takes a multidisciplinary, integrative approach to study the relationship between genetic, neural and
phenotypic heterogeneity in ASD, to determine whether this heterogeneity reflects unique biological
mechanisms underlying autism, and to identify predictors of developmental trajectories and treatment
outcome. In four interacting projects, we will focus on three areas of heterogeneity that our work suggests has
unique neural, genetic and behavioral signatures: sensorimotor processing social attention/motivation, and
social communication/language. Project I aims to determine how differences in genetic risk for autism (familial
risk, 22q11deletion, and Tuberous Sclerosis Complex (TSC) affect early brain development, neuroimaging and
EEG biomarkers in the first year of life and identifying predictors of ASD diagnosis at age 3; P. II examines
heterogeneity in treatment response using a SMART design, 3-phase adaptive treatment intervention for very
young children at risk for ASD; P. III uses MRI in youth with ASD to determine how behavioral phenotypes and
genetic risk differentially affect brain activation, structural and functional connectivity. P. IV conducts a proof-of-
mechanism pharmacological trial aimed to increase social interest and social reward responsivity with the
dopamine precursor L-DOPA in adolescents and young adults enrolled in a social skills intervention.. All
projects examine these target phenotypes using at least one biological marker, in addition to standardized and
observational tests. This will allow us to integrate biomarkers, genetics and behavior across projects and
across ages. A well-established core infrastructure centralizes diagnostics, genetics, imaging, and EEG
acquisition, with a common database built for cross project and core collaboration, an...

## Key facts

- **NIH application ID:** 9984490
- **Project number:** 5P50HD055784-14
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** SUSAN Y BOOKHEIMER
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,126,237
- **Award type:** 5
- **Project period:** 2007-08-06 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984490

## Citation

> US National Institutes of Health, RePORTER application 9984490, Heterogeneity in Autism Spectrum Disorders: Biological Mechanisms, Trajectories, and Treatment Response (5P50HD055784-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984490. Licensed CC0.

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