Irritability emerges during infancy and is a substrate of many common forms of developmental psychopathology. However, reliable identification of irritable infants at high risk for clinical progression is challenging due to high levels of normatve variation combined with substantial individual differences in adaptive or maladaptive outcomes for irritable infants over time. Building on our prior work at preschool age, the proposed study utilizes a neurodevelopmental framework to generate empirically derived, parameters for differentiation of irritability patterns that mark risk for clinical progression. Key innovations ae: (1) novel approach to specification of developmentally atypical patterns of irritability beginning n infancy; (2) joint developmental consideration of irritability, executive function, and prefrontal cortical regions; and (3) transactional focus examining the clinical import of early irritability wthin the context of parent-infant mutual (dys)regulation. To derive population-based parameters, 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=350 infants oversampled for irritability), with intensive longitudinal follow-up from 12-36 months. Focal irritability assessments are: (a) bimonthly parent reports and real-time monitoring of irritable vocalizations via the Language Environment Analysis (LENA) Pro device; and (b) annual direct observations of irritable temperament and behavior (12, 24 & 36 mos.). Performance-based assessments of executive function occur annually. Transactional processes are assessed via parental contingent responses to infant irritable vocalizations on the LENA Pro (bimonthly) and event-coded parent-infant mutual regulation processes (annually). Clinical progression is captured via latent dimensional clinical risk over time.
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 functin 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 derived estimates of anatomical properties at 12 & 36 months in an extreme group sub-sample (n=100). We test the hypothesis that atypical irritability patterns will 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 neurodevelopmental irritability phenotypes within transactional context provides a critical empirical base for targete prevention of mental disorder in its earliest prodromal phases.

Public Health Relevance

Early irritability is a precursor to most common childhood mental disorders, but identifying 'when to worry' is challenging because infants' regulatory capacities develop so rapidly. The goal of this study is to develop a scientific evidence base beginning in infancy that distinguishes the normative irritability of early childhood from atypical irritability patterns. We will use a neurodevelopmental framework to characterize typical and atypical brain and behavioral patterns longitudinally from infancy to preschool age, including how infant irritability shapes and is shaped by proximal interactions with parents, and link these to dimensional patterns of clinical risk. Generating reliable markers of irritability that identify those infants at highest risk for developmental psychopathology lays the foundation for targeted early intervention at the earliest phase of clinical risk.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH107652-02
Application #
9235325
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Friedman-Hill, Stacia
Project Start
2016-03-02
Project End
2021-02-28
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
2
Fiscal Year
2017
Total Cost
$688,581
Indirect Cost
$231,771
Name
Northwestern University at Chicago
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Roberts, Megan Y; Curtis, Philip; Estabrook, Ryne et al. (2018) Talking Tots and the Terrible Twos: Early Language and Disruptive Behavior in Toddlers. J Dev Behav Pediatr 39:709-714
Wakschlag, Lauren S; Perlman, Susan B; Blair, R James et al. (2018) The Neurodevelopmental Basis of Early Childhood Disruptive Behavior: Irritable and Callous Phenotypes as Exemplars. Am J Psychiatry 175:114-130
Mittal, Vijay A; Wakschlag, Lauren S (2017) Research domain criteria (RDoC) grows up: Strengthening neurodevelopment investigation within the RDoC framework. J Affect Disord 216:30-35