Tuesday, July 1, 2025 7/1/2025

Neural mechanisms of risk for irritability across the transition to adolescence

Award Number: R01MH122487
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/03/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Neural mechanisms of risk for irritability across the transition to adolescence - PROJECT SUMMARY/ABSTRACT Irritability—exaggerated anger in response to non-reward—is among the most common psychiatric complaints. Because irritability in late childhood and adolescence predicts mental disorders across the lifespan, identifying the neural mechanisms involved in irritability across the transition to adolescence is paramount to intervene before youth irritability problems harden into entrenched psychiatric disorders in later adolescence and adulthood. Irritability is linked with abnormalities in reward processing, which may lead to greater frustration when rewards are not received. Such reward processing vulnerabilities may be ameliorated by better inhibitory control, which normatively increases with maturation. However, the interplay between reward processing and inhibitory control in irritability is unknown. Investigating longitudinal changes in neural circuitry is important because reward- and inhibition-related neural networks undergo substantial change from childhood through adolescence. Our overall goal is to identify reward- and inhibition-related neural pathways that characterize changes in irritability over the transition to adolescence. To this end, the proposal leverages data from the Adolescent Brain Cognitive Development (ABCD) Study, a large, national longitudinal sample of preadolescents assessed annually (N=~8,312 with usable datasets; baseline age=9-10; 1-Year Follow-Up [1-YRFU] age=10-11; 2-YRFU age=11-12). At baseline and 2-YRFU, youth complete monetary incentive delay and stop-signal tasks during fMRI acquisition that assess neural responses to reward and inhibitory control, respectively. Across all waves, youth irritability and co-occurring psychopathology are assessed using clinical interviews and parent- and youth-report measures, and multiple behavioral and parent- and youth-reported measures of youth reward processing and inhibitory control are collected. Our central hypothesis is that preadolescents with both reward- and inhibition-related neural deficits are more likely to show persistently high or increasing irritability across the transition to adolescence, whereas preadolescents with reward-related brain deficits, but better inhibition, will demonstrate decreases in irritability. Specific aims are to identify (1) separate and (2) interactive contributions of reward- and inhibition-related neural function to concurrent irritability; to identify (3a) preadolescent reward- and inhibition-related neural predictors and (3b) developmental changes in reward and inhibition neural mechanisms, of irritability trajectories and future psychopathology across the transition to adolescence; and to explore (4) the moderating role of developmental-biological-contextual factors (sex, puberty, race/ethnicity, SES, familial characteristics) on these brain-behavior relationships. This proposal will advance the field by revealing the neural circuitry of irritability. Innovative aspects include focusing on a key age range (transition to adolescence) to prevent adult disorders, multiple time point imaging, formulation of a novel and comprehensive reward-based model of irritability, machine learning methodology, and replication analyses. Our project is significant because it will be a catalyst for a research program to inform precision medicine for irritability.


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 = $323,843 )
2025	2025	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Mental Health Research Grants	000	5	12/13/2024	NON-COMPETING CONTINUATION	$323,843
														Subtotal = $323,843

Issue Date FY: 2024 ( Subtotal = $381,190 )
2024	2024	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Mental Health Research Grants	001	4	7/5/2024	NON-COMPETING CONTINUATION	$38,119
2024	2024	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR MC1947	SAN DIEGO	CA	92182	SAN DIEGO	USA	Mental Health Research Grants	000	4	12/15/2023	NON-COMPETING CONTINUATION	$343,071
														Subtotal = $381,190

Issue Date FY: 2023 ( Subtotal = $375,934 )
2023	2023	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR MC1947	SAN DIEGO	CA	92182	SAN DIEGO	USA	Mental Health Research Grants	000	3	12/22/2022	NON-COMPETING CONTINUATION	$338,340
2023	2023	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR MC1947	SAN DIEGO	CA	92182	SAN DIEGO	USA	Mental Health Research Grants	001	3	2/27/2023	NON-COMPETING CONTINUATION	$37,594
														Subtotal = $375,934

Issue Date FY: 2022 ( Subtotal = $376,094 )
2022	2022	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR MC1947	SAN DIEGO	CA	92182	SAN DIEGO	USA	Mental Health Research Grants	000	2	1/11/2022	NON-COMPETING CONTINUATION	$338,483
2022	2022	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR MC1947	SAN DIEGO	CA	92182	SAN DIEGO	USA	Mental Health Research Grants	001	2	6/6/2022	NON-COMPETING CONTINUATION	$37,611
														Subtotal = $376,094

Issue Date FY: 2021 ( Subtotal = $388,505 )
2021	2021	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR MC1947	SAN DIEGO	CA	92182	SAN DIEGO	USA	Mental Health Research Grants	000	1	3/3/2021	NEW	$388,505
														Subtotal = $388,505

Grand Total All Awards = $1,845,566

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Neural mechanisms of risk for irritability across the transition to adolescence

Award Number: R01MH122487

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/03/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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