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Alignment of cortical development trajectories with emergent dimensional psychopathology and related risk factors among adolescents in the ABCD Study

Award Number: R01MH124694
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Alignment of cortical development trajectories with emergent dimensional psychopathology and related risk factors among adolescents in the ABCD Study - PROJECT SUMMARY Efforts to discover biological signatures for mental illness focus increasingly on adolescence, a period of rapid brain development that immediately precedes the peak age of onset for many disorders. Maturation of the cerebral cortex during this time has long been thought to mediate emergence of early symptoms. The ongoing Adolescent Brain Cognitive Development (ABCD) Study provides an unprecedented opportunity to align emergence of psychopathology with specific changes in cortical maturation within a diverse population of nearly 12,000 youth. Enrolled at age 9-10, participants are being studied with 6 standardized MRI assessments over a 10 year period, along with developmental history, genotype, and annual measures of dimensional symptoms and of their home, school, and social environment. This application seeks to renew an R01 grant that is focused on eliciting cortical developmental signatures of emergent psychopathology in ABCD and triangulating these signatures with causal genomic and environmental risk factors. The award period coincides with the second half of the ABCD Study (ages 14-20), and we will use publicly available data from annual releases to test our hypotheses. Supported by findings from the first award period, our central scientific premise is that (1) variance in late cortical thinning, as it proceeds along anterior and lateral brain territory, will predict emergent psychopathology in late adolescence; and (2) progressive associations between thinning and emergent symptoms will reflect a gradient of temporally distal (prenatal) to proximal (postnatal) risk factors. Aim 1 will ultimately use all 6 biennial measures of cortical thickness and annual measures of dimensional psychopathology from ages 9 to 20, enabling precise temporal and spatial alignment of cortical maturation and symptom emergence. Aim 2 will consider this alignment within the frame of available postmortem transcriptomic data, to assess the contributions of polygenic risk scores and temporospatial gene co- expression programs from pre- and postnatal periods. Aim 3 will focus on pre- and postnatal environmental risk factors, and will determine whether prenatal adversity and disruptions related to the Covid-19 pandemic shape relationships between cortical thinning and emergent psychopathology. These analyses will be supported by new methods that we developed during the last award period, including a rigorous quality control pipeline for reducing measurement errors in structural MRI studies of children, and a novel method of parsing polygenic risk based on pre- versus postnatal gene expression. By the conclusion of the proposed studies we will establish specific cortical signatures that bridge causal factors with emergent psychopathology in adolescence, and that can be leveraged for early recognition and intervention studies.


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: 2025 ( Subtotal = $428,400 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	001	6	3/28/2025	COMPETING CONTINUATION	$428,400
2025	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	5	3/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $428,400

Issue Date FY: 2024 ( Subtotal = $420,000 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	5	8/24/2024	NON-COMPETING CONTINUATION	$420,000
														Subtotal = $420,000

Issue Date FY: 2023 ( Subtotal = $420,000 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	4	8/10/2023	NON-COMPETING CONTINUATION	$420,000
														Subtotal = $420,000

Issue Date FY: 2022 ( Subtotal = $420,000 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	3	8/1/2022	NON-COMPETING CONTINUATION	$420,000
														Subtotal = $420,000

Issue Date FY: 2021 ( Subtotal = $420,000 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	2	8/20/2021	NON-COMPETING CONTINUATION	$420,000
														Subtotal = $420,000

Issue Date FY: 2020 ( Subtotal = $413,200 )
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	1	9/11/2020	NEW	$413,200
														Subtotal = $413,200

Grand Total All Awards = $2,521,600

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Alignment of cortical development trajectories with emergent dimensional psychopathology and related risk factors among adolescents in the ABCD Study

Award Number: R01MH124694

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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