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Childhood adversity, DNA methylation, and psychopathology symptoms: A longitudinal study of sensitive periods and chrono-epigenetics

Award Number: R01MH113930
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary. Childhood adversity is a potent risk factor for depression, increasing lifetime risk of this common and burdensome disorder by at least two-fold. While the association between adversity and depression is well documented, the mechanisms explaining this relationship are poorly understood. In a BRAINS R01 award, we made several new discoveries about how childhood adversity could become biologically embedded to shape depression risk through DNA methylation (DNAm), a major type of epigenetic modification. We showed that DNAm associations with adversity may not merely be molecular records of adversity exposure, but rather, possibly function as a biological mediator linking childhood adversity to depression risk. We also identified potential sensitive periods after birth and in the first five years of postnatal life when adversity exposure imparted more enduring effects on the epigenome and in shaping depression risk. However, these analyses were limited to mostly European-ancestry samples of children with low/moderate adversity exposure and only 2 time points of blood DNAm. In this renewal, we build on our prior work by exploring these relationships in a population-based longitudinal sample of children in South Africa, who are part of the Drakenstein Child Health Study (DCHS). Relative to our prior work and the field of epigenetics at large, the DCHS birth cohort provides an unprecedented opportunity to study these associations within an established group of more racially/ethnically diverse children, many of whom have experienced considerable early adversity directly or indirectly through their families own exposure. We will capitalize on existing, repeated adversity markers collected by the DCHS during early childhood and derive epigenetic data from stored blood samples collected at ages 1, 3, and 5. With these rich longitudinal data, we will identify the genetic and social drivers and outcomes of chrono-epigenetics, a newly coined term to describe the temporal dynamics of epigenetic processes, across the early life course. In Aim 1, we will characterize the effects of genotype on DNAm levels at specific ages and DNAm trajectories across time. In Aim 2, we will investigate the role of repeated adversity exposure measures before age 5 on DNAm patterns using a two-stage structured life-course modeling approach that our interdisciplinary team developed for high-dimensional epigenetic analyses. In Aim 3, we will use statistical mediation and causal inference approaches (e.g., Mendelian Randomization) to evaluate the extent to which these DNAm patterns explain the relationship between adversity timing and children’s internalizing symptoms at age 8, one of the earliest signs of depression risk. In sum, this renewal project will identify specific genetic and social factors shaping DNAm patterns, determine the ages when adversity is most likely to affect this biomarker, and generate biological insights that may lead to new intervention strategies to prevent depression, ensuring these findings apply to diverse samples of youth.


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: 2024 ( Subtotal = $718,059 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	8	3/4/2024	NON-COMPETING CONTINUATION	$718,059
														Subtotal = $718,059

Issue Date FY: 2023 ( Subtotal = $653,676 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	001	7	6/15/2023	NON-COMPETING CONTINUATION	$653,676
2023	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	6	10/17/2022	COMPETING CONTINUATION	$0
														Subtotal = $653,676

Issue Date FY: 2022 ( Subtotal = $670,300 )
2022	2022	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	003	6	8/23/2022	COMPETING CONTINUATION	$280,753
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	001	6	4/5/2022	COMPETING CONTINUATION	$670,300
2022	2021	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	002	5	8/23/2022	NON-COMPETING CONTINUATION	-$280,753
2022	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	5	4/5/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $670,300

Issue Date FY: 2021 ( Subtotal = $529,997 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	5	3/22/2021	NON-COMPETING CONTINUATION	$529,997
														Subtotal = $529,997

Issue Date FY: 2020 ( Subtotal = $539,041 )
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	4	3/12/2020	NON-COMPETING CONTINUATION	$539,041
														Subtotal = $539,041

Issue Date FY: 2019 ( Subtotal = $720,631 )
2019	2019	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	3	3/13/2019	NON-COMPETING CONTINUATION	$543,690
2019	2019	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	001	3	6/12/2019	SUPPLEMENT FOR EXPANSION	$176,941
														Subtotal = $720,631

Issue Date FY: 2018 ( Subtotal = $566,206 )
2018	2018	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	001	2	6/1/2018	NON-COMPETING CONTINUATION	$56,621
2018	2018	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	2	3/2/2018	NON-COMPETING CONTINUATION	$509,585
														Subtotal = $566,206

Issue Date FY: 2017 ( Subtotal = $518,628 )
2017	2017	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	1	7/18/2017	NEW	$518,628
														Subtotal = $518,628

Grand Total All Awards = $4,916,538

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Childhood adversity, DNA methylation, and psychopathology symptoms: A longitudinal study of sensitive periods and chrono-epigenetics

Award Number: R01MH113930

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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