Editorial: Baby Steps on Challenging Ground: Understanding How Early-Life Irritability Impacts Mental Health Outcomes

Irritability is increasingly recognized as an important phenotype in early life. Since Chess and Thomas’ groundbreaking longitudinal work on infants with “difficult” temperament,¹ conceptualizations of early irritability have grown and matured in the literature. Today, multiple measures of early irritability are available with a focus on dispositional anger, frustration, and negative reactivity. Additionally, investigators have mapped the normative developmental trajectory of irritability, which features a peak in temper tantrums in early childhood.² This latter phenomenon creates an interesting challenge for research interrogating the clinical relevance of early irritability for later mental health in youth. How do we ascertain what is clinically meaningful in early life against the backdrop of wide individual and developmental variation in irritability?

In this issue of the Journal, Finlay-Jones et al.³ present a timely review and meta-analysis of early irritability from ages 0 to 5 as a predictor of later internalizing and externalizing problems in youth. Internalizing refers to behaviors focused inward, such as anxiety and depression symptoms; externalizing refers to behaviors focused outward, such as disruptive behavior and aggression. The authors performed a comprehensive search of the literature from 2000 to 2021, identifying just under 100 studies on this topic and including 70 of these in their quantitative meta-analysis (collectively representing more than 830,000 children). Overall, the authors found small associations between infant irritability and later internalizing and externalizing outcomes and small-to-moderate associations between toddler/preschool irritability and later internalizing and externalizing outcomes. Thus, early irritability was a broad, consistent, and convincing predictor of later mental health problems in youth, though not an especially strong one. These results complement a prior meta-analysis of chronic irritability in older youth and associations with adult anxiety and unipolar depression.⁴ Finlay-Jones et al.³ went on to conduct thoughtful sensitivity analyses, and their article presents a thorough discussion of open questions and issues in this research area.

Here, I underscore 2 points for further consideration: measurement and mechanism. With respect to measurement, in the sensitivity analyses, interview-based assessments of early chronic irritability were shown to have the strongest associations with outcomes, relative to caregiver questionnaires or laboratory observations of behavior. That is, how early irritability was measured mattered. This finding is crucial. Remarkably, 41 distinct ways of measuring early irritability were revealed across the 70 studies. These differences derive from many sources. For one, developmental progression from infancy through early childhood necessitates that assessments be tuned to differing developmental levels.

Perhaps more tacitly, early irritability is a research area in which different theoretical frameworks converge, and the diversity of measures reflects this diversity in ancestry and interest. In the sensitivity analyses, several interview-based assessments that showed strong predictions come from the clinical framework, conceptualizing irritability as a symptom assessed in the context of diagnostic categories.⁵ (Of course, this introduces potential for tautology in measurement between baseline and later psychopathology; Finlay-Jones et al.³ showed that predictions for early irritability generally held in the handful of studies that controlled for baseline psychopathology.) More to the point, irritability is embedded as clinically relevant in this framework. This contrasts with measures that originate in developmental contexts concerned with normative variation in behavior. Here, early irritability is less differentiated from related constructs (eg, negative emotionality) in the conceptualization of temperament.⁶ Not surprisingly therefore, developmental questionnaires and laboratory tasks showed relatively weaker predictions in the sensitivity analyses.

To be sure, theoretical tension in how we think about early irritability is healthy and can be constructive for the field. At the same time, if one long-term aim is better identification of at-risk children at scale, the field must devote more attention to measurement going forward. A common definition of early irritability that integrates both clinical and developmental perspectives is a good starting place. The inclusivity and generalizability of samples also needs to broaden, as most meta-analyzed studies were conducted in the United States with predominantly non-Hispanic White participants.

As noted earlier, a second point worth underscoring is mechanism: the need to gain better purchase on how early irritability impacts mental health outcomes in youth, in terms of causal mechanisms. Studies of mediators can help clarify causal mechanisms. Mediators are typically examined as putative intervening variables that, statistically, may help explain observed associations between predictors and outcomes. In the case of early irritability, finding significant mediators will provide clues about processes that shape its links with mental health outcomes over time. Further, mediators might reflect causal factors that can be modified through prevention or early intervention, serving to improve youth outcomes. Finlay-Jones et al.³ found only 6 studies that tested mediators. Of these, the most promising initial signal was for parenting as a mediator between early irritability and externalizing outcomes. Thus, while the data attest that early irritability contributes to the emergence of a range of mental health problems, it remains unclear in what ways it does so.

Work on mechanisms is nascent and will be challenging. The modest effect sizes shown between early irritability and later mental health outcomes suggest that multiple concurrent and intervening variables play a role. For example, early irritability often co-occurs with difficulties in attention, anxiety, and other behavior and emotion dysregulation.⁷ Ideally, studies will measure related phenotypes and account for them conceptually and statistically, such as latent variable models of the structure of temperament, traits, or symptoms.⁸ As highlighted by the initial findings for parenting as a mediator, variables also interact over time at biological, behavioral, and environmental levels. For example, infants and young children with differing proneness to irritability tend to elicit differing responses from people; these responses in turn influence subsequent behavior of children. In the face of such complex processes, redoubling efforts in measurement will be key. Additionally, most current statistical tests of predictors, mediators, and moderators offer radical simplifications of natural complexity. Network analysis, including multilayer approaches, may aid in modeling multilevel interactions of variables that potentiate the emergence of mental health problems across development.⁹

In sum, Finlay-Jones et al.³ do a superb job culling the data on early irritability and youth mental health outcomes. Their review and meta-analysis document promising leads and highlight current limitations. Indeed, research on early life irritability is growing up. On one hand, we need to better reconcile its varied ancestry in the service of common definition and measurement. On the other hand, we need to take baby steps (or perhaps bounds) forward in better studying mediating mechanisms, as we admittedly walk on challenging ground.

Diversity & Inclusion Statement:

One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list.