# Generating an Earlier Science of When to Worry: A Neurodevelopmental, Transactional Approach to Characterizing Irritability Patterns Beginning in Infancy

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $159,167

## Abstract

PROJECT SUMMARY: Irritability emerges during infancy as a substrate of psychopathology. However,
reliable identification of irritable infants at high risk for clinical progression is challenging, due to substantial
individual differences in adaptive or maladaptive outcomes for irritable infants over time. The When to Worry
(W2W) study utilizes a neurodevelopmental framework to generate empirically derived, parameters for
differentiation of irritability patterns that mark clinical risk. This administrative supplement request supports
completion of the 36 month clinical endpoint and imaging sub-sample assessments, delayed due to COVID-19
disruptions. Key innovations are: (1) specification of developmentally atypical patterns of irritability beginning in
infancy; (2) joint developmental consideration of irritability, executive function, and prefrontal cortical regions;
and (3) transactional focus. We first conduct a cross-sectional survey of a representative sample of 12-36 mos.
olds (N=2,000). We then ascertain an independent community cohort (N=356 infants oversampled for
irritability), with longitudinal follow-up (12-36). Irritability assessments are: (a) bimonthly parent reports and
real-time irritable vocalizations via the LENA; and (b) annual direct observations of irritability with executive
function tasks (12-36 mos.) Performance-based assessments of executive function occur annually. The 36 mo.
timepoint is the key clinical endpoint, when preschool psychopathology is well validated. Transactional
processes are assessed via parent-infant mutual regulation processes. SPECIFIC AIMS: IA. Differentiate
developmentally atypical irritability patterns from infancy-early preschool age via population-based
parameters cross-sectionally (IAi) and quantitative longitudinal parameters (IAii). IB. Specify
longitudinal parameters of irritability to optimize prediction of clinical progression. IIA-B. Map
developmentally atypical irritability patterns to disruptions in the maturation of executive function and
prefrontal cortical (PFC) regions and test the hypothesis that their joint consideration will enhance
predictive clinical utility. Prefrontal cortical maturation will be assessed from infant natural sleep-MRI at 12 &
36 months (n=50-75). We test whether atypical irritability patterns predict slowed executive function
development and abnormal PFC anatomy. IIIA-B. Elucidate how transactional processes shape clinical
prediction, testing the hypothesis that parent-infant mutual regulation processes modulate clinical
progression. Specification of irritability phenotypes in transactional context is key for prevention. The
supplement is key for completing data collection to meet critical objectives of the W2W study.

## Key facts

- **NIH application ID:** 10349344
- **Project number:** 3R01MH107652-05S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** LAUREN S WAKSCHLAG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $159,167
- **Award type:** 3
- **Project period:** 2016-03-02 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10349344

## Citation

> US National Institutes of Health, RePORTER application 10349344, Generating an Earlier Science of When to Worry: A Neurodevelopmental, Transactional Approach to Characterizing Irritability Patterns Beginning in Infancy (3R01MH107652-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10349344. Licensed CC0.

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