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Toward Scalable Biomarker-Based Prediction of ASD in High-Risk Infants

Award Number: R01MH121462
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/16/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Toward Scalable Biomarker-Based Prediction of ASD in High-Risk Infants - ABSTRACT Despite tremendous effort by parents, researchers, clinicians, and educators, autism spectrum disorder (ASD) continues to present a significant, lifelong challenge to most affected individuals and their families. Studies of early development in infants at risk for ASD (such as infants with older siblings with ASD: “HR infant siblings” – who have a ~20% chance of developing ASD) can identify early, presymptomatic predictors of ASD that can then improve early screening and promote presymptomatic intervention. Behavioral studies of these HR infant siblings have identified atypical behaviors in the second year of life in the social domain, with some evidence of motor delays and differences in social attention within the first year. However, in part because of the limited behavioral repertoire of infants, investigators have struggled to identify consistent first-year-of-life behaviors that predict later ASD in a clinically actionable manner. We propose that the earliest measures of atypical development should directly assay brain function. The Infant Brain Imaging Study (IBIS) Network has used MRI methods to reveal functional and structural brain changes in the first year of life in HR infant siblings. These brain changes are present prior to the emergence of behavioral features of ASD and accurately predict ASD at 24 months of age (positive predictive value >= 80%). While scientifically promising, MRI's cost and reduced availability limit its potential scalability for use in HR infants to use as a general population screener in clinical settings. Electroencephalography (EEG) and eye tracking (ET) represent two scalable methods that can measure brain function and can help to identify predictive biomarkers of ASD in early infancy. EEG and ET are developmentally sensitive and accessible in community, real-world settings. In spring 2019, the Infant Brain Imaging Study (IBIS) Network will launch a new study of 250 HR infants designed to replicate and extend its predictive MRI findings. Here, we propose to add EEG and ET measures of brain function to this study, testing HR infants from IBIS at 6 and 12 months of age, and assessing clinical outcomes at 24 months of age with clinical outcomes assessed at 24 months of age. We will examine brain network function at rest, during low level sensory processing, and during social information processing. Our hypothesis is that these scalable EEG/ET biomarkers will (Aim 1) accurately identify infants with a later diagnosis of ASD and will (Aim 2) relate to ASD-associated behaviors at 24 months of age. Capitalizing on this unprecedented opportunity to integrate EEG/ET with neuroimaging in the same cohort of infants, in Aim 3 we also propose to explore the predictive power of these combined measures, and the association between EEG/ET and MRI features. The overarching goal of this proposal is to lower the age of detection of autism to early infancy, making intervention before the emergence of ASD-specific behavioral features feasible and more effective. Positive findings in the proposed study will also facilitate the future extension of presymptomatic predictive testing from HR infants to infants in the general population.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2023	CHILDREN'S HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Mental Health Research Grants	000	5	12/9/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $700,223 )
2023	2023	CHILDRENS HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Mental Health Research Grants	000	5	7/28/2023	NON-COMPETING CONTINUATION	$700,223
														Subtotal = $700,223

Issue Date FY: 2022 ( Subtotal = $749,394 )
2022	2022	CHILDRENS HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Mental Health Research Grants	003	4	8/27/2022	NON-COMPETING CONTINUATION	$749,394
2022	2021	CHILDRENS HOSPITAL LOS ANGELES	4650 SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Mental Health Research Grants	002	3	3/10/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2022	2021	CHILDRENS HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Mental Health Research Grants	001	3	2/28/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$674,554
2022	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	2	2/28/2022	NON-COMPETING CONTINUATION	-$674,554
														Subtotal = $749,394

Issue Date FY: 2021 ( Subtotal = $855,094 )
2021	2021	CHILDRENS HOSPITAL LOS ANGELES	4650 SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Mental Health Research Grants	002	3	9/25/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$77,085
2021	2021	CHILDRENS HOSPITAL LOS ANGELES	4650 SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Mental Health Research Grants	001	3	8/25/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$778,009
2021	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	2	8/25/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $855,094

Issue Date FY: 2020 ( Subtotal = $786,090 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	001	2	7/24/2020	NON-COMPETING CONTINUATION	$786,090
2020	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	000	1	2/27/2020	NEW	$0
														Subtotal = $786,090

Issue Date FY: 2019 ( Subtotal = $862,522 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	001	1	9/25/2019	NEW	$0
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	000	1	9/24/2019	NEW	$862,522
														Subtotal = $862,522

Grand Total All Awards = $3,953,323

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Toward Scalable Biomarker-Based Prediction of ASD in High-Risk Infants

Award Number: R01MH121462

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/16/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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