# Neural mechanisms of risk for irritability across the transition to adolescence

> **NIH NIH R01** · SAN DIEGO STATE UNIVERSITY · 2021 · $388,505

## Abstract

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 (t...

## Key facts

- **NIH application ID:** 10119132
- **Project number:** 1R01MH122487-01A1
- **Recipient organization:** SAN DIEGO STATE UNIVERSITY
- **Principal Investigator:** LEA R DOUGHERTY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,505
- **Award type:** 1
- **Project period:** 2021-03-03 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119132

## Citation

> US National Institutes of Health, RePORTER application 10119132, Neural mechanisms of risk for irritability across the transition to adolescence (1R01MH122487-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10119132. Licensed CC0.

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