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Epigenetic biomarkers for the risk and progression of depression among young adolescents

Award Number: R21MH141701
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/10/2026
PERIOD OF PERFORMANCE END DATE: 08/09/2028

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Epigenetic biomarkers for the risk and progression of depression among young adolescents - Project Summary Adolescent internalizing problems—including anxiety, withdrawal, and depression—present an urgent public health concern, affecting a substantial proportion of U.S. adolescents aged 12-17. Early life stress (ELS), such as childhood adversity and trauma, amplifies the risk of developing internalizing problems, with affected children having approximately 2.5 times higher odds than peers without such experiences. Although the effects of ELS may not be immediately apparent, they can have a lasting impact on long-term quality of life, underscoring the importance of early identification of at-risk individuals. DNA methylation (DNAm) and microRNA (miRNA) expression regulate gene activity in response to environmental stress. While previous studies suggest that DNAm changes during childhood and adolescence are linked to mental health outcomes, large-scale validation in long-term, population-based cohorts remain a critical gap. Similarly, miRNAs, which regulate gene expression and play a pivotal role in stress responses, are underexplored in human studies linking ELS to internalizing problems. This project aims to identify epigenetic biomarkers—specifically miRNAs and DNAm—that mediate the effects of ELS on adolescent internalizing problems. We hypothesize that miRNA expression, in combination with DNAm, serves as a powerful, synergistic predictor of internalizing problems. To test this, we will apply advanced computational techniques, including longitudinal mediation analysis and machine learning, utilizing data from two robust, long-term population-based cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC) and Generation R. Our specific aims are: (1) Investigate the impact of dynamic changes in DNAm on the risk of internalizing problems, with a focus on individual-level variability and the role of ELS; (2) Identify the link between ELS, miRNA expression, and internalizing problems; and (3) Estimate the synergistic contribution of DNAm and miRNAs in predicting internalizing problems through the creation of a composite epigenetic risk score. By integrating multi-omics data and leveraging extensive follow- up from birth through adolescence, this project will offer groundbreaking insights into how ELS shapes the biological risk for internalizing problems. These findings will significantly enhance our ability to detect early biomarkers of internalizing difficulties, paving the way for tailored, preventive interventions aimed at reducing the burden of adolescent internalizing problems.


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 = $418,000 )
2026	2026	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Mental Health Research Grants	000	1	8/12/2026	NEW	$418,000
														Subtotal = $418,000

Grand Total All Awards = $418,000

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Epigenetic biomarkers for the risk and progression of depression among young adolescents

Award Number: R21MH141701

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/10/2026

PERIOD OF PERFORMANCE END DATE: 08/09/2028

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