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Predicting the onset of depression in at-risk adolescents from endophenotype profiles

Award Number: R01MH116969
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/11/2018
PERIOD OF PERFORMANCE END DATE: 10/31/2025

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Predicting the onset of depression in at-risk adolescents from endophenotype profiles - Project Summary/Abstract Major depressive disorder (MDD) is uncommon in childhood, but becomes increasingly prevalent during adolescence. By the age of 18, about 15% of adolescents will have experienced at least one episode of MDD, with females twice as likely than males to have suffered an episode. This developmental surge in depression is especially high among teens who have a parent with a history of MDD, with close to half developing the disorder by the end of adolescence. Despite these epidemiological findings, and the range of negative downstream consequences linked to MDD, there are strikingly little data on the neural and behavioral abnormalities that confer risk for future depression onset in youth. The ability to prospectively predict MDD prior to its onset would have important clinical implications for the early identification of – and targeted deployment of interventions for – at-risk youth, which is strongly aligned with the NIMH Strategic Plan. To address these gaps, adolescents ages 12-15 at increased risk of MDD onset by virtue of a parental history of MDD, as well as a control sample with no parental history of depression, will complete baseline neural (fMRI) and behavioral assessments of replicated endophenotypes of MDD (neuroticism, anhedonia, cognitive control deficits). Growing evidence and our preliminary data suggest that these endophenotypes are relatively stable trait-like risk markers, have non-overlapping neural substrates, and precede and prospectively predict depression onset. The project has three aims. First, we will evaluate the neural correlates of these three endophenotypes in an adolescent sample (n = 148), half of whom are at elevated risk of MDD (Aim 1). Second, during a 24-month follow-up phase, participants will be contacted by phone every 6 months and administered measures to assess changes in symptoms. Analyses will test whether behavioral and neural endophenotype measures prospectively predict onset of depressive symptoms during the follow-up phase. Importantly, to evaluate incremental predictive validity, we will test whether each endophenotype measure predicts future depressive symptoms above and beyond relevant clinical, familial/demographic and developmental variables previously linked with risk of future depression (Aim 2). Third, we will test whether multivariate machine learning models incorporating behavioral and neural endophenotype markers, as well as clinical, familial/demographic, and developmental characteristics, can be used to predict subject-specific risk of future depression onset with sufficiently high sensitivity and specificity to be clinically useful (Aim 3). Critically, recent advances in machine learning allow for the development of algorithms predicting risk at the individual level, as well as the integration of numerous predictors rather than relying on single variables that may, in isolation, have limited clinically-useful predictive value. Collectively, results are expected to advance our ability to predict the onset of depressive symptoms and, ultimately, to inform the development of a freely available, web-based risk calculator for predicting subject-specific depression risk.


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 = $0 )
2025	2024	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	5	10/23/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $544,282 )
2024	2024	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	5	12/4/2023	NON-COMPETING CONTINUATION	$489,856
2024	2024	THE MCLEAN HOSPITAL CORPORATION	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	001	5	8/15/2024	NON-COMPETING CONTINUATION	$54,426
														Subtotal = $544,282

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	4	12/1/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $592,827 )
2022	2022	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	001	4	5/16/2022	NON-COMPETING CONTINUATION	$59,283
2022	2022	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	4	11/1/2021	NON-COMPETING CONTINUATION	$533,544
														Subtotal = $592,827

Issue Date FY: 2021 ( Subtotal = $532,914 )
2021	2021	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	001	3	4/14/2021	NON-COMPETING CONTINUATION	$53,292
2021	2021	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	3	10/29/2020	NON-COMPETING CONTINUATION	$479,622
														Subtotal = $532,914

Issue Date FY: 2020 ( Subtotal = $563,046 )
2020	2020	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	001	2	2/3/2020	NON-COMPETING CONTINUATION	$56,305
2020	2020	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	2	11/5/2019	NON-COMPETING CONTINUATION	$506,741
														Subtotal = $563,046

Issue Date FY: 2019 ( Subtotal = $584,268 )
2019	2019	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	001	1	9/24/2019	NEW	$0
2019	2019	MCLEAN HOSPITAL CORPORATION, THE	115 MILL ST	BELMONT	MA	02478	MIDDLESEX	USA	Mental Health Research Grants	000	1	12/11/2018	NEW	$584,268
														Subtotal = $584,268

Grand Total All Awards = $2,817,337

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Predicting the onset of depression in at-risk adolescents from endophenotype profiles

Award Number: R01MH116969

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/11/2018

PERIOD OF PERFORMANCE END DATE: 10/31/2025

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