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Variation in early motor function in autism, cerebellar injury and normal twins

Award Number: R01MH123723
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Variation in early motor function in autism, cerebellar injury and normal twins - Project Summary Autism spectrum disorder (ASD) is one of the most common and highly inherited of all developmental disorders, with heritability exceeding 0.80. Although remarkable advances in genetics have identified rare de novo mutations in select brain genes, by definition, none of these relate to the pronounced heritability of autism relevant to the vast proportion of cases in the population. Given that heritability has been shown to be a function of additive genetic risk, inferring an impractically large number of genetic targets for intervention, an important strategy is to identify convergent mechanisms of polygenic risk factors by elucidating intermediate phenotypes (i.e., endophenotypes) through which they exert their causal influence. Our group has identified two such candidates that appear highly contributory but not sufficient for ASD: (i) the social behavioral phenotype indexed by quantitative (subclinical) autistic traits in parents (QAT-p); and (ii) variation in social visual engagement (SVE), an eye-tracking measure based on viewing of dynamic social scenes. Both can be ascertained in the first year of life using rapid acquisition methods of less than 20 minutes. Our team’s prior work strongly supports a developmental model in which autism arises from joint additive genetic effects of these and other neurodevelopmental liabilities, suggesting that targeting a discrete group of early-contributing liabilities before autism develops offers the greatest opportunity for high-impact, personalized intervention for children at risk for common, polygenic forms of ASD. The primary objective of this research program is to validate wearable-sensor methodology (bilateral, wrist-worn accelerometers) for quantifying two additional endophenotypes: hyperactivity (HYP, as an early marker of liability to Attention Deficit Hyperactivity Disorder, which is strongly comorbid with autism) and impairment in motor coordination (MOT). We will examine HYP and MOT in three distinct samples. Aim I will study 120 pairs of infant twins first assessed at 6 months of age and then followed at ages 18 and 36 months to evaluate early associations between HYP, MOT, QAT, and SVE, as well as their heritability and ability to predict quantitative variation in autistic traits among the twins. Aim II will study a cohort of 50 toddlers diagnosed with idiopathic ASD to determine whether novel sensor-based metrics of HYP and MOT show differences between the twins and children with ASD. Aim III will study a legacy cohort of 120 infants at elevated risk for autism due to prematurity and/or cerebellar injury, in whom we will explore relationships between cerebellar structure and function in the first year of life and a) sensor-based indices of HYP and MOT, b) quantitative autistic traits, and c) performance-based indices of motor ability at age three years. This project is expected to yield a rich, comprehensive understanding of motor endophenotypes in infants and children and their contributions to autism, with the eventual goal of providing a launching point for future screening and early intervention studies in high-risk children.


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	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	5	12/5/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $577,990 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	5	2/19/2025	NON-COMPETING CONTINUATION	$577,990
														Subtotal = $577,990

Issue Date FY: 2024 ( Subtotal = $717,271 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	001	4	8/14/2024	NON-COMPETING CONTINUATION	$71,727
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	000	4	2/14/2024	NON-COMPETING CONTINUATION	$645,544
														Subtotal = $717,271

Issue Date FY: 2023 ( Subtotal = $671,023 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	3	2/21/2023	NON-COMPETING CONTINUATION	$671,023
														Subtotal = $671,023

Issue Date FY: 2022 ( Subtotal = $727,384 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	001	2	6/7/2022	NON-COMPETING CONTINUATION	$72,740
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	2	3/1/2022	NON-COMPETING CONTINUATION	$654,644
														Subtotal = $727,384

Issue Date FY: 2021 ( Subtotal = $857,745 )
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	1	4/12/2021	NEW	$777,720
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	001	1	5/4/2021	NEW	$80,025
														Subtotal = $857,745

Grand Total All Awards = $3,551,413

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Variation in early motor function in autism, cerebellar injury and normal twins

Award Number: R01MH123723

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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